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Purpose The role of chemotherapy (CT) and radiotherapy (RT) for management of extraskeletal osteosarcoma (ESOS) remains controversial. We examined disease outcomes for ESOS patients and investigated the association between CT/RT with recurrence and survival. Patients and methods Retrospective review at 25 international sarcoma centers identified patients ≥18 years old treated for ESOS from 1971 to 2016. Patient/tumour characteristics, treatment, local/systemic recurrence, and survival data were collected. Kaplan–Meier survival and Cox proportional-hazards regression and cumulative incidence competing risks analysis were performed. Results 370 patients with localized ESOS treated definitively with surgery presented with mainly deep tumours (n = 294, 80%). 122 patients underwent surgical resection alone, 96 (26%) also received CT, 70 (19%) RT and 82 (22%) both adjuvants. Five-year survival for patients with localized ESOS was 56% (95% CI 51%–62%). Almost half of patients (n = 173, 47%) developed recurrence: local 9% (35/370), distant 28% (102/370) or both 10% (36/370). Considering death as a competing event, there was no significant difference in cumulative incidence of local or systemic recurrence between patients who received CT, RT, both or neither (local p = 0.50, systemic p = 0.69). Multiple regression Cox analysis showed a significant association between RT and decreased local recurrence (HR 0.46 [95% CI 0.26–0.80], p = 0.01). Conclusion Although the use of RT significantly decreased local recurrences, CT did not decrease the risk of systemic recurrence, and neither CT, nor RT nor both were associated with improved survival in patients with localized ESOS. Our results do not support the use of CT; however, adjuvant RT demonstrates benefit in patients with locally resectable ESOS.

Osteosarcoma (OS) is a highly malignant bone tumor and the prognosis for non‐responders to chemotherapy remains poor. Previous studies have shown that human sarcomas contain sarcoma‐initiating cells (SIC), which have the characteristics of high tumorigenesis and resistance to chemotherapy. In the present study, we characterized SIC of a novel OS cell line, screened for SIC‐related genes, and tried to regulate the proliferation of OS by metabolic interference. Initially, we established a new human OS cell line (OS13) and isolated clones showing higher tumorigenesis as SIC (OSHIGH) and counterpart clones. OSHIGH cells showed chemoresistance and their metabolism highly depended on aerobic glycolysis and suppressed oxidative phosphorylation. Using RNA‐sequencing, we identified LIN28B as a SIC‐related gene highly expressed in OSHIGH cells. mRNA of LIN28B was expressed in sarcoma cell lines including OS13, but its expression was not detectable in normal organs other than the testis and placenta. LIN28B protein was also detected in various sarcoma tissues. Knockdown of LIN28B in OS13 cells reduced tumorigenesis, decreased chemoresistance, and reversed oxidative phosphorylation function. Combination therapy consisting of a glycolysis inhibitor and low‐dose chemotherapy had antitumor effects. In conclusion, manipulation of glycolysis combined with chemotherapy might be a good adjuvant treatment for OS. Development of immunotherapy targeting LIN28B, a so‐called cancer/testis antigen, might be a good approach., Osteosarcoma‐initiating cell antigen LIN28B was expressed in sarcoma tissues. ES, epithelioid sarcoma; MFS, myxofibrosarcoma; OS, osteosarcoma; SS, synovial sarcoma.

AimsThe aims of this study were to analyse the long-term outcome of vascularised fibular graft (VFG) reconstruction after tumour resection and to evaluate the usefulness of the method.Patients and MethodsWe retrospectively reviewed 49 patients who had undergone resection of a sarcoma and reconstruction using a VFG between 1988 and 2015. Their mean follow-up was 98 months (5 to 317). Reconstruction was with an osteochondral graft (n = 13), intercalary graft (n = 12), inlay graft (n = 4), or resection arthrodesis (n = 20). We analysed the oncological and functional outcome, and the rate of bony union and complications.ResultsFive- and ten-year overall survival rates were 89% and 86%, respectively. Local recurrence occurred in two patients. Eight patients developed pulmonary metastases. Bone union was achieved in 44 patients (90%). Fracture occurred in six patients (12%), infection in three (6%), and nonunion in five (10%). The mean Musculoskeletal Tumor Society (MSTS) scores were as follows: osteochondral graft 70%; intercalary graft 73%; inlay graft 89%; and resection arthrodesis 83%.ConclusionAlthough associated with a relatively high rate of complications, each reconstruction method is useful, with a high rate of successful limb salvage and a good long-term functional outcome. Cite this article: Bone Joint J 2017;99-B:1237–43.

Purpose: A clinical feature of myxofibrosarcoma is local recurrence, but knowledge about distant metastasis is sparse. We evaluated the tendency of clinical and histological features of metastasis in myxofibrosarcoma patients. Methods: Fifty-eight patients with myxofibrosarcoma were treated in our hospitals, and a total of 16 consecutive patients with distant metastases were included in this retrospective study (9 males and 7 females, with a mean age of 77 years). Because there was no patient complicated by both lung and lymph node metastases, we compared the age, sex, tumor size and location, French Federation of Cancer Centers Sarcoma Group (FNCLCC) grade, American Joint Committee on Cancer (AJCC) stage, and times of the first metastasis from the initial examination between the lung and lymph node groups. In addition, we examined factors affecting the prognosis. Results: The median follow-up period was 42.9 months (range 8–142). Eleven of 16 patients developed pulmonary metastases. The sites of extra pulmonary metastases were the lymph nodes in 5 patients, bone in 1, subcutaneous in 1, intramuscular in 1, and peritoneum in 1. The median time for patients to develop distant metastases was 17.4 months (range 0–59). The time until the onset of the first metastasis in the lung metastasis group was significantly shorter than in the lymph node group (p

Purpose To evaluate the results of carbon ion radiation therapy administered to 188 patients with unresectable primary sacral chordomas. Patients and methods One hundred eighty-eight patients were treated with carbon ion radiation therapy at a single institute between 1996 and 2013 and retrospectively analyzed. The median age was 66 years. The highest proximal invasion reached past S2 level in 137 patients. The median clinical target volume was 345 cm(3). One hundred six patients received 67.2 gray equivalents (GyE)/16 fractions (fr), 74 patients received 70.4 GyE/16 fr, 7 patients received 73.6 GyE/16 fr, and 1 patient received 64.0 GyE/16 fr. Results The median follow-up period was 62 months (range, 6.8-147.5 months). Seventy percent of patients were followed for 5 years or until death. The 5-year local control, overall survival, and disease-free survival rates were 77.2%, 81.1%, and 50.3%, respectively. Forty-one patients had a local recurrence. Sex, tumor volume, level of proximal invasion, and irradiated dose were unrelated to local control. There was grade 3 toxicity of the peripheral nerves in 6 patients and grade 4 toxicity of the skin in 2 patients. Ambulation remained in 97% of patients. Conclusions Carbon ion radiation therapy was safe and effective for unresectable chordoma and provided good local control and survival while preserving ambulation.

The objective of this study was to investigate the association between ligamentum teres injury and the hip joint cartilage damage pattern in patients with femoroacetabular impingement.We compared articular cartilage damage between ligamentum teres-intact and-ruptured hips. Data were collected for 77 consecutive patients with femoroacetabular impingement who underwent hip arthroscopy. The locations of the chondral lesions were recorded on anatomic articular maps using the geographic zone method. The patients were divided into 2 groups (ligamentum teres-intact and-injured groups), and the incidence and degree of cartilage injury were compared between the 2 groups by use of the Mann-Whitney U test.In patients with ligamentum teres injury, chondral damage extended to the middle-inferior area of the acetabulum (7.6% [grade 1] in ligamentum teres-intact group and 66.6% [grade 1, 12.1%; grade 2, 42.4%; grade 3, 12.1%] in ligamentum teres-injured group, P.01) and the apex of the femoral head (anterior apex: 7.1% [grade 1, 3.8%; grade 2, 3.3%] in intact group and 42.4% [grade 1, 30.3%; grade 2, 12.1%] in injured group, P.01; middle apex: 7.6% [grade 1, 3.8%; grade 2, 3.8%] in intact group and 63.5% [grade 1, 42.4%; grade 2, 18.1%; grade 3, 3.0%] in injured group, P = .04; posterior apex: 7.6% [grade 1, 3.8%; grade 2, 3.8%] in intact group and 42.4% [grade 1, 30.3%; grade 2, 12.1%] in injured group, P.01).This study showed the association between ligamentum teres injury and articular cartilage damage in the inferior middle part of the acetabulum and the apex of the femoral head in patients treated for femoroacetabular impingement.Level IV, case-control study.

Chordomas are rare, low grade, malignant tumours derived from the ectopic remnants of the notochord that line the axial skeleton. They are characterised by their slow growth, long disease course and propensity for local relapse. Furthermore, up to 40% of non-cranial chordomas metastasise. We describe the first reported case of a hand metastasis arising from a conventional sacral chordoma after carbon ion radiotherapy. The common occurrence of distant metastasis with chordomas makes it important to perform a systemic examination, in part because their resection might improve patient prognosis.

Soft tissue angiofibroma (STA), a recently suggested new histologic entity, is a benign fibrovascular soft tissue tumor composed of bland spindle-shaped tumor cells with abundant collagenous to myxoid stroma and branching small vessels. The lesion has a characteristic AHRR-NCOA2 fusion gene derived from chromosomal translocation of t(5;8)(p15;q13). However, morphologically similar tumors containing abundant fibrovascular and myxoid stroma can complicate diagnosis. We designed an original DNA probe for detecting NCOA2 split signals on fluorescence in situ hybridization (FISH) and estimated its utility with 20 fibrovascular tumors: 4 each of STAs, solitary fibrous tumors (SFTs), and cellular angiofibromas and 3 each of low-grade myxofibrosarcomas, myxoid liposarcomas, and low-grade fibromyxoid sarcomas. We also performed FISH for 13q14 deletion and immunohistochemistry (IHC) staining for estrogen receptor, progesterone receptor, retinoblastoma protein, and MUC-4 expression. Furthermore, IHC for Stat6 was conducted in the 20 cases analyzed by FISH and in an additional 26 SFTs. We found moderate to strong nuclear Stat6 expression in all SFTs but no expression in the other tumors. Both estrogen receptor and progesterone receptor expressions were observed in STAs, SFTs, and cellular angiofibromas. Expression of retinoblastoma protein was found in less than 10% of cells in all tumor types except myxoid liposarcoma. The low-grade fibromyxoid sarcomas were strongly positive for MUC-4. All STAs showed NCOA2 split signals on FISH. All tumors, regardless of histologic type, had 13q14 deletion. The NCOA2 FISH technique is a practical method for confirming STA diagnosis. The combination of NCOA2 FISH and Stat6 IHC proved effective for the differential diagnosis of STA, even when using small biopsy specimens.

Giant cell tumor of the sacrum is extremely difficult to manage. Standard treatments, including surgery and radiation, are associated with significant complications and recurrence rates. In this manuscript, we report an early clinical result of a case of giant cell tumor of the sacrum successfully managed with selective arterial embolization. A 56-year-old woman underwent selective embolization for management of giant cell tumor of the sacrum. Radiologically, massive shrinkage of the extraosseous mass and increased peripheral ossification were obvious. Clinically, rapid pain relief was achieved and gait disability recovered. At final follow-up 28 months after completion of treatment, she retained normal activity in daily life. We stress the effectiveness of selective arterial embolization as a less invasive and less complicated primary treatment of giant cell tumors of the sacrum.

We undertook a prospective study to evaluate the prognostic significance of the serum levels of vascular endothelial growth factor (VEGF) in predicting the survival of patients with osteosarcoma. The levels were measured by an enzyme-linked immunosorbent assay in 15 patients with osteosarcoma before commencing treatment. The patients were divided into two groups, with a high or a low serum VEGF level, and the incidence of metastases and overall survival rate were compared. No significant relationship was observed between the serum VEGF levels and gender, age, the size of the tumour or the response to pre-operative chemotherapy. Patients with a serum VEGF > 1000 pg/ml had significantly worse survival than those with a level < 1000 pg/ml (p = 0.002). The serum VEGF level may be useful in predicting the prognosis for survival in patients with osteosarcoma.

The periosteal chondrosarcoma is an uncommon juxtacortical malignant bone tumor. Most are low-grade (grade 1), and their relatively good prognosis is emphasized even if treatment is local resection. Once periosteal chondrosarcomas recur, however, the grade of malignancy may become higher and it may be diffi cult to excise the tumor completely. Therefore, it is important to demonstrate the extent of the tumor accurately. We report a case of grade 2 periosteal chondrosarcoma of the femur and focus on tumor invasion into the underlying cortex.

Background We retrospectively reviewed 137 consecutive total hip arthroplasties performed with AML-A stems and Tri-Lock cups to see whether design modifications made to these components would achieve durable biological fixation in the Japanese population in whom developmental dysplasia of the hip (DDH) is relatively common. Patients from our initial clinical series using these components are available for more than 10 years’ follow-up. Methods Between April 1988 and June 1994, we performed 137 total hip arthroplasties using the AML-A prosthesis for the patients with osteoarthritis of the hip joint. We excluded 26 hips with less than 10 years’ follow-up and five hips from patients who died before the 10-year follow-up. The mean follow-up for the 105 remaining THAs is 155.2 months (range 120–237 months). The average age of these patients at the time of surgery was 53.1 years (range 22–81 years). Results In total, 17 THAs required component revisions. In seven cases, the first revision was limited to a liner exchange for polyethylene wear or osteolysis. Another seven hips underwent revision surgery for recurrent dislocation. Three cups have been revised owing to aseptic loosening. Because of the high incidence of wear-related revisions, Kaplan-Meier survivorship at the 15-year follow-up, using acetabular component revision for any reason as an endpoint, was 75.0% (95% CI 69.4%–83.8%). In contrast, no revision of the femoral stem was performed. Severe stress shielding occurred in 12 hips. Thigh pain was mild, however, and all of the femoral stems remained stable. Conclusions Despite revisions for wear-related complications, the fixation achieved with these porous-coated components remained durable throughout the 15-year follow-up. Acetabular osteolysis has been associated with cup reoperation, but femoral stress shielding has never resulted in stem loosening.

We evaluated triple-phase bone scintigraphy in the differential diagnosis of peri-prosthetic infection in 46 patients with a total hip replacement or bipolar hemiarthroplasty who were due for revision surgery. There were 18 men and 28 women, with a mean age at operation of 64.6 years (28 to 81). We defined peri-prosthetic infection as an increased uptake of radioisotope in all the phases of triple-phase bone scintigraphy and validated these results against the histological and/or microbiology results in every case. The positive and negative predictive values for the presence of infection were 83% and 93%, respectively. The diagnostic sensitivity was 88% and the specificity was 90%. This study indicates that triple-phase bone scintigraphy is a useful tool in the detection of peri-prosthetic infection and offers a cost-effective method of screening.

To develop peptide-based immunotherapy for osteosarcoma, we previously identified papillomavirus binding factor (PBF) as a cytotoxic T lymphocytes (CTL)-defined osteosarcoma antigen in the context of human leukocyte antigen (HLA)-B55. In the present study, we analyzed the distribution profile of PBF in 83 biopsy specimens of osteosarcomas and also the prognostic impact of PBF expression in 78 patients with osteosarcoma who had completed the standard treatment protocols. Next, we determined the antigenic peptides from PBF that react with peripheral T lymphocytes of HLA-A24+ patients with osteosarcoma. Immunohistochemical analysis revealed that 92% of biopsy specimens of osteosarcoma expressed PBF. PBF-positive osteosarcoma conferred significantly poorer prognosis than those with negative expression of PBF (P = 0.025). In accordance with the Bioinformatics and Molecular Analysis Section score, we synthesized 10 peptides from the PBF sequence. Subsequent screening with an HLA class I stabilization assay revealed that peptide PBF A24.2 had the highest affinity to HLA-A24. CD8+ T cells reacting with a PBF A24.2 peptide were detected in eight of nine HLA-A24-positive patients with osteosarcoma at the frequency from 5 × 10−7 to 7 × 10−6 using limiting dilution/mixed lymphocyte peptide culture followed by tetramer-based frequency analysis. PBF A24.2 peptide induced CTL lines from an HLA-A24-positive patient, which specifically killed an osteosarcoma cell line that expresses both PBF and HLA-A24. These findings suggested prognostic significance and immunodominancy of PBF in patients with osteosarcoma. PBF is the candidate target for immunotherapy in patients with osteosarcoma. (Cancer Sci 2008; 99: 368–375)

Background We have previously offered data suggesting a positive linkage of postoperative up-regulation of systemic angiogenic activity and postoperative progression of pulmonary metastasis in osteosarcoma. The finding that the significant down-regulation of endostatin was critical in angio-genic elevation after primary tumor removal suggests that endostatin is a candidate for antiangiogenic therapy for osteosarcoma. Methods In the current study, we evaluated the effect of anti-angiogenic therapy using endostatin on postoperative progression of pulmonary metastasis from osteosarcoma. Mouse osteosarcoma cell line LM 8 cells were inoculated in subcutaneous layer of nude mice. Two weeks after tumor inoculation, the primary tumor was removed surgically, and antiangiogenic therapy using adenovirus encoding endostatin expression vector (Ad5CMV-mEnd) was performed. Two weeks after the antiangiogenic treatment, pulmonary metastasis was evaluated by counting the number of metastatic nodules. The evaluation of systemic angiogenic activity was performed using Matrigel plug assay. Results Two weeks after the viral injection, mice were sacrificed, and the macroscopic pulmonary metastases were counted. Notably, the number of pulmonary metastases was smaller in the mice injected with Ad5CMV-mEnd than in controls, accompanied by significant suppression of systemic angiogenic activity. In addition, the sizes of the pulmonary metastases of the mice injected with Ad5CMV-mEnd were smaller than in the control group. Conclusions Our results indicate that antiangiogenic therapy using endostatin has the potential to prevent postoperative progression of pulmonary metastasis from osteosarcoma. Although this therapeutic strategy cannot provide a cure for osteosarcoma, it should enable osteosarcoma patients to coexist with dormant pulmonary metastasis and lead to improvement of their prognosis.

With the goal of establishing efficacious peptide-based immunotherapy for patients with bone and soft tissue sarcomas, we previously identified the cytotoxic T lymphocyte-defined osteosarcoma antigenic gene Papillomavirus binding factor. The present study was designed to determine the status of HLA class I expression in osteosarcoma and other bone and soft tissue sarcomas. Seventy-four formalin-fixed paraffin-embedded specimens of various bone and soft tissue sarcomas, including 33 osteosarcomas, were stained with the anti-HLA class I monoclonal antibody EMR8-5, which we recently generated. The expression of HLA class I was lost or downregulated in 46 of these specimens (62%). With respect to osteosarcoma, loss or downregulation of HLA class I expression was seen in 13 (52%) of 25 primary tumors and seven (88%) of eight metastatic tumors. In six of 11 HLA class I-negative osteosarcoma specimens, the expression of beta-2 microglobulin was also lost. Subsequently the prognostic significance of HLA class I expression was analyzed in 21 patients with osteosarcoma who had completed multidrug neoadjuvant chemotherapy and undergone adequate surgery. Patients with osteosarcoma highly expressing HLA class I showed significantly better overall and event-free survival than those with HLA class I-negative osteosarcoma. In contrast, such prognostic significance of HLA class I expression was not found in 15 patients with malignant fibrous histiocytoma of soft tissue. These findings suggest that the class I-restricted cytotoxic T lymphocyte pathway plays a major role in immune surveillance of patients with osteosarcoma.

We retrospectively reviewed 11 hip arthroplasties in 7 patients receiving long-term (15 years) hemodialysis for chronic renal failure. Osteonecrosis of the femoral head, osteoarthritis, and amyloid arthropathies were treated by total hip arthroplasty (THA) or bipolar hemiarthroplasty (BHA) using cementless anatomic medullary locking stem. The average follow-up period was 8 years and 3 months (range, 3-13 years). The D'Aubigne and Postel hip score was restored to 14.5 postoperatively from 7.7 preoperatively. All femoral cementless components achieved bone-ingrown fixation. Although 1 BHA resulted in central migration, there was no loosening of the cementless acetabular component. We are encouraged by the predictable long-term stability of the bone-implant interface achieved by cementless fixation with an extensively coated implant. Cementless THA remains a useful treatment option for patients on long-term hemodialysis.

Concomitant tumour resistance (CTR) is a unique phenomenon in which animals harbouring large primary tumours are resistant to the growth of smaller metastatic tumours by systemic angiogenic suppression. To examine this clinically, in ten patients with osteosarcoma, we investigated the effects of removal of the primary tumour on the development of pulmonary metastases, the systemic angiogenesis-inducing ability and the serum levels of several angiogenesis modulators. We found that removal of the primary tumour significantly elevated systemic angiogenesis-inducing ability in five patients who had post-operative recurrence of the tumour. Post-operative elevation of the angiogenesis-induced ability was suppressed by the addition of an angiogenic inhibitor, endostatin. Also, primary removal of the tumour decreased the serum levels of vascular endothelial growth factor and endostatin. These findings suggest, for the first time, the presence of CTR in patients with osteosarcoma for whom postoperative antiangiogenic therapy may be used to prevent the post-operative progression of micrometastases.

A retrospective review was conducted of giant cell tumors treated between 1984 and 1998 using the technique of aggressive curettage through a large bone window followed by acrylic cement reconstruction. Fifteen patients with a mean follow-up time of 46 months (range, 24–188 months) were identified. One patient had a local recurrence 24 months postoperatively. All the patients showed a radiolucent zone at the bone–cement interface up to 2.5 mm in width during the first 6 months after operation. However, the radiolucent zones were nonprogressive and did not affect the stability of the bone cement. Osteoarthritis of the knee joint occurred 14 years postoperatively in one patient with an intraarticular fracture at presentation. A stress fracture occurred in one patient who had the largest tumor in the distal femur. Acrylic cement reconstruction is a safe and effective procedure that provides local adjuvant therapy. Giant cell tumors with an associated intraarticular fracture remain a challenging problem to treat.

To investigate the clinical significance of circulating angiogenic factors, especially in association with early relapse of osteosarcoma, we quantified pre-therapeutic levels of vascular endothelial growth factor, basic fibroblast growth factor and placenta growth factor in the sera of 16 patients with osteosarcoma using an enzyme-linked immunosorbent assay. After a 1-year follow-up, the serum level of angiogenic factors was analysed with respect to microvessel density of the biopsy specimen and clinical disease relapse. The serum vascular endothelial growth factor levels were positively correlated with the microvessel density with statistical significance (P=0.004; Spearman rank correlation) and also significantly higher in seven patients who developed pulmonary metastasis than the remaining nine patients without detectable disease relapse (P=0.0009; The Mann–Whitney U-test). In contrast, the serum levels of basic fibroblast growth factor or placenta growth factor failed to show significant correlation with the microvessel density or relapse of the disease. Although there was no significant correlation between serum vascular endothelial growth factor levels and the tumour volume, the serum vascular endothelial growth factor levels were significantly higher in patients with a vascular endothelial growth factor-positive tumour than those with a vascular endothelial growth factor-negative tumour. These findings suggest that the pre-therapeutic serum vascular endothelial growth factor level reflects the angiogenic property of primary tumour and may have a predictive value on early disease relapse of osteosarcoma. British Journal of Cancer (2002) 86, 864–869. DOI: 10.1038/sj/bjc/6600201 www.bjcancer.com © 2002 Cancer Research UK

CD109, a TGF-β co-receptor, is reported to be preferentially expressed during the early stages of tumorigenesis in several carcinoma types. Myxofibrosarcoma is one of the most common soft-tissue sarcomas found in elderly patients. This study aimed to elucidate the impact of CD109 expression in myxofibrosarcoma on prognosis and recurrence.Immunohistochemical staining for CD109 was performed on archival specimens from 37 patients. The Fisher exact test was used to evaluate association between CD109 expression and other clinicopathological features. Survival analysis was performed using Kaplan-Meier curves, and the prognostic significance was evaluated using the log-rank test. Multivariate analysis of factors was performed using Cox regression analysis.CD109 overexpression was significantly associated with surgical stage and distant metastasis (P = 0.00499, and 0.011, respectively). The frequency of CD109 overexpression was approximately 10% and CD109 overexpression was significantly associated with decreased overall survival (P = 0.004). Five-year overall survival rates 77% and 0% for CD109-negative and CD109-positive patients, respectively. In multivariate analysis, CD109 overexpression was the only independent risk factor for poor outcome (P = 0.02; hazard ratio, 10.64; 95% confidence interval, 1.47-76.91).Immunohistochemical CD109 expression in myxofibrosarcoma was associated with poor prognosis.

The aim of this study was to obtain data on chondral damage and compare the damage patterns of various hip disorders. Data were collected at 100 consecutive arthroscopies, and chondral lesions were recorded on anatomic articular maps divided into different anatomical zones. This geographic zone method made it possible to analyze the ICRS grade and location in relation to the hip morphology. The distribution and degree of the chondral defects showed a hip morphology-specific pattern. On the acetabular side, there were high incidences of full-thickness defects in the anterior–superior zone and the middle superior zone in patients with femoroacetabular impingement (FAI) (zone 2: 25.4 % grade 3, 35.5 % grade 4; zone 3: 20.3 % grade 3, 37.2 % grade 4) and borderline dysplasia (zone 2: 31.2 % grade 3, 12.5 % grade 4; zone 3: 18.7 % grade 3, 25 % grade 4). However, in patients with joint laxity, partial-thickness defects were dominant (zone 2: 50 % grade 1, 15 % grade 2; zone 3: 40 % grade 1). In patients with acetabular dysplasia, full-thickness defects extended even to the posterior superior zone (zone 4: 80 % grade 4). On the femoral head side, the incidence of full-thickness cartilage injuries was high in patients with FAI and borderline dysplasia compared to those with joint laxity and acetabular dysplasia. Evaluation of chondral damage using the geographic zone method showed that the pattern of cartilage damage was influenced by hip morphology. Understanding of hip disorder-specific chondral damage patterns may be useful for the development of arthroscopic classification of hip disorders and may lead to the establishment of treatment guidelines. Diagnostic study, Level III.

Background: This study aimed to investigate the expression profile of cyclooxygenase-2 (COX-2) in desmoid tumor specimens and to evaluate the correlation of intratumoral COX-2 expression with pain status. Methods: Sixteen patients with histologically proven desmoid tumors who attended our institution between 2003 and 2010 were enrolled in this study. COX-2 protein expression in desmoid tumors was determined by immunohistochemistry. COX-2 - positive cells had similar morphology to that of mast cells, and therefore, immunohistochemical staining for tryptase was performed in co-localized sections. The number of COX-2 -positive cells in 10 consecutive fields was counted at 400× magnification. Patients were stratified into 2 groups according to the number of COX-2- positive cells, the COX-2 -positive group (≧10 COX-2 -positive cells) and the COX-2 -negative group (

In the present study, we evaluated the safety and effectiveness of SYT‐SSX‐derived peptide vaccines in patients with advanced synovial sarcoma. A 9‐mer peptide spanning the SYT‐SSX fusion region (B peptide) and its HLA‐A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14‐day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freund's adjuvant and then administered subcutaneously six times at 14‐day intervals. In addition, interferon‐α was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six‐injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed‐type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.

Myxofibrosarcoma is characterized by a high local recurrence rate despite optimal surgical treatment. The definition of prognostic factors for recurrence offers high-risk patients a closer follow-up and a multidisciplinary therapeutic approach. A cohort of 23 patients treated for primary myxofibrosarcoma was retrospectively analyzed. The patients (sex and age), tumors (size, stage, tumor location, bone and/or joint attachment), radiological findings (abnormal signal extension in MRI), histological findings (FNCLCC grade and microscopic extension along the muscle fascia), and treatment (surgical margin) characteristics were included in univariate prognostic factor analysis. After a median follow-up of 63.3 months (range 15–191), the overall recurrence rate was 34.7%. Median time between initial surgery and recurrence was 24.8 months (range 8–52). Inadequate surgical margins (p = 0.026) and bone and/or joint attachment (p = 0.001) were associated with an increased recurrence rate. For the further improvement of local recurrence-free survival of patients with myxofibrosarcoma, accurate diagnosis of the tumor extension and adequate planning for the surgical margin should be focused on in cases with bone and/or joint attachment.

Total hip replacement for high dislocation of the hip joint remains technically difficult in terms of preparation of the true acetabulum and restoration of leg length. We describe our experience of cementless total hip replacement combined with a subtrochanteric femoral shortening osteotomy in 20 hips with Crowe grade IV dislocation with a mean follow-up of 8.1 years (4 to 11.5). There was one man and 17 women with a mean age of 55 years (44 to 69) at the time of the operation. After placment of the acetabular component at the site of the natural acetabulum, a cementless porous-coated cylindrical femoral component was implanted following a subtrochanteric femoral shortening osteotomy. The mean Japanese Orthopedic Association hip score improved from a mean of 38 (22 to 62) to a mean of 83 points (55 to 98) at the final follow-up. The mean lengthening of the leg was 14.8 mm (−9 to 34) in patients with iliofemoral osteoarthritis and 35.3 mm (15 to 51) in patients with no arthritic changes. No nerve palsy was observed. Total hip replacement combined with subtrochanteric shortening femoral osteotomy in this situation is beneficial in avoiding nerve injury and still permits valuable improvement in inequality of leg length.

The metal-on-metal bearing total hip prosthesis is expected to reduce the risk of debris-related osteolysis. However, several reports demonstrated that the socket-stem impingement in the metal-on-metal prosthesis due to the implant malposition results in titanium wear debris and secondary metallosis. In this article, we presented a case of massive metallosis due to metal-on-metal impingement. A 60-year woman had severe hip pain due to fracture of the greater trochanter. We planned a revision of the metal-on-metal inlay. Intraoperatively, the trochanteric bursa and joint space were found to be stained black. Black stained granulation tissue was observed between the femoral stem and the great trochanter. Intraoperatively, notching was noticed on both the posteroinferior aspect of the neck of the femoral component and the anterior aspect of the metal liner and polyethylene core. The notch corresponded to the position of impingement between the socket and the femoral neck during the maximum extension of the hip. To clarify the mechanism of cup-neck impingement, the alignment of the prosthesis and pelvic tilt were evaluated. The cup was placed in too much anteverted position. In addition, increased posterior tilt of pelvis in the standing position made the anteversion of the acetabular cup more significant, which enhanced the cup-neck impingement during the gait. Careful attention is necessary for implant alignment and pelvic tilt especially in metal-on-metal-bearing total hip arthroplasty.

Objective Myxofibrosarcoma often shows abnormal signal infiltration along the fascial plane on magnetic resonance imaging (MRI). The objective was to describe this MRI characteristic of myxofibrosarcoma with pathologic findings for comparison. Materials and methods Clinical, histological, and imaging data for 21 patients with myxofibrosarcoma were reviewed retrospectively. Results Seventeen tumors showed a diffuse infiltrative pattern on MRI. All tumors with diffuse infiltrative growth pattern showed borderless extension of atypical cells with moderate nuclear atypia to the muscle fascia. Notably, the remaining four patients with focal growth pattern on MRI also demonstrated infiltrative growth pattern histologically suggesting that myxofibrosarcoma shows an infiltrative growth property even in the lack of infiltrative growth pattern on MRI. Conclusion Most myxofibrosarcoma show an infiltrative growth pattern histologically. Orthopedic oncologist should pay careful attention to accurately assess tumor extension. It seems prudent to resect the entire area of abnormal signal extension seen on MRI whenever possible to obtain an adequate surgical margin of myxofibrosarcoma.

The prognostic implication of SYT-SSX fusion type in synovial sarcomas is still controversial. The aim of this study is to clarify the prognostic impact of fusion type, in association with other clinical factors, in patients with synovial sarcoma in Japan. Data on 108 SYT-SSX fusion transcript-positive patients with synovial sarcoma, treated in 11 tertiary referral cancer centers in Japan, were retrospectively analyzed. The following parameters were examined for their potential prognostic impact: SYT-SSX fusion type, patient age at presentation, sex, primary tumor location, tumor size, histological subtype, histological grade, treatment modalities and disease stage at presentation. Among the patients with localized disease at presentation, 5-year overall survival (OS) for SYT-SSX1 and -2 subgroups were 84.4 and 74.9%, respectively (P=0.244). Five-year metastasis-free survival (MFS) rates were 67.8% for SYT-SSX1 and 68.5% for SYT-SSX2 (P=0.949). Univariate survival analyses for 91 patients with localized disease at presentation showed that tumor size was the only significant prognostic factor for OS (P=0.0033) and MFS (P=0.0029) and the histological grade was marginally significant for MFS (P=0.0785), whereas the SYT-SSX fusion type and other variables were not. Multivariate survival analyses further indicated that tumor size was the most significant independent prognostic factor for OS and MFS and the histological grade was also significant for MFS. In conclusion, the SYT-SSX fusion type is not a significant prognostic factor unlike tumor size, followed by histological grade for patients with localized synovial sarcoma in Japan.

Slipped capital femoral epiphysis is a well-known disorder of the hip in adolescents. In general, the direction of slip of the capital femoral epiphysis on the femoral neck is posterior and inferior, although superior slips have been reported1,2. We report a case of slipped capital femoral epiphysis in which the epiphysis was displaced anteriorly in relation to the neck. The patient and her family were informed that data concerning the case would be submitted for publication. An eleven-year-old girl presented with a two-month history of pain in the right knee. There was no history of trauma to the right hip or knee. Physical examination revealed a well-developed, well-nourished girl. She was 143 cm tall and weighed 39 kg. The body mass index was 19.1. The physical examination was normal, except with regard to the right lower extremity. She walked with a right antalgic gait. The right leg was 2.0 cm shorter than the left. Hip motion was not painful, and there was neither tenderness nor swelling about the right hip. Range of motion of the right hip included 15° of external rotation, 80° of internal rotation, 115° of flexion, and a 30° flexion contracture. As the right hip was flexed, adduction and internal rotation occurred spontaneously. Radiographs and computed tomography revealed an anterior-inferior slip of the capital femoral …

Aims: To study the immunoexpression of cyclo-oxygenase (COX) 2 in osteoblastomas (OBs) and osteosarcomas (OSs), and to assess the utility of immunohistochemical analysis for COX 2 in the differential diagnosis of the two tumour forms. Methods: The immunohistochemical features of COX 2 were studied in 11 OBs and 30 OSs, including 26 high-grade OSs (16 osteoblastic, 7 chondroblastic, and 3 fibroblastic) and 4 low-grade OSs. Results: Tumour cells from all 11 OBs unequivocally showed diffuse, intense and cytoplasmic immunoreactivity for COX 2. Strong cytoplasmic expression of COX 2 was observed in 5 of 26 (19%) high-grade OSs, all chondroblastic. In one osteoblastic-type OS, COX 2 was expressed in the chondroblastic component, but this tumour was considered to be COX 2 negative. No COX 2 expression was noted in atypical osteoblastic cells. Staining in the four low-grade OSs was negative. Conclusion: The results of immunohistochemical analysis of COX 2 suggest that in addition to the routine histopathological evaluation, COX 2 is a valuable diagnostic marker in the distinction between OB and OS.

Despite the availability of effective treatment and well-publicized treatment guidelines for preventing osteoporotic fractures, there are significant gaps in implementing the recommendations, and it is unknown how many patients are treated for prevention of secondary osteoporotic fractures. In this study, we investigate what percentage of osteoporosis patients were treated with antiosteoporotic drugs after osteoporotic fractures of the hip, wrist, and proximal humerus, and we discuss here the need for improvement in the treatment of osteoporosis following fracture.We studied 422 patients with osteoporotic fractures, 91 men and 331 women, with an average age of 77.1 years (range, 52-102 years). The 422 cases consisted of 299 hip fractures, 97 distal radius fractures, and 26 proximal humerus fractures. All patients underwent surgical intervention. The variables were examined to ascertain whether osteoporosis patients were medicated with antiosteoporotic drugs at postfracture.Fifty-five (13%) of the 422 patients received antiosteoporotic medication at postfracture. Pharmaceutical treatment was given in 44 cases (14.7%) of hip fractures, 8 cases (8.2%) of distal radius fractures, and 3 cases (11.5%) of proximal humerus fractures. Thirty-one (7.3% of total) of the 55 patients were taking the same medication pre- and postfracture. Seven (1.7%) of the 55 were administered a different drug compared to before the fracture, and 17 (4%) started to take an antiosteoporotic drug for the first time subsequent to the fracture.The present rate of treatment is insufficient given the high risk of secondary fractures and the availability of appropriate drugs that would reduce that risk.

We performed rotational acetabular osteotomy in order to treat dysplasia of the hip in five ambulatory adults with cerebral palsy. There was one man and four women, with a mean age of 21 years (16 to 27) who were followed up for a mean of 12 years and two months. The mean Sharp angle improved from 52° to 43°, the mean acetabular index from 30.2° to 2.8°, the mean centre-edge angle from −5.6° to 29.2°, and the mean acetabular head index from 49.2 to 88.2. There was no progression of joint degeneration and relief from pain was maintained. Our results suggest that rotational acetabular osteotomy is a valuable option for the treatment of acetabular dysplasia in adults with cerebral palsy who have incapacitating pain in the hip.

Early relapse with distant metastasis often is observed in patients with cancer after resection of the primary tumor. It is considered that resection of the primary tumor induces activation of systemic angiogenesis and enhances progression of remote metastasis. The authors show that resection of the primary osteosarcoma tumor enhances progression of pulmonary metastasis in animal osteosarcoma models. Matrigel plug neovascularization assay revealed that systemic angiogenic activity was elevated after primary tumor removal (tumor intact group, 1.61 +/- 0.21 g/dL; tumor removed group, 4.92 +/- 0.35 g/dL). In addition, serum concentration of the angiogenesis inhibitor, endostatin, decreased significantly after primary tumor removal. Treatment with the antiangiogenic reagent TNP-470 suppressed postoperative progression of pulmonary metastasis. These results indicate the possibility that activation of angiogenic activity after resection of osteosarcoma tumors enhances progression of pulmonary metastasis. The current data also suggest that administration of antiangiogenic reagents can prevent progression of pulmonary metastasis in osteosarcoma postoperatively.

A case of peroneal artery injury subsequently developed into a lesion resembling an extra-articular tenosynovial giant cell tumor, which is a type of pigmented villonodular synovitis (PVNS). This case supports the hypothesis that accident trauma, such as a vascular injury, can be the etiology of PVNS.

We report a case of peri-prosthetic tuberculous infection nine years after total hip arthroplasty in a patient with no history of tuberculosis before the procedure. Further investigation revealed active pulmonary tuberculosis which was thought to have spread haematogeneously to the arthroplasty. The infection did not respond to standard antituberculous drugs. Removal of the prosthesis and insertion of an antibiotic spacer were required.

We report a case with hypersensitivity to CoCr in total hip arthroplasty coupled with conventional polyethylene and CoCr femoral head. The patient complained of left hip pain and systemic fever, and computed tomography imaging revealed a periprosthetic cystic lesion, so we performed revision total hip arthroplasty using a titanium stem and ceramic head and highly crosslinked polyethylene. Hip pain and cystic lesion disappeared 3 years after revision surgery.