Shunzo Osaka

Survivin as a prognostic factor for osteosarcoma patients.

Purpose: Survivin is one of the apoptosis inhibitor genes and is rarely expressed in adult tissues. However, survivin expression has been detected in various human cancers and correlations have been recognized between the level of expression of this gene in tumors and prognosis. In this study, we investigated the correlations between survivin mRNA expression in osteosarcoma tissues and clinicopathological parameters. Methods: There were 22 osteosarcoma patients in our hospital with paraffin-embedded tissues which could be extracted from biopsy specimens. We used the RT-PCR method after extracting total RNA and conducted a densitometric analysis to determine the ratio of survivin relative to h-GAPDH as an internal marker. Results: Expression of survivin mRNA was detected in all osteosarcoma samples. Patients with metastasis had high survivin mRNA levels in initial biopsy specimens (p<0.01). Moreover, there was a statistically significant difference in survivin mRNA expression between patients with and without metastasis (p<0.01). Conclusion: We concluded that high levels of survivin mRNA expression suggest poor prognosis for osteosarcoma patients.

Long-term outcome following surgical treatment of sacral chordoma.

Sixteen sacral chordoma surgeries performed at a single institution during the 1983–2008 period were retrospectively studied. Our aim is to assess surgical treatment and long‐term outcomes.

Analysis of limb function after various reconstruction methods according to tumor location following resection of pediatric malignant bone tumors

BackgroundIn the reconstruction of the affected limb in pediatric malignant bone tumors, since the loss of joint function affects limb-length discrepancy expected in the future, reconstruction methods that not only maximally preserve the joint function but also maintain good limb function are necessary. We analysis limb function of reconstruction methods by tumor location following resection of pediatric malignant bone tumors.Patients and methodsWe classified the tumors according to their location into 3 types by preoperative MRI, and evaluated reconstruction methods after wide resection, paying attention to whether the joint function could be preserved. The mean age of the patients was 10.6 years, Osteosarcoma was observed in 26 patients, Ewings sarcoma in 3, and PNET(primitive neuroectodermal tumor) and chondrosarcoma (grade 1) in 1 each.ResultsType I were those located in the diaphysis, and reconstruction was performed using a vascularized fibular graft(vascularized fibular graft). Type 2 were those located in contact with the epiphyseal line or within 1 cm from this line, and VFG was performed in 1, and distraction osteogenesis in 1. Type III were those extending from the diaphysis to the epiphysis beyond the epiphyseal line, and a Growing Kotz was mainly used in 10 patients. The mean functional assessment score was the highest for Type I (96%: n = 4) according to the type and for VFG (99%) according to the reconstruction method.ConclusionThe final functional results were the most satisfactory for Types I and II according to tumor location. Biological reconstruction such as VFG and distraction osteogenesis without a prosthesis are so high score in the MSTS rating system. Therefore, considering the function of the affected limb, a limb reconstruction method allowing the maximal preservation of joint function should be selected after careful evaluation of the effects of chemotherapy and the location of the tumor.

Surgical management of malignant soft tissue tumours in patients aged 65 years or older

Objective. With the aim to determine the most effective treatment for primary malignant musculoskeletal tumours in patients aged 65 years or older, we reviewed cases of low- and high-grade neoplasms, surgical margins, surgical methods, and the prognoses of elderly and aged patients at our institution. Methods. Records of 25 patients aged 65 years or older who had malignant soft tissue tumours from December 1986 to February 1997 were reviewed. Low- and high-grade neoplasms accounted for 8 and 17 patients, respectively. 11 patients were aged 65 to 69 years, while 14 were 70 years or older. Surgical margins were wide in 19 cases, marginal in 4, and intralesional in 2. Reconstruction was done using 6 musculocutaneous flaps and/or 4 vessel grafts. As adjuvant therapy, radiotherapy was used in 5 cases and chemotherapy in 3. There was no recurrence in patients with wide surgical margins (determined on the basis of gross inspection of the excised tumour and the cut surface); but there was recurrence in 4 patients with marginal margins, and one patient with intralesional margin. Two patients with intralesional, 4 with marginal, and 2 with wide margins, died from recurrence at the primary site and metastasis, or from metastasis without recurrence at the primary site. Results. Follow-up periods ranged from 4 months to 180 months (mean, 91.6 months). The overall 5-year survival rate was 79.6%; for low- and high-grade neoplasms, the figures were 100% and 69.7%, respectively; for those aged 65 to 69 years and in their 70s or older, the figures were 90.9% and 70.1%, respectively. Conclusion. For geriatric patients, wide surgical margins are required to manage both low- and high-grade neoplasms, in order to avoid multiple surgeries.

Reconstruction of the knee extensor mechanism in patients with a malignant bone tumor of the proximal tibia

PurposeReconstruction of the knee extensor mechanism after the excision of a malignant bone tumor is often difficult, particularly if the tumor is located in the proximal tibia. We developed a novel method to reconstruct the knee extensor mechanism using autologous fasciae, and subsequently evaluated the efficacy of this method.MethodsWe examined the studied reconstruction method, range of motion, extension lag, knee extensor strength, and functional evaluation of three patients with a malignant bone tumor in the proximal tibia. All three patients underwent reconstruction of the knee extensor mechanism by our method.ResultsAll patients experienced satisfactory outcomes with regard to the above-mentioned parameters. The functional evaluation scores in the three patients were 90%, 95%, and 95% (mean, 90%).ConclusionIn this analysis of our recently devised reconstruction method, the follow-up duration was short and only three patients were investigated. However, if appropriate patients are carefully selected for this procedure, long-term outcomes associated with new technique may be better than those associated with other methods of the knee extensor reconstruction.

Clinical experience of novel interconnected porous hydroxyapatite ceramics for the revision of tumor prosthesis: a case report

BackgroundAs for being cautious with tumor prostheses, revision of uncemented tumor prostheses in particular, it is necessary to remove cortical bone from the stem circumference with a chisel when the stem is extracted. This assures that bone in-growth will occur within the stem in itself. As a result, re-substitution of mass autogenous bone graft round a new stem is subsequently necessary. When rivision of uncemented tumor prosthesis of distal femur was performed, we evade fibula transplant by transplanting interconnected porous hydroxyapatite ceramic (IP-CA: Neobone) with a self bone, and reports its experience with the case that acquired enough strength.Case reportIn this report, we present the case of a 27-year-old female with stem breakage of tumor prosthesis and do revision surgery for prosthetic failure. In the case of revision surgery, autologous bone and Neobone were mixed, and this was transplanted to stem circumference. The Radiological Evaluation System of the ISOLS showed excellent results for all items. She can walk without using a cane or orthosis, and the score of the MSTS is 80%.ConclusionWhen revision of uncemented tumor prostheses of the distal femur was performed, we avoided fibula graft by using Neobone with the patients own bone tissue. Our experience with this case may indicate that adequate strength is achieved.

Interleukin-8 Producing Malignant Fibrous Histiocytoma with Prolonged Fever

We present a case of malignant fibrous histiocytoma accompanied by prolonged spiking fevers, which disappeared after tumor resection. Sarcoma with fever as a primary symptom is rare. Furthermore, in this case, fever was closely related to the clinical course of the tumor. In order to detect possible production of febriferous substance(s), we used blood and tumor tissue samples to investigate nine candidate cytokines possibly responsible for the fever. Expression of IL-8 mRNA was detected in preoperative peripheral blood mononuclear cells by RT-PCR. Expressions of IL-6, IL-8, IFN-γ and TNF-α mRNAs were also detected in tumor tissue, while IL-1α, IL-1β, IL-2, IL-4 and COX-2 mRNAs were not. We suspected IL-8 to be a causative factor, and examined its localization by immunohistochemical staining, paraffin sections of tumor tissue stained positive for IL-8. Since infiltrating mononuclear cells were positive for IL-8, this may explain the tumor-associated fever. This case involves intratumoral production of IL-8 as a causative factor, and IL-6, IL-8, IFN-γ and TNF-α cytokine production might have resulted from stimulation with a substance(s) derived from tumor tissue, since the fever disappeared postoperatively. To date the patient is alive and in good health for 7 years and 2 months since the surgery.

Experience with extendable prostheses for malignant bone tumors in children

BACKGROUND/PURPOSE In limb reconstruction following resection of malignant bone tumors in children, extendable prostheses are considered to be useful since future leg length correction can be controlled. We evaluated the usefulness of extendable prostheses in 11 such cases. METHODS The study included 11 children aged 7-16 years (mean 11 years) who underwent limb reconstruction using an extendable prosthesis between 1994 and 2008. The follow-up period varied from 1 to 16 years (mean 6 years and 2 months). Nine patients had osteosarcoma, one had a primitive neuroectodermal tumor (PNET) and one had Ewings sarcoma. The tumor was located in the distal femur, (n = 6), proximal femur (n = 1), or proximal tibia (n = 4). Functional scores, X-ray images, the number of lengthening procedures, total length gain, complications, and leg length discrepancy were recorded for each patient. RESULTS The functional scores range from 52% to 96% (mean 84%). X-Ray evaluation revealed fair and poor bone remodeling in three patients each. The mean number of elongation procedures was 2.8 and the mean total length gain was 49.7 mm. The final leg length discrepancy was 29.2 mm. CONCLUSION Extendable bone prostheses are useful for reconstruction. According to our experience, this method is indicated in children of at least 10 years of age for whom a future leg-length discrepancy of up to 4 cm is expected and who have a lesion located in the distal femur where the prosthesis can be adequately covered by soft tissue.

Chondrosarcoma with Myxoid Change: A Study Using a Quick-freezing and Deep-etching Method

A middle-aged Japanese woman visited the Orthopedics Department of Nihon University Nerima Hikarigaoka Hospital complaining of pain in the left hip joint that had started approximately 8 months earlier. Following several examinations, including imaging diagnoses, an incisional biopsy demonstrated a malignant acetabular bone tumor, which was removed and examined by a quick-freezing and deep-etching (QF–DE) method, conventional electron microscopy, and light microscopy. Histologically, the tumor was a chondrosarcoma with marked myxoid changes. An interesting extracellular matrix was observed by the QF–DE method. The myxoid area consisted of a fine meshwork of proteoglycans (PG) without obvious aggrecans, which resembled that of PG usually present in the pericellular matrix of normal cartilage. Thin collagen fibrils with pleated surface structures of regular periodicity were also seen, which were sparsely distributed in wide areas except for the pericellular matrix. These collagen fibrils were of the type that are mainly located in the pericellular side of the territorial matrix in normal cartilage. A myxoid matrix consisting of thin collagen fibrils on the background of pericellular type PG suggested that the myxoid matrix in the chondrosarcoma resembled those of the pericellular and pericellular sides of the territorial matrices in normal cartilage.

Extraskeletal myxoid chondrosarcoma: a study using a quick-freezing and deep-etching method

A case of extraskeletal myxoid chondrosarcoma (ESMC), which developed in the right thigh of a middle-aged Japanese woman, was studied using immunohistochemistry, conventional electron microscopy, and the quick-freezing and deep-etching (QF-DE) method. In addition to typical light microscopic findings of ESMC, conventional electron microscopy indicated that the tumor cells had features of chondrocytes. Immunohistochemically, the tumor cells showed a positive immunoreaction for S100 protein. A diagnosis of ESMC was made. An interesting observation was the ultrastructural features of collagen fibrils in the myxoid matrix highlighted by the QF-DE method. These collagen fibrils consisted of relatively thin collagen (20–35 nm) with pleated surface structures. The surface striation at 65 nm was obscure. We consider that such a finding of collagen fibrils identified by the QF-DE method is one of the characteristics of the myxoid matrix of ESMC, and this is useful for the differential diagnosis of myxoid soft tissue tumors.