PURPOSE: To examine the expression of Connective Tissue Growth Factor (CTGF) in osteosarcoma and to evaluate its role in osteosarcoma invasion and proliferation. MATERIALS AND METHODS: The mRNA expression of CTGF from 23 patient-derived osteosarcoma cell lines was examined, and the role of CTGF in cell invasion and proliferation was examined using siRNA transfection. RESULTS: The over-expression of CTGF mRNA was observed in 17 cell lines (74%). CTGF-specific siRNA transfection into SaOS-2 and MG63 cell lines resulted in efficient knockdown of CTGF expression on Western blot analysis. siRNA transfected cells showed decreased migration on Matrigel invasion assay and decreased cell proliferation on WST-1 assay. CONCLUSION: These results indicated that the CTGF expression may play an important role in osteosarcoma progression, and may be a therapeutic target of osteosarcoma.
Blotting, Western ; Cell Line ; Cell Proliferation ; Connective Tissue Growth Factor ; Osteosarcoma* ; RNA, Messenger ; RNA, Small Interfering ; Transfection

BACKGROUND: The pelvic bone is the most common site of bone metastases following the axial skeleton. Surgery on the pelvic bone is a demanding procedure. Few studies have been published on the surgical outcomes of metastasis to the pelvic bone with only small numbers of patients involved. This study sought to analyze the complications, local progression and survival after surgery for metastasis to the pelvic bone on a larger cohort of patients. METHODS: We analyzed 83 patients who underwent surgery for metastases to the pelvic bone between the years 2000 and 2015. There were 41 men and 42 women with a mean age of 55 years. Possible factors that might be associated with complications, local progression and survival were investigated with regard to patient demographics and disease-related and treatment-related variables. RESULTS: The overall complication rate was 16% (13/83). Advanced age (> 55 years, p = 0.034) and low preoperative serum albumin levels (≤ 39 g/L, p = 0.001) were associated with increased complication rates. In patients with periacetabular disease, the complication rate was higher in those who underwent total hip replacement arthroplasty (THR) than those who did not (p = 0.030). Local progression rate was 46% (37/83). The overall median time to local progression was 26 ± 14.3 months. The median time from local progression to death was 13 months (range, 0 to 81 months). The local progression-free survival was 52.6% ± 6.4% at 2 years and 36.4%± 7.6% at 5 years, respectively. Presence of skip lesions (p = 0.017) and presence of visceral metastasis (p = 0.027) were found to be significantly associated with local progression. The median survival of all patients was 24 months. The 2-year and 3-year survival rates were 52.5% ± 5.9% and 35.6% ± 6%, respectively. Metastasis from the kidney, breast, or thyroid or of hematolymphoid origin (p = 0.014), absence of visceral metastasis (p = 0.017) and higher preoperative serum albumin levels (p = 0.009) were associated with a prolonged survival. CONCLUSIONS: Advanced age and low serum albumin levels were associated with high complication rates. Local progression after surgery for metastases to the pelvic bone was affected by the presence of skip lesions, not by surgical margins. Primary cancer type, serum albumin level and visceral metastasis influenced survival.
Arthroplasty ; Arthroplasty, Replacement, Hip ; Bone Neoplasms ; Breast ; Cohort Studies ; Demography ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Kidney ; Male ; Neoplasm Metastasis* ; Pelvic Bones* ; Serum Albumin ; Skeleton ; Survival Rate ; Thyroid Gland

BACKGROUND: Comorbidity has not been examined as an independent prognostic factor in soft tissue sarcoma (STS). We examined the prognostic impact of comorbidity on oncologic outcome in STS with an adjustment for possible confounding factors. METHODS: A retrospective review was performed on 349 patients who had undergone surgery for high-grade localized STS of extremity at our institute. Conditions known to alter the risk of mortality, as defined in the Charlson comorbidity index, were classified as comorbidities and 43 patients (12%) had at least one comorbidity at the time of surgery. The association of comorbidity and oncologic outcomes of local recurrence-free survival (LRFS) and disease-specific survival (DSS) were tested with adjustment for confounding factors. RESULTS: Comorbidity was associated with old age, high tumor grade, and large tumor size. The presence of comorbidity was independently associated with poor LRFS and DSS, even after adjusting for confounding factors including age and treatment variables. CONCLUSIONS: Our data suggest that the presence of comorbidity is an independent prognostic factor for extremity STS.
Adult ; Age Factors ; Comorbidity ; Confounding Factors (Epidemiology) ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Sarcoma/*epidemiology/surgery ; Survival Analysis

BACKGROUND: Injectable calcium sulfate is a clinically proven osteoconductive biomaterial, and it is an injectable, resorbable and semi-structural bone graft material. The purpose of this study was to validate the clinical outcomes of injectable calcium sulfate (ICS) grafts as compared with those of a demineralized bone matrix (DBM)-based graft for filling in contained bony defects created by tumor surgery. METHODS: Fifty-six patients (41 males and 15 females) with various bone tumors and who were surgically treated between September 2003 and October 2007 were included for this study. The patients were randomly allocated into two groups, and either an ICS graft (28 patients) or a DBM-based graft (28 patients) was implanted into each contained defect that was developed by the surgery. The radiographic outcomes were compared between the two groups and various clinical factors were included for the statistical analysis. RESULTS: When one case with early postoperative pathologic fracture in the DBM group was excluded, the overall success rates of the ICS and DBM grafting were 85.7% (24/28) and 88.9% (24/27) (p > 0.05), respectively. The average time to complete healing was 17.3 weeks in the ICS group and 14.9 weeks in the DBM group (p > 0.05). Additionally, the ICS was completely resorbed within 3 months, except for one case. CONCLUSIONS: Although the rate of resorption of ICS is a concern, the injectable calcium sulfate appears to be a comparable bone graft substitute for a DBM-based graft, with a lower cost, for the treatment of the bone defects created during surgery for various bone tumors.
Absorbable Implants ; Adolescent ; Adult ; Biocompatible Materials/*administration & dosage ; Bone Demineralization Technique ; Bone Matrix/*transplantation ; Bone Neoplasms/radiography/surgery/*therapy ; Bone Substitutes/*administration & dosage ; Calcium Sulfate/*administration & dosage ; Child ; Child, Preschool ; Curettage ; Female ; Humans ; Infant ; Injections ; Male ; Middle Aged ; Wound Healing ; Young Adult

BACKGROUND: We report on our experience with using a distally based island flap for soft tissue reconstruction of the foot in limb salvage surgery for malignant melanoma patients. METHODS: A distally based sural flap was used for 10 cases for the hindfoot reconstruction, and a lateral supramalleolar flap was used for 3 cases for the lateral arch reconstruction of the mid- and forefoot after wide excision of malignant melanomas. RESULTS: The length of the flap varied from 7.5 cm to 12 cm (mean, 9.6 cm) and the width varied from 6.5 cm to 12 cm (mean, 8.8 cm). Superficial necrosis developed in four flaps, but this was successfully treated by debridement and suture or a skin graft. All thirteen flaps survived completely and they provided good contour, stable and durable coverage for normal weight bearing. CONCLUSIONS: The distally based sural flap is considered to be useful for reconstructing the hindfoot, and the lateral supramalleolar flap is good for reconstructing the lateral archs of the mid- and forefoot after resection of malignant melanoma of the foot.
Adult ; Aged ; Female ; Foot/*surgery ; Foot Diseases/*surgery ; *Free Tissue Flaps ; Humans ; Limb Salvage ; Male ; Melanoma/*surgery ; Middle Aged ; Reconstructive Surgical Procedures/methods ; Skin Neoplasms/*surgery

Non-spine bone metastasis accounts for approximately 20% of all skeletal metastases, but little data have been published that focused on bone metastasis to the pelvis and extremities as an initial manifestation of cancer. We determined 1) clinicopathologic characteristics of patients who presented with non-spine bone metastasis of unknown primary malignancy, and 2) process by which the diagnosis of primary cancer was made. We retrospectively reviewed 84 patients with bone metastasis of unknown primary cancer site at the time of presentation. The study population consisted of 56 men and 28 women, with a mean age of 59.1 yr (17.5-85.6 yr). The average follow-up period was 20.8 months (1-120 mo). Primary cancer site was identified in 79 patients (94.0%), and was determined to be the lung (46.4%), kidney (13.1%), liver (9.5%), thyroid (8.3%), and prostate (4.8%). Five-year overall survival rate was 28.0%. Multiple bone metastases, distant organ metastasis, and multiple bone with organ metastases were the significant prognostic factors in univariate analysis. Multiple bone metastases remained significant after multivariate analysis (P = 0.008). Lung cancer is the most common site of primary cancer, and patients with multiple bone metastases have a poor prognosis, possibly due to disseminated cancer and a greater tumor burden.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms/mortality/pathology/*secondary ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms/pathology ; Liver Neoplasms/pathology ; Lung Neoplasms/pathology/radiography ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms/pathology ; Republic of Korea ; Retrospective Studies ; Survival Rate ; Thyroid Neoplasms/pathology ; Young Adult

Background: Cancer stem cells (CSCs) are cells characterized by their self-renewal and tumorigenic potential. The purpose of this study was to discover the role of the delta-like factor 1 (DLK1) in sarcoma. Methods: mRNA expression of DLK1 from 13 sarcoma cell lines was examined. Isolated CSCs from the tumors were examined using fluorescence-activated cell sorting (FACS) with CD133, the CSC marker, or sphere-forming assay. The relationship between DLK1 and CSCs in sarcoma was examined using cell proliferation and cell invasion assays after they were treated with DLK1 short interfering RNA (siRNA). Results: A high expression of DLK1 mRNA was observed in all sarcoma cell lines. However, CSCs were isolated from over expressed sarcomas of the DLK1 gene, and they have shown to be expressed lower than the wild type. The anti-cancer effects of DLK1 siRNA inhibited cell proliferation and invasion in U2OS, A204, and sw872. In addition, treatment with DLK1 siRNA inhibited cell invasion in sw872 CSCs. DLK1 gene induces tumorigenesis in various sarcoma cells and regulates the invasiveness of liposarcoma. These results suggest that DLK1 could serve as a possible therapeutic target for sarcoma. Conclusions Our study showed that the DLK1 gene induces tumorigenesis in various sarcomas and is associated with invasive mechanism in sarcoma. These results suggest DLK1 could serve as a possible therapeutic target in a variety of sarcomas.

BACKGROUND: We compared indomethacin therapy with the more aggressive approaches of anti-cancer chemotherapy and surgery in the treatment of isolated Langerhans cell histiocytosis (LCH) of bone in children. METHODS: Comparisons were made with respect to healing of the lesion without recurrence, time to radiological healing of the lesion, time to functional recovery, and complications related to treatment. RESULTS: Complete radiologic healing of the lesion (mean, 15.3 months) and functional recovery (mean, 5.6 months) were observed in all patients treated with either approach. No significant differences were noted in the time to complete radiologic healing or the time to functional recovery between the two groups. There were no recurrences with either approach until the last follow-up (mean, 56 months). Complications were common with anti-cancer chemotherapy, but indomethacin was well-tolerated. CONCLUSIONS: Indomethacin seems to be effective for treating isolated LCH of bone in children. Hence, morbidities associated with aggressive treatment approaches such as anti-cancer chemotherapy or surgery can be avoided.
Adolescent ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Bone Diseases/*drug therapy/radiography/radionuclide imaging ; Child ; Child, Preschool ; Cyclooxygenase Inhibitors/*therapeutic use ; Eosinophilic Granuloma/*drug therapy/radiography/radionuclide imaging ; Female ; Humans ; Indomethacin/*therapeutic use ; Infant ; Male ; Recurrence

PURPOSE: The prognostic factors of chondrosarcoma remain uncertain as only a few large studies with long-term follow-up have been reported. The aim of this study was to analyze oncological outcomes and prognostic factors. MATERIALS AND METHODS: A retrospective review of oncological outcomes and prognostic factors was performed on 125 consecutive chondrosarcoma patients who underwent surgery at our institution. RESULTS: Overall survival was 91.6%+/-2.5%, 84.1%+/-3.8%, and 84.1%+/-3.8% at 5, 10, and 15 years respectively. Among the histological types, dedifferentiated type showed the worst survival (p < 0.001). As for conventional type chondrosarcoma, histologic grade and anatomical location predicted outcome, with high-grade with axial location having the worst outcome (p < 0.001). In contrast, low-grade chondrosarcoma of appendicular skeleton could be treated safely by intralesional curettage. CONCLUSION: Histological type was significantly associated with the outcome of chondrosarcoma. For the conventional type, histologic grade and anatomical location predicted outcome, with high-grade with axial location having the worst outcome.
Chondrosarcoma* ; Curettage ; Follow-Up Studies ; Humans ; Pelvis ; Prognosis ; Recurrence ; Retrospective Studies ; Skeleton

There are few reports on the surgical treatment of secondary malignancy arising from an osteochondroma on the lateral side of the proximal tibia. From March 2008 to December 2011, 3 patients were treated for a secondary chondrosarcoma from an osteochondroma of the proximal tibia involving the fibula. The operative procedure can be summed up as follows: (1) resection of the tumor including the fibula; (2) preservation of the peroneal nerve and the fibular head; and (3) arthrodesis of the proximal tibiofibular joint. Serial radiological studies showed successful fusion in the proximal tibiofibular joint in all patients. The Musculoskeletal Tumor Society functional scores were excellent in all 3 patients. No patients showed instability of the ipsilateral knee joint in any direction. All 3 patients could return to sports activities. Until the last follow-up, there was no evidence of disease recurrence. We suggest that the operative procedure described in this article would provide satisfactory oncological and functional outcomes.
Arthrodesis ; Chondrosarcoma* ; Fibula* ; Follow-Up Studies ; Head ; Humans ; Joints ; Knee Joint ; Osteochondroma* ; Peroneal Nerve ; Recurrence ; Return to Sport ; Surgical Procedures, Operative ; Tibia*