N. Araki

Calcium hydroxyapatite ceramic used as a delivery system for antibiotics

Porous blocks of calcium hydroxyapatite ceramic were evaluated as delivery systems for the sustained release of antibiotics. We tested gentamicin sulphate, cefoperazone sodium, and flomoxef sodium in powder form placed in a cylindrical cavity in calcium hydroxyapatite blocks, using in vitro studies of elution and in vivo studies in rats. Gentamicin sulphate gave a maximum concentration within the first week, which gradually decreased but was still effective at 12 weeks, when 70% of the antibiotic had been released. Even at this stage the antibiotic concentration from a 75 mg dose was five times the minimum inhibitory concentration for staphylococci. In the in vivo studies the release of gentamicin sulphate into the normal bone of rats was at similar rates and levels. The bacteriocidal activity of the drugs was not affected by packing into calcium hydroxyapatite ceramic and the blocks were completely biocompatible on histology. This new system overcomes the disadvantages of other drug delivery systems, avoiding thermal damage to the antibiotics and a second operation for the removal of the carrier. Some mechanical strength is provided by the ceramic and healing may be accelerated by bone ingrowth into its micropores.

The use of calcium hydroxyapatite ceramic in bone tumour surgery

We report 60 benign bone tumours treated by resection and curettage followed by the implantation of calcium hydroxyapatite ceramic (CHA). After follow-up of six to 60 months (average 36), no patient had local recurrence of the tumour or any adverse effects from the implants. In almost all cases radiography showed that the CHA was well-incorporated into the host bone, with new bone formation in and around the CHA. Corrective remodelling of deformed bone and normal fracture healing suggested that there was normal bone turnover in the presence of the CHA. Histology of biopsies from seven patients showed bone ingrowth into the pore structure of CHA in the central zone of some defects by one year after implantation. CHA appears to be a useful substitute for bone graft in the treatment of some benign tumours.

Calcium hydroxyapatite ceramic implants in bone tumour surgery. A long-term follow-up study.

We reviewed the results of 51 patients with benign bone tumours treated by curettage and implantation of calcium hydroxyapatite ceramic (CHA). The mean follow-up was 11.4 years (10 to 15.5). Post-operative fractures occurred in two patients and three had local recurrences; three had slightly limited movement of the adjacent joint and one had mild osteoarthritis. There were no allergic or neoplastic complications. In all cases, radiographs showed that the CHA was well incorporated into the host bone. Statistical analysis showed that absorption of the implanted CHA was greater in males (odds ratio, 6.2; 95% CI, 1.6 to 23.7) and younger patients (odds ratio, 0.6 for increase in age of 10 years; 95% CI, 0.91 to 0.99). However, the implanted CHA was not completely absorbed in any patient. We conclude that CHA is a useful and safe bone substitute for the treatment of benign bone tumours.

Prosthetic reconstruction for periacetabular malignant tumors

This article reports the reconstruction method and functional results of a newly designed tumor hip prosthesis with a constrained joint mechanism which was used after treatment for 13 primary and 5 metastatic periacetabular malignant bone tumors. The overall 5-year survival rate for patients with primary tumors (n = 13) was 50%. The local recurrence rate was 30%. More than 90% of the patients whose hips were reconstructed with the constrained tumor hip prosthesis experienced pain relief and were able to walk with a cane. No patients had greater than 3 cm shortening of the involved limb. Infection was the most serious complication. This prosthesis restored iliofemoral stability after surgical resection of periacetabular malignant tumors.

Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma

Osteosarcoma is the most prevalent bone malignant tumor in children and adolescents, and displays heterogeneous histology and high propensity for distant metastasis. Although adjuvant chemotherapy remarkably improved treatment outcome over the past few decades, prognosis for osteosarcoma patients with pulmonary metastasis is still unsatisfactory. To identify novel therapeutic targets for osteosarcoma, we investigated the gene expression profile of osteosarcomas by cDNA microarray analysis and found transactivation of receptor tyrosine kinase‐like orphan receptor 2 (ROR2) expression in the majority of osteosarcoma samples. Treatment of osteosarcoma cell lines with siRNA against ROR2 significantly inhibited cell proliferation and migration. We also identified wingless‐type MMTV integration site family, member 5B (WNT5B) as a putative ROR2 ligand and that the physiological interaction of WNT5B and ROR2 could enhance cell migration, indicating the possible roles of ROR2 and WNT5B in the metastatic property of osteosarcoma cells. Taken together, our findings revealed that the WNT5B/ROR2 signaling pathway is a promising therapeutic target for osteosarcoma. (Cancer Sci 2009; 100: 1227–1233)

Neoadjuvant chemotherapy for pediatric osteosarcoma patients

Since the first trial for chemotherapy in children with osteosarcoma in 1977, the survival rate has gradually improved. Currently, more than 60% of all patients are cured, mainly because of the introduction of intensive chemotherapy using doxorubicin, high dose methotrexate, and cisplatin. The increased survival rates have promoted efforts to improve the quality of survival through the use of limb salvage surgery rather than amputation. Improvements in chemotherapeutic efficacy should result in a more favorable outcome and better function of the affected limb. The current study evaluated factors that influence chemotherapy so that a higher survival rate could be obtained.

Frequent expression of smooth muscle markers in malignant fibrous histiocytoma of bone

Background/Aims: Malignant fibrous histiocytoma (MFH) of bone, a relatively rare primary malignant bone tumour, is a distinct clinicopathological entity as opposed to MFH derived from soft tissue. Although the true histogenesis of this condition is still controversial, a considerable number of cases of MFH in soft tissue show positive immunohistochemical reactivity for muscle markers such as desmin, common muscle actin (HHF35), and α smooth muscle actin (SMA), suggesting that MFH cells are myofibroblastic in nature. Methods: This study investigated immunoreactivity for several different muscle markers in 19 cases of MFH of bone together with reverse transcription polymerase chain reaction (RT-PCR) analysis on frozen tissue samples that were available in four cases, and compared the data with those found in 11 cases of osteosarcoma and 11 cases of soft tissue MFH treated over the same period. Results: Immunohistochemistry revealed that MFH of bone showed relatively frequent expression of smooth muscle markers, including calponin (nine cases), α-SMA (nine cases), and SM22α (18 cases), and this was confirmed by RT-PCR analysis. However, only one, two, and three cases of MFH of bone showed positive staining for desmin, MyoD1, and HHF35, respectively. Similarly, 11 osteosarcoma cases were relatively frequently positive for α-SMA (five cases), calponin (four cases), and SM22α (seven cases), and less frequently positive for desmin (one case), MyoD1 (none), and HHF35 (none). In contrast, very few MFH of soft tissue cases (n = 11) showed positive reactivity for all of these muscle markers. It has recently been reported that human bone marrow stromal cells also express various kinds of smooth muscle markers including α-SMA and calponin. Conclusions: These results suggested that MFH of bone may derive from mesenchymal stromal cells in bone marrow and has a more myofibroblastic differentiation than soft tissue MFH.

Inguinal lymphadenopathy due to metal release from a prosthesis. A case report

We report the case of a 19-year-old man with inguinal lymphadenopathy caused by metallic debris from the loosening of a prosthesis inserted after tumour resection. Large amounts of wear debris may be released from such massive replacements, and surgeons should be aware of the range of possible adverse effects.

Intramuscular haemangioma adjacent to the bone surface with periosteal reaction. Report of three cases and review of the literature.

We present three cases of intramuscular haemangioma adjacent to bone in the lower limb. All patients had local pain during the third decade. Plain radiographs showed an irregular or hypertrophic periosteal reaction on the shaft of the fibula and an intramuscular mass adjacent to the bone with inhomogeneous high signal intensity on MRI. These lesions mimic periosteal or parosteal tumours.

Intramuscular haemangioma adjacent to the bone surface with periosteal reaction

We present three cases of intramuscular haemangioma adjacent to bone in the lower limb. All patients had local pain during the third decade. Plain radiographs showed an irregular or hypertrophic periosteal reaction on the shaft of the fibula and an intramuscular mass adjacent to the bone with inhomogeneous high signal intensity on MRI. These lesions mimic periosteal or parosteal tumours.