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Case: We reconstructed the knee extension mechanism using a novel procedure for a 16-year-old adolescent girl with osteosarcoma that invaded her femur, patella, and patellar tendon. The knee joint was replaced with a megaprosthesis, and the extension mechanism was reconstructed using artificial ligaments sandwiched with bone cement forming a patella. At the one-year follow-up, she could walk using a knee orthosis without crutches., Conclusions: Reconstruction of the knee extension mechanism after patellectomy remains challenging. Our new method achieved an acceptable knee function and is, therefore, useful for patients undergoing excision of the knee joint and extension mechanism., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C45)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Curative treatment of inoperable post-irradiation sarcoma is often challenging, especially using radiotherapy, wherein curative dose administration is difficult because the organs around the tumor have already been irradiated during the first cancer treatment. Carbon-ion radiotherapy (C-ion RT) might be useful in the treatment of post-irradiation sarcomas because it allows re-irradiation with high-dose localization properties and also demonstrates higher cytotoxic effects on radioresistant tumors compared with X-rays. This study presents the long-term survival of two patients with inoperable post-irradiation pelvic osteosarcoma treated with C-ion RT after uterine cervical cancer treatment., Case Presentation: The durations from prior radiotherapy to the diagnosis of post-irradiation osteosarcoma were 112.8 and 172.2 months, respectively. Both patients received 70.4 Gy (relative biological effectiveness) in 16 fractions of C-ion RT, and chemotherapy was performed before and after C-ion RT. Both patients achieved a complete response 1 year after the initiation of C-ion RT. However, one patient developed single lung metastasis 12.6 months after the initiation of C-ion RT and underwent thoracoscopic lobectomy. After 63.7 and 89.0 months from the initiation of C-ion RT, respectively, the patients were alive with no evidence of local recurrence, other distant metastasis, or fatal toxicities., Conclusions: The study findings suggest that C-ion RT is a suitable treatment option for inoperable post-irradiation osteosarcoma., (© 2022. The Author(s).)

Purpose: This prospective phase I trial was conducted to evaluate the safety of percutaneous cryoablation for osteoid osteoma (OO)., Materials and Methods: Nine patients with OO (mean tumor size: 5.9 mm; tibia, n = 5; femur, n = 2; lumbar spine, n = 2) were enrolled and treated with percutaneous cryoablation. The primary endpoint was the evaluation of the treatment safety as determined using step-by-step registration. The secondary endpoints were the incidence and grade of adverse events by CTCAE version 4.0, and the short-term efficacy of this treatment. Based on a decrease in the numerical rating scale (NRS) score, efficacy was classified as significantly effective (SE ≥ 5 or reached 0-2), moderately effective (ME 2-4), or not effective (NE < 2 or increase)., Results: Cryoablation procedures were completed in all patients. Major adverse events (≥ grade 3) related to the procedure were not observed. Minor adverse events (≤ grade2) were observed in 22-67%. The mean NRS score was 7 before treatment, 0.6 at 4-week, 0.1 at 6-month, and 0 at 1-year post-treatment. All procedures were classified as SE., Conclusion: Percutaneous cryoablation is a safe treatment for OO. Future phase II trials with large patient cohorts are warranted.

The skeleton is frequently a secondary growth site of disseminated cancers, often leading to painful and devastating clinical outcomes. Metastatic cancer distorts bone marrow homeostasis through tumor-derived factors, which shapes different bone tumor microenvironments depending on the tumor cells' origin. Here, we propose a novel insight on tumor-secreted Galectin-3 (Gal-3) that controls the induction of an inflammatory cascade, differentiation of osteoblasts, osteoclasts, and bone marrow cells, resulting in bone destruction and therapeutic failure. In the approaching era of personalized medicine, the current treatment modalities targeting bone metastatic environments are provided to the patient with limited consideration of the cancer cells' origin. Our new outlook suggests delivering individual tumor microenvironment treatments based on the expression level/activity/functionality of tumor-derived factors, rather than utilizing a commonly shared therapeutic umbrella. The notion of "Gal-3-associated bone remodeling" could be the first step toward a specific personalized therapy for each cancer type generating a different bone niche in patients afflicted with non-curable bone metastasis.

Management of bone metastasis remains clinically challenging and requires the identification of new molecular target(s) that can be therapeutically exploited to improve patient outcome. Galectin-3 (Gal-3) has been implicated as a secreted factor that alters the bone microenvironment. Proteolytic cleavage of Gal-3 may also contribute to malignant cellular behaviors, but has not been addressed in cancer metastasis. Here, we report that Gal-3 modulates the osteolytic bone tumor microenvironment in the presence of RANKL. Gal-3 was localized on the osteoclast cell surface, and its suppression by RNAi or a specific antagonist markedly inhibited osteoclast differentiation markers, including tartrate-resistant acid phosphatase, and reduced the number of mature osteoclasts. Structurally, the 158-175 amino acid sequence in the carbohydrate recognition domain (CRD) of Gal-3 was responsible for augmented osteoclastogenesis. During osteoclast maturation, Gal-3 interacted and colocalized with myosin-2A along the surface of cell-cell fusion. Pathologically, bone metastatic cancers expressed and released an intact form of Gal-3, mainly detected in breast cancer bone metastases, as well as a cleaved form, more abundant in prostate cancer bone metastases. Secreted intact Gal-3 interacted with myosin-2A, leading to osteoclastogenesis, whereas a shift to cleaved Gal-3 attenuated the enhancement in osteoclast differentiation. Thus, our studies demonstrate that Gal-3 shapes the bone tumor microenvironment through distinct roles contingent on its cleavage status, and highlight Gal-3 targeting through the CRD as a potential therapeutic strategy for mitigating osteolytic bone remodeling in the metastatic niche., (©2016 American Association for Cancer Research.)

Background: The results of treatment for malignant bone and soft-tissue tumors arising from the deep trunk and pelvis are still not acceptable due to the relatively high recurrence and low overall survival rates. Recently, carbon ion radiotherapy (CIRT) was applied for several malignancies, including bone and soft-tissue sarcomas, and provided favorable results. However, it has been unclear what modalities should be used for evaluating the response and for the follow-up of these patients. Here, we analyzed the methods used to predict local recurrence and to find local failures or metastases., Methods: We analyzed 37 patients with bone and soft-tissue tumors who received CIRT at our institute. The patients were examined with FDG positron emission tomography (PET) and enhanced MRI before and three months after CIRT. The pre-treatment maximum standardized uptake value (SUVmax), and that three months after treatment, the difference between the pre- and post-CIRT SUVmax, the ratio of the post- to pre-SUVmax in FDG-PET and the size of the tumors were evaluated as predictors for local recurrence. FDG-PET and enhanced MRI were used to detect local recurrence., Results: Local recurrence appeared in 10 cases after CIRT. Nine of the 10 lesions (90.0 %) were detected with FDG-PET, while enhanced MRI detected just 50.0 % of the recurrences. One case of local recurrence, in which the lesion was negative on FDG-PET, was detected using enhanced MRI. A receiver operating characteristic curve analysis showed that neither the SUVmax on FDG-PET nor the tumor size before or three months after CIRT could be used to predict local recurrence., Conclusions: The combination of FDG-PET and enhanced MRI is recommended to detect local recurrence for patients with sarcomas who have received CIRT; however, no parameters obtained during the examinations performed before and three months after CIRT accurately predicted the development of local recurrence.

L-type amino acid transporter-1 (LAT1) is expressed in many cancers. We examined LAT1 and CD98 expression immunohistochemically in surgically resected specimens of various bone and soft tissue tumors. Out of 226 cases, 79 (35%) were LAT1(+) and 95 (42%) were CD98(+) . In bone tumors, LAT1 was highly expressed in osteoblastoma (89%), chondrosarcoma (50%), and osteosarcoma (60%); in soft tissue tumors, LAT1 was highly expressed in rhabdomyosarcoma (80%), synovial sarcoma (63%), Ewing's sarcoma (60%), epithelioid sarcoma (100%) and angiosarcoma (100%). In malignant soft tissue tumors, LAT1 expression was associated with higher histological grade. High CD98 expression was seen in many bone tumors of intermediate and high malignancy. Among soft tissue tumors, CD98 was expressed in tendon sheath giant cell tumor and malignant peripheral nerve sheath tumor (57%), Ewing's sarcoma (50%) and undifferentiated sarcoma (64%). Some of the malignant soft tissue tumors expressed both LAT1 and CD98. This study showed that LAT1 and CD98 was expressed in many malignant and intermediate bone tumors, and some malignant soft tissue tumors., (© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

Metastasis to the lymph nodes is relatively rare in malignant bone and soft-tissue tumors, and its risk factors remains unknown, except for tumors of the lymphogenous histotype, including rhabdomyosarcoma, epithelioid sarcoma, and clear cell sarcoma. The purpose of this study was to identify the risk factors for lymph node metastasis of malignant bone and soft-tissue tumors. We retrospectively reviewed 242 patients with malignant bone and soft-tissue tumors. The predictors of interest for the risk of lymph node metastasis included age, sex, histopathological diagnosis, location(s) of the primary tumor(s), local recurrence, residual tumor(s), and the size of the primary tumors. To identify the risk factors for lymph node metastasis, Cox regression analyses were performed. Among the 242 patients with malignant bone and soft-tissue tumors in the current study, 60, 29, and 28 were detected to have lung, lymph node, and bone metastases, respectively. In the univariate analyses, the lymphogenous histotype and a primary tumor invading the subcutis were the risk factors for lymph node metastasis. In the multivariate analysis, the lymphogenous histotype (P < 0.01) and a primary tumor in the subcutis (P < 0.01) remained significantly associated with a higher risk of lymph node metastasis with 5.15 and 3.48 of hazard ratios, respectively. Lymph node metastasis was detected in malignant bone and soft-tissue tumors more frequently than that has been previously reported, and the risk factors for lymph node metastasis were the lymphogenous histotype and primary tumors invading the subcutis.

Osteochondroma of the carpal is rare. We found only 1 case of osteochondroma of the trapezium in the literature. We present a case of a 52-year-old woman with an osteochondroma of the left trapezium and trapeziometacarpal arthritis., (Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Combined chemotherapy including 5-FU plus radiation treatment resulted in a synergistic effect has been reported. S-1 enhances a radiation response of colon cancer cell line xenografts. Also the effectiveness of S-1 + radiation therapy has been reported. A 66-year-old man underwent a low anterior resection for lower rectal cancer. Adjuvant chemotherapy was not performed due to Stage II rectal cancer. Twenty months after the operation, solitary sacral bone metastasis was found during the postoperative work-up. S-1 (120 mg/day) combined with radiotherapy was performed on days 1-14 and 21-35. Radiation (3 Gy) was administered a total of 45 Gy on days 1-5, 7-12 and 35-40. Moreover, the reduction was judged as complete response after 11 courses of mFOLFOX 6. There has been no sign of recurrence for 44 months. It suggested that local control therapy (S-1 + radiation) plus systemic chemotherapy (mFOLFOX6) was one of the promising effective therapies for single sacral bone metastasis of rectal cancer.

Individualization of high-dose methotrexate (MTX) dosing is important to achieve therapeutic levels (700-1,000 microM) for osteosarcoma. Therefore we developed a pharmacokinetically (PK) individualized dosage regimen to maintain MTX concentrations of 700 microM (1 h bolus followed by 5 h maintenance infusion) and evaluated its safety and efficacy. Loading and maintenance doses were calculated by the PK parameters based on 2-compartment model analysis. Thirty-two courses of chemotherapy were performed in 9 patients with osteosarcoma. The maximum concentrations during maintenance infusion in 31 courses (97%) were above 700 microM. Only 1 patient developed severe hepatotoxicity as adverse effect. Total body clearance of MTX decreased in 4 patients when weekly MTX chemotherapy was performed for 3 consecutive weeks. Although the clearance was changed, the average MTX concentrations were maintained at about 700 microM by the PK individualization. The 5-year survival rate was 77.8% (7 of 9 patients), and all of them have survived for more than 9 years. This PK individualization is safe and useful for tailoring high-dose MTX therapy to achieve therapeutic levels.

We retrospectively reviewed 71 histopathologically-confirmed bone and soft-tissue metastases of unknown origin at presentation. In order to identify the site of the primary tumour all 71 cases were examined with conventional procedures, including CT, serum tumour markers, a plain radiograph, ultrasound examination and endoscopic examinations, and 24 of the 71 cases underwent 2-deoxy-2-[F-18] fluoro-D-glucose positron emission tomography (FDG-PET). This detected multiple bone metastases in nine patients and the primary site in 12 of the 24 cases; conventional studies revealed 16 primary tumours. There was no significant difference in sensitivity between FDG-PET and conventional studies. The mean maximal standardised uptake value of the metastatic tumours was significantly higher than that of the primary tumours, which is likely to explain why FDG-PET did not provide better results. It was not superior to conventional procedures in the search for the primary site of bone and soft-tissue metastases; however, it seemed to be useful in the staging of malignancy.

To gain the insight into the involvement of signaling mediated by the mammalian target of rapamycin (mTOR) in the phenotype and biological profiles of tumors and tumor-like lesions of the bone and soft tissue, we analyzed the expression and phosphorylation (activation) of mTOR and its correlation with the status of upstream and downstream modulator proteins Akt, p70S6-kinase (S6K), and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), which we refer to collectively as mTOR cassette proteins. Immunohistochemical analysis of 140 cases showed activation of Akt in 55% (61% in malignant and 27% in benign), and mTOR expression in 61% (66% in malignant and 39% in benign). The preponderance of mTOR activation was found in tumors of peripheral nerve sheath (malignant peripheral nerve sheath tumor and schwannoma), skeletal muscle origin (rhabdomyosarcoma), and in those exhibiting epithelial nature (chordoma and synovial sarcoma). Together with the result of immunoblotting analysis, it was shown that many of those particular tumors with mTOR activation exhibited activation of Akt, S6K, and 4E-BP1, suggesting the constitutive activation of the Akt/mTOR pathway. In addition, although activation of the Akt/mTOR pathway was largely independent of activation of epidermal growth factor receptor (EGFR), mutation of EGFR was frequently accompanied by constitutive activation of Akt-mTOR-S6K/4E-BP1. By clinicopathological analysis, activation of Akt correlates with statistically higher probability of metastasis. We conclude that mTOR-mediated signaling proteins function not only in the proliferation of the tumor cells, but also in the differentiation and/or maintenance of morphological phenotypes in tumors of rhabdomyoblastic and nerve sheath cell origin. Furthermore, mTOR signaling may also modulate morphogenesis of tumors exhibiting epithelial nature. Additionally, activated Akt may have a function in metastasis. Overall, these results suggest that inhibitors of mTOR cassette may be useful as novel components of combined chemotherapy for a defined subset of bone and soft tissue sarcomas.

Background and Purpose: The defect that results after curettage of a bone tumor is usually filled in the same way. We report the outcome in patients with benign bone tumors that were treated with curettage but no filling., Patients and Methods: We retrospectively studied 78 patients (mean age at the time of operation was 27 (6-73) years, 44 men) who had had a benign bone tumor curetted with no filling of the defect. The commonest tumor types were giant cell tumor of bone (27), fibrous dysplasia (13), enchondroma (9), and simple bone cyst (7). The mean size of the lesions was 35 (2-196) cm(3). Normal activities, including full weight bearing for lower extremity lesions, were allowed after 3 months or less. The patients were followed for an average of 10 (1.2-21) years., Results: A postoperative fracture with a minor displacement occurred in 3 patients, in 2 of them because of local recurrence. All fractures healed. Local recurrence occurred in 9 patients; 7 of them had a giant cell tumor. Repeated local recurrences necessitated above-knee amputation in 1 patient. All other patients had unrestricted activities of daily living., Interpretation: Routine filling of curetted bone lesions does not appear to be necessary from a mechanical point of view.

Response to neoadjuvant chemotherapy is a significant prognostic factor for osteosarcoma (OS). 18-F-fluorodeoxy-D: -glucose (FDG) positron emission tomography (PET) is a noninvasive imaging modality that correlates with histological grading in musculoskeletal sarcomas. To determine the prognostic value of FDG PET in patients receiving chemotherapy, 13 patients were evaluated by FDG-PET, and followed for more than 4 years. FDG PET standardized uptake values before (SUV1) and after (SUV2) chemotherapy were analyzed and correlated with the expression of metastasis-related glycolytic enzyme, autocrine motility factor (AMF)/phosphoglucose isomerase (PGI) by immunohistochemical examination in surgically excised tumors. Although mean SUV1 for OS patients with metastatic lesions were similar to those in the completely disease-free (CDF) group (6.5 vs. 6.6, respectively, P = 0.975), mean SUV2 for OS with metastatic lesions were significantly higher than those in the CDF group (5.1 vs. 2.5, respectively, P = 0.0445). Interestingly, immunohistochemical analysis using anti-AMF/PGI antibody revealed that SUV2 correlated significantly with the AMF/PGI staining titers (P = 0.0303), while no correlation between SUV1 and the AMF/PGI staining titers existed (P = 0.964). The present study suggests that FDG PET after chemotherapy may provide information for AMF/PGI-related metastatic potentiality of residual tumors located out side of the area surgically resected afterward, and then lead to a useful prediction of the patients' prognosis.

In order to assess the involvement of autocrine motility factor (AMF) in mesenchymal tumours, AMF protein and mRNA expression was analysed in tumours, tumour-like lesions, and other lesions of bone and soft tissue. Immunohistochemical analysis of 200 cases revealed positive staining in 72.5% of the cases, suggesting that AMF is a widely expressed protein. Chordoid, chondroid, and muscular tumours revealed higher immunoreactivity in both benign and malignant tumours. Immunoblotting analysis corroborated the results of immunohistochemistry. Generally, malignant tumours revealed higher expression of AMF than benign tumours of the same histopathological lineage, except for dermatofibroma/dermatofibrosarcoma protuberans. However, mRNA levels were not concordant with protein levels, and sarcomas that displayed higher mRNA and lower protein expression levels showed a trend for distant metastasis. In cultured cells, AMF was secreted and detected in conditioned culture medium. Furthermore, when proteasome inhibitors were added to cells in order to examine the changes in turnover rates, these compounds did not significantly alter the intracellular levels of AMF protein. On the basis of these overall findings, it is suggested that a particular subset of sarcomas secrete AMF, rather than degrading this protein at a higher turnover rate. This secreted AMF presumably enhances their cell motility through an autocrine effect and eventually causes increased metastatic potential. Collectively, AMF was observed in a wide spectrum of lesions of mesenchymal tissue, supporting the notion that it is involved in various cellular functions, including proliferation, differentiation, metabolism, and metastasis. In addition, higher expression of its mRNA may indicate higher levels of protein secretion and define a particularly aggressive group of tumours with high metastatic potential., (Copyright 2005 Pathological Society of Great Britain and Ireland.)

The shoulder girdle presents unique features for the preoperative planning of musculoskeletal tumors. This is the first trial to evaluate positron emission tomography (PET) analysis for preoperative planning in shoulder girdle tumors. Fifty-two patients were examined with fluorine 18 fluoro-2-deoxy-D-glucose (FDG)-PET and/or alpha-methyltyrosine (FMT)-PET. Imaging findings were visually inspected in conjunction with computed tomography and/or magnetic resonance imaging, and standardized uptake values (SUVs) were generated. FDG-PET may be useful for the detection of malignant tumors and screening for metastatic spread, with the qualitative assessment of heterogeneous biologic activity providing a correct approach for biopsy. The mean SUVs for malignant tumors were significantly higher than those for benign lesions. However, a useful cutoff SUV was not found in either FDG- or FMT-PET for differentiating malignant from benign tumors from receiver operating characteristic curve analysis. SUVs on FDG- and FMT-PET may merely be limited to differentiating malignant from benign tumors in the shoulder girdle.

Purpose: Recently, a new positron emission tomography (PET) tracer, carbon-11 choline, has been introduced in oncology investigations, but the role of choline PET in musculoskeletal tumor evaluation has not been previously examined. This is the first trial to investigate the utility of choline PET in evaluating musculoskeletal tumors in comparison with fluorine-18 fluoro-2-deoxy-D-glucose (FDG) PET., Method: Thirty-three patients were examined with both choline PET and FDG PET, of which standardized uptake values (SUVs) were used for evaluation of the lesions. To decide the appropriate cutoff value and compare the two PET studies, receiver operating characteristic curve analysis was used. The binomial test was used for comparison of sensitivities between choline PET and FDG PET., Results: A significant correlation (r = 0.537, P = 0.0013) between choline and FDG SUVs was noted for all lesions (n = 33). Mean SUVs for malignant tumors were significantly higher than those for benign lesions in both choline PET and FDG PET. Using a cutoff value of 2.7 for choline SUVs, the sensitivity for correctly diagnosing malignancy was 92.3% (12/13) with a specificity of 90.0% (18/20), resulting in an accuracy rate of 90.9%. With use of a cutoff value of 3.3 for SUVs in FDG PET, the sensitivity was 84.6% (11/13) with a specificity of 80.0% (16/20), resulting in an accuracy rate of 81.8%. The receiver operating characteristic curves of two analyses showed that the mean area under the curve value of choline PET (0.9577 +/- 0.041) was significantly greater (P = 0.0488) than that of FDG PET (0.8192 +/- 0.0806). There was no significant difference in sensitivity and specificity between choline PET and FDG PET analysis using either the binomial test (P = 0.4531) or McNemar test (P = 0.371)., Conclusion: Choline PET analysis may not be inferior to FDG PET analysis for differentiating malignant from benign musculoskeletal tumors. The advantages of choline PET were shorter examination time and little retention in the bladder; therefore, this modality may be useful for preoperative planning for musculoskeletal tumors, especially for lesions around the hip joints.

Positron-emission tomography (PET) can provide an in vivo method for evaluating metabolism and physiology in normal and diseased tissues. Clinical trials with [(18)F]2-deoxy-2-fluoro- d-glucose (FDG), the most commonly used radiolabeled tracer for PET imaging, have demonstrated increased accumulation of FDG in several cancer tissues. In this article, we introduce the basic principles of FDG-PET and review current knowledge about FDG-PET for evaluating musculoskeletal tumors. Recent reports and our own experience suggest that FDG-PET cannot be a screening method for differential diagnosis between benign and malignant musculoskeletal lesions, including many neoplasms originating from different tissues altogether. FDG-PET might not accurately reflect the malignant potential of musculoskeletal tumors, but rather might implicate cellular components included in the lesions. A high accumulation of FDG can be observed in histiocytic, fibroblastic, and some neurogenic lesions, regardless of whether they are benign or malignant. More specific uses of FDG-PET, such as grading, staging, and monitoring of musculoskeletal sarcomas, should be considered for each tumor of a different histologic subtype.

Reconstruction of the knee joint for osteosarcoma of the proximal tibia is a formidable challenge. Here we present two patients whose knees were reconstructed with autologous grafts of whole-knee joint treated by extracorporeal pasteurization. Incorporation at the junction between host and pasteurized bone was evident. On the other hand, direct reattachment of the patellar tendon to the pasteurized tibia was not successful in case 1. In case 2, in contrast, the patella was divided followed by successful reconstruction at the osseous site. Avoiding reattachment of pasteurized ligamentous structure is recommended. The operation protocol is not ideal but so far may be superior to other reconstruction procedures because there are many fundamental complications such as low long-term survival of a massive prosthesis and the lethal risk of transfection (e.g. human immunodeficiency virus); moreover, immunological responses of the allograft can be avoided.

We describe 27 cases of bone tumours or tumour-like lesions where there was spontaneous regression. The follow-up period was 2.8-16.7 years (average, 7.0 years). Fourteen of these cases were no longer visible on plain radiographs. Histological diagnosis included exostosis, eosinophilic granuloma, fibrous dysplasia, fibrous cortical defect, non-ossifying fibroma, osteoid osteoma and bone island. Most cases began to reduce in adolescence or earlier, although sclerotic type lesions showed their regression in older patients. All lesions thought to be eosinophilic granuloma began to regress after periods of less than 3 months, while the duration of the other lesions showed wide variation (1-74 months). As resolution of the lesions took between 2 and 79 months (mean, 25.0 +/- 20.3 months) we consider that the most likely mechanism was recovery of normal skeletal growth control. In exostosis with fracture, alteration of vascular supply may contribute to growth arrest, but not to subsequent remodelling stage. In inflammatory-related lesions such as eosinophilic granuloma, cessation of inflammation may be the mechanism of growth arrest, whilst temporary inflammation may stimulate osteogenic cells engaged in remodeling. In the sclerotic type, growth arrest is a less probable mechanism. Necrosis within the tumour and/or local changes in hormonal control, plus remodelling of the sclerotic area takes longer. Knowledge of the potential for spontaneous resolution may help in management of these tumour and tumour-like lesions of bone., (Copyright 2001 The Royal College of Radiologists.)

Protein-independent cells are useful for analysis of proteins that are produced by the cells themselves without any consideration of exogenous proteins. This experimental protein-independent tumor system provides new biology of the autonomous nature of neoplastic cells during their evolution. We established a Dunn protein-free osteosarcoma (DPF) cell line, which was derived from parental fetal calf serum (FCS)-dependent murine Dunn osteosarcoma (DOS) cells. The DPF cells grew in a chemically defined protein-free medium at the high seeding density of 1x10(4) cells/well of a 96-well-plate with a similar doubling time to that of cells growing in the presence of FCS, while the cells did not grow at a density lower than 1x10(3)/well. Furthermore, addition of conditioned medium stimulated the growth in a dose-dependent manner. In contrast, DOS did not grow in the protein-free condition at all. Morphological examination revealed that DPF cells exhibited a more round shape than DOS cells. RT-PCR analysis exhibited the augmentation of the RNA message of bone morphogenetic protein-4 (BMP-4) and osteocalcin in DPF cells. Enhanced expression of BMP-4 protein was also demonstrated by immunoblot analysis. Furthermore, alkaline phosphatase (ALP) activity was higher in DPF cells, indicating that bone-formation related molecules may be overexpressed in protein-independent osteosarcoma cells. These results suggest that putative growth factors may play a role in the DPF cell growth in an autocrine fashion, and the acquisition of autonomous growth independent of exogenous proteins may be coupled to the osteogenic differentiation.

Fluorine-18 labelled alpha-methyltyrosine (FMT) was developed for positron emission tomography (PET) imaging, and its potential for clinical application in patients with brain tumours has been demonstrated. This is the first trial to compare FMT with 18F-fluoro-2-deoxy-D-glucose (FDG) for the evaluation of musculoskeletal tumours. Seventy-five patients were examined with both FMT- and FDG-PET within a 2-week period. Imaging findings were visually inspected in conjunction with computed tomography and/or magnetic resonance imaging, and standardized uptake values (SUVs) for both FMT and FDG in lesions were also generated and compared with histological findings. A significant correlation between FMT and FDG SUVs was found for all lesions (r=0.769, P<0.0001), and mean values for malignant tumours were significantly higher than those for benign lesions in both FMT- and FDG-PET. The diagnostic sensitivities and specificities for malignancy were 72.7% and 84.9%, respectively, using FMT with a cut-off SUV of 1.2, and 72.7% and 66.0%, respectively, using FDG with a cut-off SUV of 1.9. The resultant accuracy with FMT was 81.3%, higher than that for FDG (68.0%), and the difference with respect to specificity was significant (chi2cal=5.0625, P<0.05). On the other hand, while a significant correlation was found between malignant tumour grade and SUV with both FMT- (rho=0.656) and FDG-PET (rho=0.815), only the latter demonstrated significant differences among grades I, II and III. FMT and FDG for PET appear equally effective at detecting musculoskeletal tumours. In evaluating musculoskeletal tumours, FMT may be superior to FDG in the differentiation between benign and malignant tumours, while FDG may be the better choice for non-invasive malignancy grading.

We performed positron emission tomography (PET) with 18 fluorine-fluoro-2-deoxy-D-glucose (FDG) on 55 patients with tumours involving the musculoskeletal system in order to evaluate its role in operative planning. The standardised uptake value (SUV) of FDG was calculated and, to distinguish malignancies from benign lesions, the cases were divided into high (> or =1.9) and low (< 1.9) SUV groups. The sensitivity of PET for correctly diagnosing malignancy was 100% with a specificity of 76.9% and an overall accuracy of 83.0%. The mean SUV for metastatic lesions was twice that for primary sarcomas (p < 0.0015). Our results suggest that the SUV may be useful in differentiating malignant tumours from benign lesions. However, some of the latter, such as schwannomas, had high SUVs so that biopsy or wide resection was selected as the first operation. Thus, some other quantitative analysis may be required for preoperative planning in cases of high-SUV neurogenic benign tumours. The reverse transcription-polymerase chain reaction revealed that the RNA message of a key enzyme in glucose metabolism, phosphohexose isomerase (PHI)/autocrine motility factor, was augmented in only high FDG-uptake lesions, suggesting that a high expression of the PHI message may be associated with accumulation of FDG in musculoskeletal tumours.

Osteosarcoma was detected in two siblings. Their human leukocyte antigen (HLA) phenotypes were completely identical, although they were different from those of osteosarcoma patients in previous reports. Despite an extensive search of family and past history, no significant background related to the induction of cancer could be found. These cases suggest that genetic similarity may influence the development of osteosarcoma. Ascertainment of the HLA phenotypes in siblings with osteosarcoma might be a useful strategy to facilitate the early diagnosis of this tumor.