Long-term outcome following surgical treatment of sacral chordoma.

BACKGROUND: 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. METHODS: Fifteen patients underwent primary wide excision, and one intralesional excision using ethanol for local control and radiation therapy (RT). A combined anteroposterior approach for large tumors above S2, and wide excision was performed with the modified threadwire-saw (MT-saw) after 1997. RESULTS: Fourteen of the 15 patients had wide margins, one a wide margin with contamination. The MT-saw was facilitated sacral excision with wide margins. Eleven patients are alive for 5-28 years. Five patients died before 10 years, two patients experienced sepsis, and one of another disease. Two patients died of local recurrence (LR) and another of multiple metastases after intralesional excision and wide excision with contamination, respectively. LR and complications occurred 4 each of 11 patients with tumors ≥ 10 cm, neither with tumors < 10 cm. The overall 5- and 10-year survival rate with wide surgical margins was 13/16 (81.3%) and 8/13 (61.5%). CONCLUSIONS: A combined anteroposterior approach for large tumors, and the MT-saw facilitates sacral excision with wide margins. Wide excision is recommended for younger patients.

Inhibition of human osteosarcoma cell migration and invasion by a gene silencer, pyrrole-imidazole polyamide, targeted at the human MMP9 NF-κB binding site.

Osteosarcoma is one of the most prevalent bone tumors, occurring mostly in adolescence. However, no noticeable progress has been achieved in developing new therapeutic agents for this disease. Matrix metalloproteinase 9 (MMP9), a type IV collagenase, is a known anticancer target and is overexpressed in osteosarcomas. MMPs can degrade components of the extracellular matrix and are known to be involved in tumor invasion and metastasis. In the present study, we designed and synthesized a pyrrole-imidazole polyamide (HN.49), a gene-silencing agent that specifically targets the nuclear factor-kappa B (NF-κB) binding site of the human MMP9 promoter. We then examined the effect of HN.49 on the enzyme activity of MMP9 and the migration activity of osteosarcoma cells in vitro. It was clearly shown that HN.49 polyamide reduced the expression level of MMP9 mRNA and the enzymatic activity of MMP-9 in SaOS-2 cells. Moreover, HN.49 polyamide inhibited migration and invasion by SaOS-2 cells in in vitro wound-closure and matrigel-invasion assays. These results indicate that HN.49 may be a potential therapeutic agent for inhibiting the invasion and metastasis of osteosarcoma.

Giant-cell tumor of the patella.

We report a 38-year old man with a giant-cell tumor in a rare site, the patella. Primary patellar neoplasms are highly unusual. According to a survey by the Bone and Soft Tissue Tumor Committee of the Japanese Orthopaedic Association, of more than 2,126 giant-cell tumors of bone reported since 1972, only 22 were primary patellar neoplasms. We present a case of this rare entity along with its clinical and radiographic features. The first clinical symptom was anterior knee pain. Though anterior knee pain has numerous and varied causes, it is necessary to consider patellar bone tumors in the differential diagnosis.

Revision of tumor prosthesis of the knee joint.

BACKGROUND: Among 40 patients with primary malignant tumors of the knee joint who underwent reconstruction of the affected limb with tumor prosthesis, revision was required in 7 due to stem breakage or loosening. SUBJECTS AND METHODS: In the 7 cases undergoing revision, conditions and background factors at the time of breakage, the breakage site, time of revision, models of previous and new prostheses, stem diameters before and after revision, details of the revision (blood loss, operative time), and the presence or absence of adjuvant therapy were determined. RESULTS: The replacement site was the distal femur in 5 and proximal tibia in 2. Revision was performed 6 years and 2 months after the previous prosthesis placement on average. The broken prosthesis model was KMFTR in 4 and HMRS and the physio-hinge type in one each. Revision due to loosening was performed in a case requiring replacement with Growing Kotz prosthesis. The model was switched to HMRS in 3, and the stem diameter was changed to 12 mm in 3 KMFTR breakage cases. The mean stem diameters were 11.2 and 10.2 mm in the non-revision and revision groups. The respective resection rates were 36 and 45%. The mean functional evaluation was 70.1% before and 76.2% after revision. CONCLUSION: To reduce the risk of tumor prosthesis breakage, the amount of bone resection should be limited to 30% or less in the affected bone, the stem diameter should be at least 12 mm, and the stem shape should be fitted to the anatomical shape of the femur.

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 Ewing's 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.

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

BACKGROUND: In 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 METHODS: We 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, Ewing's sarcoma in 3, and PNET(primitive neuroectodermal tumor) and chondrosarcoma (grade 1) in 1 each. RESULTS: Type 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. CONCLUSION: The 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.

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

PURPOSE: Reconstruction 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. METHODS: We 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. RESULTS: All 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%). CONCLUSION: In 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.

BACKGROUND: As 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 REPORT: In 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%. CONCLUSION: When revision of uncemented tumor prostheses of the distal femur was performed, we avoided fibula graft by using Neobone with the patient's own bone tissue. Our experience with this case may indicate that adequate strength is achieved.

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.

A comparative study for wide excision of malignant tumors distal to S2.

BACKGROUND AND AIM: We conducted a retrospective study comparing 5 patients (Group A) who underwent posterior excision of tumors distal to S2 using a modified threadwire saw (MT-saw) with 5 similar patients (Group B) who underwent tumor excision using chisels and airtomes. PATIENTS AND METHODS: The data of 10 patients were obtained from intra-operative records. A flexible silver guide probe connected to an MT-saw by a suture thread was devised for use in osteotomy passing through the S1 sacral canal in the lateral sacrum. Operative time, blood loss and excisional margins were compared between the two groups. RESULTS: Group A had a shorter average operative time (2 hours 24 minutes) and smaller average blood loss (2,124.6 ml) than Group B. In Group A, one patient incurred an S1 nerve root injury, and all patients had wide histological margins. In Group B, one patient had an S1 nerve root injury and another tumor contamination due to a fracture. CONCLUSION: The MT-saw greatly facilitated lateral sacral osteotomy and reduced the risk of tumor cell spread, permitting faster, safer excision with a wider margin.

Survivin expression levels as independent predictors of survival for osteosarcoma patients.

Survivin expression has been detected in various cancers and correlations have been recognized between the level of expression of this gene in tumors and prognosis. However, the aforementioned authors did not evaluate correlations between prognosis and survivin expression levels using surgically resected samples. In this study, we retrospectively investigated outcomes by examining the correlations between expression of this gene and clinicopathological parameters. Biopsy and resected specimens from which paraffin-embedded tissues could be extracted, were available from 16 patients in our hospital. We used the RT-PCR method and conducted a densitometric analysis to determine the ratio of survivin relative to h-GAPDH as an internal marker. Expression of survivin mRNA was detected in all samples. There was a significant negative correlation between survivin expression levels and duration of follow up, in months, using the Spearman's rank for the initial biopsy samples (rho=-0.775, p<0.01) and those obtained after chemotherapy (rho=-0.687, p<0.01). Moreover, Cox multivariate regression identified the survivin expression levels in both biopsy and post-chemotherapy samples as independent predictors of survival. We conclude that survivin levels in both initial biopsy and post-chemotherapy samples are useful prognostic indicators.

Rembrandt's Maria Bockenolle has a butterfly rash and digital deformities: overlapping syndrome of rheumatoid arthritis and systemic lupus erythematosus.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are the most common autoimmune disorders, although they each have very different pathophysiology. In general, RA is considered to be a Th1-mediated disease, while SLE is a Th2-mediated disease. Thus, their overlapping, in so called "rhupus", is a rare condition. In Rembrandt van Rijn's (1606-1669) portrait of the middle-aged Maria Bockenolle, we have what may be the earliest depiction of a case of rhupus syndrome: the coexistence of a butterfly rash and digital deformities. This suggests the possible historical importance of an RA epidemic which took place in the early 17th century.

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.

Clinical significance of a wide excision policy for sacrococcygeal chordoma.

PURPOSE: Surgical treatment of sacrococcygeal chordoma is very difficult and the recurrence rate is high. We investigated the outcomes of wide excision in 12 sacrococcygeal chordoma patients treated between 1983 and 2003. METHODS: The 12 patients underwent primary wide excision. The conventional procedure was wide excision employing a chisel and airtome for sacral tumours, and in 1997 a new threadwire saw procedure was introduced. All 12 patients were included in a retrospective analysis of tumour- and treatment-related variables, and outcomes. RESULTS: Six patients underwent surgery with a combined anterior-posterior approach at the cephalad sacral border. In 12 patients, 11 lesions were broadly excised, and in the 1 remaining patient the intralesional margin showed tumour contamination due to a fracture macroscopically. The latter patient received post-operative radiation therapy, but suffered a recurrence 8.0 years later. Three patients died before final follow-up: one from subsequent metastases, two elderly patients from complications. For the 10 chordoma patients, i.e. excluding the two who died due to complications, the 5, 10 and 20 years recurrence rates were 100, 66.7 and 66.7%, respectively. For the 12 patients, overall 5, 10 and 20 years survival rates were 83.3, 55.6 and 55.6%, respectively. CONCLUSIONS: Our results suggest that large chordoma should be widely excised, using a modified threadwire saw, with a combination of anterior-posterior procedures.

Correlation between the histological grade of chondrosarcoma and the expression of MMPs, ADAMTSs and TIMPs.

BACKGROUND: The malignant degree of human chondrosarcoma can be difficult to determine using only histological findings. We, therefore, assessed the expression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase (ADAM) with thrombospondin motifs (ADAMTSs) and tissue inhibitor of metalloproteinases (TIMPs) in chondrosarcoma and ascertained the relationships to histological degree of malignancy and prognosis. MATERIALS AND METHODS: In 28 chondrosarcoma cases, immunostaining was performed using antibodies against MMP 2, 3, 7, 9, 13, ADAMTS 4, 5 and TIMP 1, 2, 3. RESULTS: The chondrosarcoma were classified into groups of 7, 15 and 6 cases based on histologically malignant grade I, II and III, respectively. All target proteins were expressed in chondrosarcoma. Positive correlations (p < 0.05) existed between immunostaining scores and histological grades for all proteins except MMP 9, with strong correlations (p < 0.01) for MMPs 2, 3 and 13, both ADAMTSs and all 3 TIMPs. No correlation existed between prognosis and immunostaining scores. CONCLUSION: These target proteins could, thus, indicate the degree of malignancy in human chondrosarcoma.

Longitudinal osteotomy of lateral sacrum for malignant iliac tumor using modified threadwire saw.

A longitudinal osteotomy of lateral sacrum for malignant iliac tumors using modified threadwire saw is conducted. This procedure issignificantly wide, rapid and safe.

Radical excision of malignant sacral tumors using a modified threadwire saw.

BACKGROUND: Surgical treatment of malignant sacral tumors is difficult, and has a high rate of recurrence. OBJECTIVES: The aim of this study was to examine the wide margin of large and small malignant sacral tumors using a threadwire saw (T-saw). MATERIALS AND METHODS: We devised a flexible silver guide probe connected to a modified threadwire saw by a suture thread to perform osteotomies. We operated on 10 patients with sacral tumors using this device. The sacral excisions were performed via a posterior approach by four surgeons (two on each side) working simultaneously. RESULTS: We obtained a wide margin in all cases and no recurrence, after a mean follow-up of 4 years 2 months (range, 1 year 8 months-7 years 8 months). In one case, one nerve root on the right side was injured. CONCLUSIONS: Our new method is easier and faster than the conventional method in cases in which bilateral sacral nerve root canals require sectioning, and it produces a wide tumor margin.

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-gamma and TNF-alpha mRNAs were also detected in tumor tissue, while IL-1alpha, IL-1beta, 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-gamma and TNF-alpha 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.

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.