Search

En bloc resection is required for treatment of intermediate-grade talar tumors with extraosseous extension (Enneking stage 3) and malignant talar tumors without intra-articular invasion (Enneking stages IA and IIA). After resection, reconstruction options include tibiocalcaneal fusion, frozen autograft, and talar prosthesis; however, a talar prosthesis is preferable because it preserves ankle range of motion, does not cause leg length discrepancy, and is associated with good long-term outcomes. To the best of our knowledge, en bloc resection and reconstruction of a malignant talar tumor has not been previously reported in detail. We report a detailed surgical technique for en bloc resection of a malignant talar bone tumor using combined anterior and lateral approaches followed by reconstruction using a talar prosthesis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Purpose: Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with cancer, such as melanoma, renal cell carcinoma, head and neck cancer, non-small cell lung cancer (NSCLC), and urothelial carcinoma. The extension of life expectancy has led to an increased incidence of bone metastases (BM) among patients with cancer. BM result in skeletal-related events, including severe pain, pathological fractures, and nerve palsy. Surgery is typically required for the treatment of BM in patients with an impending fracture; however, it may be avoided in those who respond to ICIs. We systematically reviewed studies analyzing BM responses to treatment with ICIs., Methods: This study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement and registered in the UMIN Clinical Trials Registry (ID: UMIN000053707). Studies reporting response rates based on the Response Evaluation Criteria in Solid Tumors (RECIST) or the MD Anderson Cancer Center (MDA) criteria specific for BM in patients treated with ICIs were included; reports of fewer than five cases and review articles were excluded. Studies involving humans, published in English and Japanese, were searched. The PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Ultimately, nine studies were analyzed. The Risk of Bias Assessment tool for Non-randomized Studies was used to assess the quality of studies., Results: Based on the MDA criteria, complete response (CR) or partial response (PR) was observed in 44-78% and 62% patients treated with ICIs plus denosumab for NSCLC and melanoma, respectively. According to the RECIST, CR or PR was recorded in 5% and 7-28% of patients treated with ICIs for renal cell carcinoma and urothelial carcinoma, respectively., Conclusion: Although response rates to ICIs for BM are poor, patients treated with ICI plus denosumab for bone metastases with impending fractures from NSCLC and melanoma are likely to avoid surgery to prevent fractures., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Curettage is recommended for the treatment of Campanacci stages 1-2 giant cell tumor of bone (GCTB) in the extremities, pelvis, sacrum, and spine, without preoperative denosumab treatment. In the distal femur, bone chips and plate fixation are utilized to reduce damage to the subchondral bone and prevent pathological fracture, respectively. For local recurrence, re-curettage may be utilized when feasible. En bloc resection is an option for very aggressive Campanacci stage 3 GCTB in the extremities, pelvis, sacrum, and spine, combined with 1-3 doses of preoperative denosumab treatment. Denosumab monotherapy once every 3 months is currently the standard strategy for inoperable patients and those with metastatic GCTB. However, in case of tumor growth, a possible malignant transformation should be considered. Zoledronic acid appears to be as effective as denosumab; nevertheless, it is a more cost-effective option. Therefore, zoledronic acid may be an alternative treatment option, particularly in developing countries. Surgery is the mainstay treatment for malignant GCTB.

Background and Objective: The prognosis of metastatic renal cell carcinoma (RCC) has markedly improved with the advent of molecular targeted therapies and immune checkpoint inhibitors. However, the therapeutic response in patients with bone metastasis remains low; therefore, surgery still plays a significant role in treatment of bone metastasis. It is important to maintain quality of life for patients with bone metastasis from RCC and avoid reoperation after surgery for bone metastasis. Therefore, we investigated the risk factors for reoperation after surgery in patients with bone metastasis from RCC., Methods: We retrospectively studied 103 bones of 97 patients who underwent surgery for bone metastasis of RCC from 2001 to 2023 at our institutions., Results: Reoperation was performed in 10 (9.7%) of 103 bones. There was no correlation between reoperation-free survival and any of the following variables: preoperative and postoperative radiotherapy, site of bone metastasis, indication for surgery (solitary bone metastasis or impending or pathologic fractures), surgical method (intramedullary nailing fixation, curettage, or en bloc resection), preoperative embolization, or survival., Conclusion: The risk of reoperation for bone metastasis of RCC does not appear to be based on the surgical method., (© 2023 Wiley Periodicals LLC.)

Dedifferentiated chondrosarcoma (DDCS) is a high-grade subtype of chondrosarcoma with the bimorphic histological appearance of a conventional chondrosarcoma component with abrupt transition to a high-grade, non-cartilaginous sarcoma. DDCS can be radiographically divided into central and peripheral types. Wide resection is currently the main therapeutic option for localized DDCS. Moreover, the effectiveness of adjuvant chemotherapy remains controversial. Therefore, we performed a systematic review of available evidence to evaluate the effect of adjuvant chemotherapy on localized DDCS. The purpose was to compare the 5-year survival rate among patients treated with surgery plus adjuvant chemotherapy or surgery alone for localized DDCS. The search was conducted in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Of the 217 studies shortlisted, 11 retrospective non-randomized studies (comprising 556 patients with localized DDCS) were selected. The 5-year survival rates were similar between the two treatment groups (28.2% (51/181) vs. 24.0% (90/375), respectively). The overall pooled odds ratio was 1.25 (95% confidence interval: 0.80-1.94; p = 0.324), and heterogeneity I 2 was 2%. However, when limited to peripheral DDCS, adjuvant chemotherapy was associated with prolonged survival ( p = 0.03). Due to the paucity of included studies and the absence of prospective comparative studies, no conclusions can be drawn regarding the effectiveness or ineffectiveness of adjuvant chemotherapy for localized DDCS.

En bloc resection is typically performed to treat giant cell tumors of bone (GCTB), particularly when curettage can be challenging owing to extensive bone cortex destruction with soft tissue extension. Few reports have addressed the clinical outcomes after reoperation for local recurrence in patients with GCTB who underwent en bloc resection. In this multicenter retrospective study, we investigated local recurrence, distant metastasis, malignant transformation, mortality, and limb function in patients treated for local recurrence following en bloc resection for GCTB. Among 205 patients who underwent en bloc resection for GCTB of the extremities between 1980 and 2021, we included 29 with local recurrence. En bloc resection was performed for large tumors with soft tissue extension, pathological fractures with joint invasion, complex fractures, and dispensable bones, such as the proximal fibula and distal ulna. Local re-recurrence, distant metastasis, malignant transformation, and mortality rates were 41.4% (12/29), 34.5% (10/29), 6.9% (2/29), and 6.9% (2/29), respectively. The median Musculoskeletal Tumor Society score was 26 (interquartile range, 23-28). The median follow-up period after surgery for local recurrence was 70.1 months (interquartile range, 40.5-123.8 months). Local recurrence following en bloc resection for GCTB could indicate an aggressive GCTB, necessitating careful follow-up., Competing Interests: The authors declare no conflict of interest.

Background and Objective: The effects of adjuvant chemotherapy on periosteal osteosarcoma are controversial. Therefore, we conducted a systematic review of studies comparing mortality, local recurrence, distant metastasis and secondary malignancy incidence among patients who underwent surgery and (neo-) adjuvant chemotherapy or surgery alone for periosteal osteosarcoma without distant metastases at diagnosis., Methods: Of the 210 studies identified in the search, 13 were included in this study, involving 291 patients with periosteal osteosarcoma in total., Results: The mortality rates in the surgery and (neo-) adjuvant chemotherapy and surgery alone groups were 11.3% (8/71) and 16.3% (16/98), respectively. The overall pooled odds ratio was 0.89 (P = 0.800). The local recurrence rate in the surgery and (neo-) adjuvant chemotherapy group was 12.1% (8/66), while that in the surgery alone group was 17.6% (13/74). The overall pooled odds ratio was 1.31 (P = 0.601). The distant metastasis rate in the surgery and (neo-) adjuvant chemotherapy group was 15.2% (10/66) and that in the surgery alone group was 10.8% (8/74). The overall pooled odds ratio was 1.51 (P = 0.444). The incidence of secondary malignancy in the surgery and (neo-) adjuvant chemotherapy group was 7.6% (9/118) and that in the surgery alone group was 2.7% (2/74). The overall pooled odds ratio was 2.29 (P = 0.187)., Conclusions: Adjuvant chemotherapy did not appear to improve the prognosis of patients with periosteal osteosarcoma. No association was found between the use of adjuvant chemotherapy and development of secondary malignancies., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Following curettage of giant cell tumor of bone (GCTB), it is common to fill the cavity with polymethylmethacrylate (PMMA) bone cement, bone allograft, or artificial bone to maintain bone strength; however, there is a 2-14% risk of postoperative fractures. We conducted this retrospective study to clarify the risk factors for fractures after curettage for GCTB of the extremities., Methods: This study included 284 patients with GCTBs of the extremities who underwent curettage at our institutions between 1980 and 2018 after excluding patients whose cavities were not filled with anything or who had additional plate fixation. The tumor cavity was filled with PMMA bone cement alone (n = 124), PMMA bone cement and bone allograft (n = 81), bone allograft alone (n = 63), or hydroxyapatite graft alone (n = 16)., Results: Fractures after curettage occurred in 10 (3.5%) patients, and the median time from the curettage to fracture was 3.5 months (interquartile range [IQR], 1.8-8.3 months). The median postoperative follow-up period was 86.5 months (IQR, 50.3-118.8 months). On univariate analysis, patients who had GCTB of the proximal or distal femur (1-year fracture-free survival, 92.5%; 95% confidence interval [CI]: 85.8-96.2) presented a higher risk for postoperative fracture than those who had GCTB at another site (100%; p = 0.0005). Patients with a pathological fracture at presentation (1-year fracture-free survival, 88.2%; 95% CI: 63.2-97.0) presented a higher risk for postoperative fracture than those without a pathological fracture at presentation (97.8%; 95% CI: 95.1-99.0; p = 0.048). Patients who received bone grafting (1-year fracture-free survival, 99.4%; 95% CI: 95.7-99.9) had a lower risk of postoperative fracture than those who did not receive bone grafting (94.4%; 95% CI: 88.7-97.3; p = 0.003)., Conclusions: For GCTBs of the femur, especially those with pathological fracture at presentation, bone grafting after curettage is recommended to reduce the risk of postoperative fracture. Additional plate fixation should be considered when curettage and cement filling without bone grafting are performed in patients with GCTB of the femur. This should be specially performed for those patients with a pathological fracture at presentation., (© 2022. The Author(s).)

Metastatic bone disease is a common complication of malignant tumours. As cancer treatment improves the overall survival of patients, the number of patients with bone metastases is expected to increase. The treatments for bone metastases include surgery, radiotherapy, and bone-modifying agents, with patients with a short expected prognosis requiring less invasive treatment. Patients with metastatic bone disease show greatly varying primary tumour histology, metastases sites and numbers, and comorbidities. Therefore, randomised clinical trials are indispensable to compare treatments for these patients. This editorial reviews recent findings on the diagnosis and prognosis prediction and discusses the current treatment of patients with metastatic bone disease., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

We performed a systematic analysis of existing studies to determine whether preoperative denosumab reduces the risk of local recurrence for patients with giant cell tumor of bone treated with en bloc resection and to address the optimal duration of preoperative denosumab with respect to the risk of local recurrence after en bloc resection. Denosumab did not decrease the risk of local recurrence after en bloc resection; the proportion of patients with local recurrence was 3.6% (2 of 56) in the en bloc resection with preoperative denosumab group vs 14.2% (40 of 280) in the en bloc resection alone group, with an overall pooled odds ratio of 0.76 ( P =.67). Meta-regression models revealed no association between the duration of preoperative denosumab and the odds of local recurrence after en bloc resection ( P =.83). Administration of denosumab for 3 months before en bloc resection is appropriate for sufficient bone hardening to reduce tumor cell spillage and does not result in denosumab-related complications. [ Orthopedics . 2021;44(6):326-332.].

The number of patients with bone metastasis increases as medical management and surgery improve the overall survival of patients with cancer. Bone metastasis can cause skeletal complications, including bone pain, pathological fractures, spinal cord or nerve root compression, and hypercalcemia. Before initiation of treatment for bone metastasis, it is important to exclude primary bone malignancy, which would require a completely different therapeutic approach. It is essential to select surgical methods considering the patient's prognosis, quality of life, postoperative function, and risk of postoperative complications. Therefore, bone metastasis treatment requires a multidisciplinary team approach, including radiologists, oncologists, and orthopedic surgeons. Recently, many novel palliative treatment options have emerged for bone metastases, such as stereotactic body radiation therapy, radiopharmaceuticals, vertebroplasty, minimally invasive spine stabilization with percutaneous pedicle screws, acetabuloplasty, embolization, thermal ablation techniques, electrochemotherapy, and high-intensity focused ultrasound. These techniques are beneficial for patients who may not benefit from surgery or radiotherapy.

Background: Denosumab, a monoclonal antibody that binds to receptor activation of nuclear factor-kappa ß ligand (RANKL), has been used as a drug to treat aggressive giant cell tumors of bone. It is unclear whether preoperative denosumab therapy is associated with the local recurrence risk in patients with giant cell tumors of bone treated with curettage. Early evidence suggests that denosumab treatment is associated with a reduction in local recurrence, but other studies have questioned that premise. Curettage after a short course of denosumab (3 to 4 months) has been recommended, especially for large, aggressive giant cell tumors in which complete curettage is difficult to achieve. No randomized studies have documented the benefit of this approach, and some investigators have reported higher local recurrence after denosumab treatment. Due to this confusion, we performed a systematic analysis of existing reports to attempt to answer this question and determine whether the appropriate preoperative denosumab therapy duration could be established., Questions/purposes: (1) Is the use of preoperative denosumab associated with local recurrence risk in patients with giant cell tumors of bone treated with curettage compared with those treated with curettage alone? (2) Is the preoperative denosumab therapy duration associated with local recurrence after curettage?, Methods: We searched the PubMed, EMBASE, and CENTRAL databases on April 26, 2019 and included both randomized and non-randomized studies that compared local recurrence between patients who had giant cell tumors of bone and were treated with curettage after preoperative denosumab and patients treated with curettage alone. Two authors independently screened the studies. There were no randomized studies dealing with denosumab in giant cell tumors of bone, and generally, denosumab was used for more aggressive tumors. We assessed the quality of the included studies using the Risk of Bias Assessment tool for Non-randomized Studies, with a moderate overall risk of bias. We registered our protocol in PROSPERO (registration number CRD42019133288). We selected seven eligible studies involving 619 patients for the final analysis., Results: The proportion of patients with local recurrence ranged from 20% to 100% in the curettage with preoperative denosumab group and ranged from 0% to 50% in the curettage-alone group. The odds ratio of local recurrence ranged from 1.07 to 37.80 in no more than 6 months of preoperative denosumab duration group and ranged from 0.60 to 28.33 in more than 6 months of preoperative denosumab duration group., Conclusions: The available evidence for the benefit of denosumab in more aggressive giant cell tumors is inconclusive, and denosumab treatment may even be associated with an increase in the proportion of patients experiencing local recurrence. Because there are no randomized studies and the existing studies are of poor quality due to indication bias (the most aggressive Campanacci 3 lesions or those where even a resection would be difficult and result in morbidity are generally the patients who are treated with denosumab), the evidence to suggest a disadvantage is weak. Denosumab treatment should be viewed with caution until more definitive, randomized studies documenting a benefit (or not) have been conducted. Furthermore, we could not find evidence to suggest an appropriate length of preoperative denosumab before curettage.

Background: There are conflicting reports for the outcome of the patients with giant cell tumor of bone (GCTB) and pathological fracture at presentation treated with curettage or resection. This study compared local recurrence, complications, and function after curettage versus resection for these patients., Materials and Methods: We retrospectively studied the files of 46 patients with histologically confirmed GCTB of the extremities admitted and treated from 1982 to 2015. The median follow-up was 79.5 months (57.0-125.5 months). We evaluated local recurrence and type of surgery-related complications with imaging and function with the Musculoskeletal Tumor Society (MSTS) score., Results: Overall local recurrence was 6.5%. There were one patient with curettage and two patients with resection; local recurrence rate was similar between the two procedures but the time to local recurrence was shorter after curettage. MSTS score was significantly better after curettage. Complications occurred in two patients after curettage and in five patients after resection; because of the low number of patients with complications, a statistical comparison was not possible; however, by direct comparison of the numbers, complications were more common after resection compared with curettage., Conclusion: Curettage is recommended for GCTB and pathological fracture at presentation because of similar local recurrence but better function compared with resection. The treating physicians should be aware and inform their patients for a shorter time to local recurrence after curettage and for more complications after resection., (© 2019 Wiley Periodicals, Inc.)

Few studies have examined the relationship between functional outcome and sociooccupational or psychological status in adolescent and young adults (AYA) generation and childhood sarcoma patients. We retrospectively analyzed clinical (prognostic and functional) and sociooccupational outcomes in 50 patients; 22 children aged under 14 years and 28 AYAs generation (15 to 29 y). There were 35 cases of bone sarcomas and 15 of soft tissue sarcomas. Limb-sparing surgery was performed in 30 of 37 extremity cases. The most prevalent problems among patients were as follows: limited activities; drop-out or delayed studies among high school and college students; limitation in job searching; and changes in social relationships. These problems were unaffected by limb-sparing. Regression analysis between functional and sociooccupational disability showed that the correlation coefficient was significant (P=0.005) in all limb-salvaged patients, but there was no significant correlation among osteosarcoma patients (P=0.07). These findings suggest that quality of life is a multidimensional measure: it depends on physical status, spiritual health, and social well-being of both patients and family members. To overcome the disadvantages of this type of disease, it is essential to provide comprehensive care at the earliest convenience using multidimensional approaches.

Purpose: There are conflicting reports on the effect of denosumab on lung metastases in patients with giant cell tumor (GCT) of bone. To address these reports, we performed this study to determine if denosumab prevents lung metastasis and to evaluate univariate and multivariate predictors for lung metastases in these patients., Materials and Methods: We retrospectively studied 381 GCT patients with surgery alone and 30 GCT patients with surgery and denosumab administration. The median follow-up was 85.2 months (IQR, 54.2-124.4 months). We evaluated lung metastases and local recurrences, univariate and multivariate predictors for lung metastases, response, and adverse events of denosumab administration., Results: The occurrence of lung metastases was similar (surgery alone 4.7%, 18 patients; denosumab administration 3.3%, 1 patient); however, the occurrence of local recurrences was significantly higher in the patients with denosumab administration. Denosumab administration was not an important predictor for lung metastases; Campanacci stage and type of surgery were the only univariate predictors for lung metastases, and type of surgery and local recurrence were the only multivariate predictors for lung metastases. Histology showed viable tumour in all tumor specimens of the patients with denosumab administration., Conclusion: Denosumab does not decrease the risk of lung metastases in patients with bone GCT; the only important predictors for lung metastases in these patients are type of surgery and local recurrence. However, because the number of patients with lung metastases was small for a multivariate analysis, the possibility of denosumab's effect could not be completely eliminated.

Purpose: The treatment of giant cell tumor (GCT) of bone remains controversial. Intralesional surgery (curettage) results in a higher rate of local recurrence, but better functional results compared to resection. The aim of this study was to assess whether the use of curettage was successful in the treatment of GCT of long bones. We evaluated the influence of adjuvant treatment, local tumor presentation, and demographic factors on the risk of recurrence., Methods: We retrospectively reviewed the records of patients treated for GCT of long bones between 1990 and 2013, using curettage. No patient had any treatment other than surgery. After detailed curettage, the bone cavity was filled with bone allografts and/or cement. Recurrence rates, risk factors for recurrence and the development of pulmonary metastases were determined. The minimum follow-up was 24 months., Results: We enrolled 210 patients with GCT of long bones treated by curettage. The rate of local recurrence was 16.2% (34/210 patients). The median follow-up was 89.2 months. In the multivariate analysis, no significant statistical effect on the local recurrence rate could be identified for gender, patient's age, Campanacci's grading, or cement versus bone allografts. The only independent risk factor related to the local recurrence was the site, with a statistically significant higher risk for patients with GCT of the proximal femur., Conclusions: Our observation on the correlation of tumor location and risk of local recurrence is new. We suggest that patients with GCT of bone in the proximal femur should be followed closely soon after surgery to identify any possible recurrence.

Introduction: The purpose of our study is to verify possible clinical and radiological findings with regard to distinguishing enchondroma from atypical cartilaginous tumour (ACT). In addition, this study determined risk factors that are associated with local recurrence of enchondroma or ACT treated with curettage., Materials and Methods: We retrospectively reviewed the records of 54 patients with enchondroma and 35 patients with ACT of the long bones treated by curettage between 1986 and 2015. The minimum follow-up was 18 months. The relationship between clinical and radiological factors and the tumour type or local recurrence was assessed using Chi-square test or Fischer exact test., Results: Endosteal scalloping (p = 0.004) and soft tissue extension (p = 0.017) were shown to statistically favour ACT over enchondroma; by contrast, pain (p = 0.034) was more frequent in enchondroma compared to ACT. All patients with enchondroma had no local recurrence; in contrast, local recurrence occurred in four patients with ACT (11%). Soft tissue extension (p = 0.049) and the diagnosis of ACT (p = 0.021) were associated with an increased risk of local recurrence. We had a disease progression in three of four patients with local recurrence, and these had higher histological grade than the original tumour., Discussion: Our data show that endosteal scalloping and soft tissue extension could be helpful in the differential diagnosis between enchondroma and ACT. We suggest following only those patients with ACT after surgery to identify any possible recurrence and, in case of recurrence, treat these patients with resection for the risk of disease progression.

Ubiquilin 2 (UBQLN2), a member of the ubiquitin-like protein family (ubiquilins), maintains protein homeostasis. Although UBQLN2 has been implicated in the pathogenesis of neurodegenerative diseases, it is also associated with malignant tumors. Therefore, we examined whether UBQLN2 plays a role in human osteosarcoma. The human osteosarcoma cell line MG63 was transfected with UBQLN2 siRNA and cultured under hypoxic conditions. The rat osteosarcoma cell line COS1NR was inoculated into Fischer 344 rats, followed by injection of UBQLN2 siRNA with atelocollagen. An immunohistochemical analysis of UBQLN2 was performed using 34 cases of human high-grade osteosarcomas, and metastasis-free survival was estimated by the Kaplan-Meier method. Silencing of UBQLN2 by siRNA transfection under hypoxia led to activation of JNK and p38, resulting in induction of apoptosis in the osteosarcoma cell line MG63. Injection of UBQLN2 siRNA suppressed tumor growth in the rat osteosarcoma model, followed by apoptosis induction. The immunohistochemical examination revealed that high UBQLN2 expression was significantly associated with the unfavorable metastasis-free survival of osteosarcoma patients. UBQLN2 plays an important role in resistance to hypoxic stress and enhances tumor progression in osteosarcoma. UBQLN2 may be a new molecular target for chemotherapeutics and a useful clinicopathological marker in human osteosarcoma.

We report a case of primary Ewing sarcoma of the proximal phalanx of the right middle finger in an 18-year-old boy. He was treated with neoadjuvant chemotherapy, followed by ray amputation. To restore maximum function, the index ray was transferred to the base of the third metacarpal bone and fixed with a plate. The function of his right hand after the operation was excellent and the cosmetic appearance acceptable. There was no evidence of local recurrence or metastasis after 20 months follow up.

Spindle cell hemangioma is a rare benign tumor characterized by cavernous blood vessels and spindle cell proliferation. It typically arises in the subcutis of the distal extremities, particularly in the hand. Spindle cell hemangioma of periosteal origin is extremely rare, and our extensive literature search did not find any reports of this condition. We report here a case of spindle cell hemangioma of periosteal origin arising from the right fibula of a 49-year-old woman. Pathological examination of a needle biopsy specimen indicated the possibility of low-grade spindle cell sarcoma, and the patient underwent resection of the fibular diaphysis with a wide margin. Subsequent examination of the surgical specimen revealed a diagnosis of periosteal spindle cell hemangioma. Follow-up examination at 10 months showed no evidence of local recurrence or metastasis. A large tissue sample was required for definitive diagnosis in this case. Spindle cell hemangioma behaves in a benign fashion, but recurrence occurs in about 60% of cases. Excision of the fibula was a reasonable course of management in this case because these patients usually maintain good function. Reports of additional cases will be required to determine the most appropriate treatment for this tumor.

We present a case of high-grade osteosarcoma in the proximal humerus in an 8-year-old boy. Massive tumor expansion required a S12345B shoulder girdle resection according to the system of the Musculoskeletal Tumor Society. After wide resection, only a small portion of the distal humerus and none of the rotator cuff muscles would be spared. Because the humeral portion would be too short to support the stem and the soft tissue would be insufficient to cover prosthetic components, we designed a composite reconstruction using a frozen autograft and a pedicled muscle flap. At 2 years postoperatively, our patient exhibited good adaptation and had acquired fine dexterity of the upper limb. To our knowledge, this is the first report regarding a successful composite reconstruction after a S12345B shoulder girdle resection., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Although mesenchymal stem cells (MSCs) are considered to be the cells of origin for most sarcomas, the role of MSCs as a source of tumor stroma is not fully understood in this tumor type. The current study investigated whether MSCs affect the tumor growth and metastatic ability in rat osteosarcoma model. Results from subcutaneous co-implantation of rat osteosarcoma COS1NR cells, established in our laboratory, with rat MSCs isolated from femur bone marrow showed that the incidence of tumor formation and tumor growth rate was higher until 5 weeks compared to COS1NR cell inoculation alone. However, no difference was observed in tumor growth afterwards and in the number of metastatic nodules at 9 weeks (0.75 vs. 1.2). Intravenous MSC injection at weeks 3 and 5 after subcutaneous inoculation of COS1NR cells significantly increased the number of lung nodules in the group with MSC injection compared to the group without MSC injection (17.33 vs. 2.0), while no difference was observed in subcutaneous tumor growth between those groups. Pathway analysis from gene expression profile identified that genes involved in focal adhesion, cytokine-cytokine receptor and extracellular matrix-receptor pathways such as CAMs (ICAM and VCAM)-integrins were highly expressed in MSCs, possibly participating in the tumor progression of osteosarcoma. These results suggest that MSCs could provide a source of microenvironments for osteosarcoma cells, and might enhance the ability of settlement and colonization which lead to early onset of growth and metastasis, possibly through their activated pathways interaction.

Bisphosphonates (BPs) are agents used for treating disorders of excessive bone resorption. In addition, due to their cell-killing activity, BPs were potent candidates for adjuvant cancer therapy. On the other hand, low-concentrations of BPs have been reported to increase cellular viability in several types of tumor cells. Therefore, we focused on the effect of BPs on cellular aggressiveness of malignant bone tumors at low concentrations. MTS assay was performed using osteosarcoma cell lines MG63 and HOS, fibrosarcoma cell line HT1080, and prostate cancer cell line PC3. All the cell lines showed toxicity at high concentrations. On the other hand, at lower concentrations, the cellular viabilities of HOS and MG63 were rather higher than those of untreated controls. Since this tendency was most evident, HOS was used for further assays, including cellular motility, bone resorption activity, and cathepsin K activity. The low-concentration of alendronate enhanced cellular viability and motility, which correlated with the expression of connexin 43 at the mRNA and protein levels. Interestingly, oleamide, a potent connexin 43 inhibitor, had an inhibitory effect on the enhanced proliferation. Our data suggest that alendronate may enhance the proliferation of osteoblastic cell line through connexin 43 activation., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Background: Abdominosacral amputation is a potentially curative surgical approach for patients with recurrent rectal cancer. Previous reports have described differing extents of sacral resection. Most of these reports stated that high sacral involvement of the tumor is a contraindication for surgery; however, the basis for this is unclear., Methods: In this study, we reviewed the highest level of sacral amputation and the "contraindications" for this technique. Using a systematic literature survey, we analyzed the theoretical basis and the changes in surgical indications for recurrent rectal cancer., Results: We retrieved 33 articles from Medline and one study from the Cochrane Center Register of Controlled Trials. The highest level of resection was at the level of L5/S and S1 in one article, S1/2 and S2 in nine articles and S2/3 and S3 in 11 articles. Fifteen articles stated contraindications regarding sacral level, including tumor involvement of S1, the S1/2 junction, or the level above the S2/3 junction. Reasons stated for these contraindications included the risks associated with surgery, namely bladder dysfunction, anorectal dysfunction, genital dysfunction, walking disorder, and spinal fluid leak. In terms of the rationale for the contraindications, three articles referred to four previously published reviews or case series. None of these supporting publications were randomized controlled trials and they did not include any statistical evaluation., Conclusion: The consensus for contraindications for sacral amputation was formed empirically, without strong supporting evidence. The balance between curability and dysfunction should be further evaluated scientifically.

Elevated aldehyde dehydrogenase 1 (ALDH1) has been proposed as one of the possible candidates for a stem cell maker that can be used for the isolation of cancer stem cells from cancers such as leukemia and breast cancer. In the current study, we found that subpopulations with elevated ALDH1 were present in the human sarcoma cell lines, MG63 (osteosarcoma) and HT1080 (fibrosarcoma), using Aldefluor assay. Both ALDH1 positive and negative cell populations were isolated from the MG63 cell line, by cell-sorting using FACSAria. Both subpopulations had a comparable ability to differentiate similarly to the parental MG63, under normal monolayer culture condition. Subpopulations with the ability to form spheres in anchorage-independent, serum-starved conditions showed increased ALDH1 mRNA expression in addition to strong mRNA expression of the stem cell-related genes, such as Nanog, Oct3/4, Stat3 and Sox2, and possessed ability for self-renewal with secondary sphere formation. Sarcosphere cells from the MG63 cell line showed strong chemo-resistance against both doxorubicin and cisplatin compared with monolayer, adherent cells. In conclusion, sphere-forming cells with elevated ALDH1 are a possible candidate for sarcoma stem cells, possessing strong chemo-resistant capacities. Although ALDH1 elevation was not sufficient for representing sarcoma stem cells, the efficient detoxification could contribute to the chemo-resistant properties of the stem-like sphere cells form human sarcoma.

Unlabelled: BACKGROUND DATA AND OBJECTIVES: We present here a case report of a patient with metaphyseal osteosarcoma with a preserved epiphysis and reconstructed by a vascularized fibular graft and hydroxyapatite composites., Methods: The case was a 14-year-old boy, who had osteosarcoma in the proximal tibia. After the diagnosis was confirmed by biopsy, the patient immediately received preoperative chemotherapy including high-dose Methotrexate, Cisplatin and Doxrubicin. Imagings after preoperative chemotherapy including MRI and contrasted enhanced CT confirmed no tumor penetration into the physis. Subsequently, we performed transepiphyseal resection of the proximal tibia to reserve the joint surface. The intercalary twin-barreled vascularized fibular graft was placed with hydroxyapatite composites. The patella tendon was reattached to the grafted fibular to biologically reconstruct the knee extensor mechanism. Postoperative chemotherapy was completed with the same regime as preoperative chemotherapy., Outcomes: The bony union was completed at 10 months after the operation. The Enneking's functional evaluation score was 28 out of 30 points (93%). There was no evidence of local recurrence and no metastatic disease during the 42 months follow-up after initial diagnosis., Conclusion: An accurate evaluation of MRI and CT can give a reliable assessment of intraphyseal penetration of metaphyseal osteosarcoma. In case of no involvement of the tumor in the physis, transepiphyseal osteotomy is the optimal procedure to preserve the joint surface and superior function of the joint, especially in the proximal tibia.

Background: Despite findings from individual studies regarding prognostic factors for Ewing sarcoma, no conclusive results have been produced, partly because of small sample sizes. The objective of the current study was to evaluate whether the presence of p16(INK4a) alteration is associated with a poorer prognosis in patients with Ewing sarcomas., Methods: A review was conducted of publications that assessed associations between p16(INK4a) status and 2-year survival among patients with Ewing sarcoma. The association between metastatic disease at initial diagnosis and 2-year survival was evaluated by synthesizing data in the form of risk ratios., Results: Of 11 studies that were identified in the initial search strategy, 6 studies, representing 188 patients, met the inclusion criteria and, consequently, were pooled for quantitative analyses. The estimated pooled risk ratio of p16(INK4a) aberration was 2.17 (95% confidence interval [95% CI], 1.55-3.03; P < .001), whereas the estimated pooled risk ratio of metastasis at diagnosis among the 164 eligible patients was 2.60 (95% CI, 1.71-3.97; P < .001). There was no statistically significant difference in the pooled estimated risk ratios of p16(INK4a) aberration for a poor prognosis between patients with and without metastasis at diagnosis (1.86 and 2.21, respectively; P > .59)., Conclusions: The presence of p16(INK4a) alteration was a statistically significant predictor of prognosis for patients with Ewing sarcoma. Along with other prognostic factors, such as metastasis, the p16(INK4a) alteration may be a potential candidate for improving the risk-stratifying strategy for patients with these tumors., ((c) 2007 American Cancer Society.)

Recent studies have advocated the genotypic and phenotypic delineation of a novel Ewing's sarcoma histologic variant showing epithelial features defined as "adamantinoma-like Ewing's sarcoma". We described an 18-year-old girl with a primary small round-cell sarcoma of the right tibia showing polyphenotypic differentiation with epithelioid features. The neoplastic cells had mainly round or oval nuclei with fine chromatin with a portion of epithelial arrangements. The immunohistochemical analysis showed the epithelial markers of cytokeratin 5/6/18, AE1/AE3, and cytokeratin high molecular weight were stained especially in the foci with epithelioid features, as well as MIC2, S100, and NSE. The diagnosis of the lesion was confirmed as Ewing's sarcoma by the presence of the EWS-FLI1 fusion transcript, and could be defined as the so-called "adamantinoma-like Ewing's sarcoma". After wide excision and high-dose chemotherapy with peripheral blood stem cell transfusion, the patient has been well and continuously event-free for 3 years since the initial diagnosis.

Seven samples from seven patients with juxtacortical osteosarcomas, and 27 samples from 19 patients with conventional high-grade osteosarcomas were investigated for a possible correlation between telomerase activity and clinicopathological features such as age, sex, and response to chemotherapy. Of seven juxtacortical osteosarcomas, telomerase activity was weakly positive in three parosteal osteosarcomas, and highly positive in one parosteal osteosarcoma. In contrast, of 27 conventional high-grade osteosarcomas, telomerase activity was weakly positive in eight tumors and highly positive in three. Of all samples, 44.1% of the osteosarcomas showed telomerase activity (57.1% of juxtacortical and 40.7% of conventional osteosarcomas). The majority of poor responders to chemotherapy showed no telomerase activity (nine of 11), whereas five of seven good responders showed strong or weak telomerase activity. There was a significant correlation between telomerase activity and the response to chemotherapy (P<0.05). Telomerase activity was not correlated with MIB-1 proliferation index, age at the time of surgery, or sex. These findings suggest that telomerase activation occurs early in the oncogenesis of osteoblastic tumors without having an effect on the progression of these tumors. In malignant osteoblastic tumors, the biological significance of telomerase activation is different from that described for most epithelial cancers.

STI571 is a 2-phenylaminopyrimide derivative that was designed as an Abl tyrosine kinase inhibitor, but it is also effective against platelet-derived growth factor receptor (PDGFR) and c-Kit tyrosine kinase. Recent studies have demonstrated that STI571 inhibits the growth of several tumors in which PDGF or c-kit play an important role in tumor pathogenesis. We have recently established rat osteosarcoma and malignant fibrous histiocytoma (MFH) cell lines. RT-PCR analysis revealed that MFH and osteosarcoma cell lines expressed high and very low levels of PDGFR alpha respectively, and that all cell lines expressed similar levels of PDGFR beta. The level of c-kit mRNA expression were almost negligible hardly in all cell lines. The effect of STI571 on cellular growth measured by MTS colorimetric dye reduction showed that the growth of each cell line was inhibited in a dose- and time-dependent manner. STI571 (10 microM) inhibited the rates of cell growth of MFH cells by up to 40% and of osteosaroma cells by only to 20% after 72 hours. These data suggested that STI571 tyrosine kinase inhibitor plays a role in blocking or slowing the rate of growth of MFH and osteosarcoma cells expressing tyrosine kinase type receptor.

Aminopeptidase N (APN/CD13), a Zn2+-dependent ectopeptidase, is localized on the cell surface and functions as a transmembrane protein. Increased expression and activity of APN have been postulated to correlate with the aggressive behavior of several tumor types. In this study, the osteosarcoma cell line MNNG/HOS was stably transfected with an expression vector capable of expressing the antisense transcript of APN. Four stably transfected clones, the control clones and parental cells were characterized. Stable integration of the antisense vector was confirmed by PCR analysis of genomic DNA. Competitive RT-PCR revealed that mRNA expression of antisense-transfectants was decreased to approximately 37% of the control cell line. The activity assay showed that the enzymatic activity of APN was inhibited to approximately 51% of the control cell line. Antisense-transfection had no influence on the cellular proliferation measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, on the motility in Transwell chambers, and on the adhesive potential to collagen I. However, an in vitro invasion assay revealed a significant decrease in the number of cells that migrated through a reconstituted membrane (51% of the control cell line). The adhesive potential to Matrigel was also affected (73% of the control cell line). Furthermore, under in vivo conditions, a reduced potency to metastasize to the lung was shown in an experimental metastasis assay in nude mice. These findings demonstrate that APN plays an active role in the cellular attachment and proteolytic degradation of the extracellular matrix in the metastatic process of osteosarcomas.