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Purpose: The Japanese Musculoskeletal Oncology Group have developed an original prosthesis called the Kyocera Modular Limb Salvage system (KMLS system). This prosthesis has a semi-rotating hinge joint and is particularly designed for people with an Asian body type. The metallic parts of the prosthesis are made entirely of titanium alloy. The purpose of this study is to evaluate the clinical outcomes of treatment using this system following tumour resection of primary bone sarcoma of the distal femur., Methods: Between 2002 and 2010, 82 patients with primary bone sarcomas of the distal femur were treated. Seventeen patients underwent stem cementation, while 65 patients were treated with cementless prostheses. The mean follow-up period after surgery was 61 months., Results: Complications were observed in 28 of the 82 patients. Forty-one complications occurred in these 28 patients. Thirteen prostheses (16%) required revision surgery due to complications, including five cases of stem breakage, three deep infections, three cases of aseptic loosening, one case of displacement of the shaft cap and one case of breakage of the tibial tray. The five-year overall prosthetic survival rate was 80.0%. Four of the 82 patients underwent subsequent amputation due to local recurrence. The five-year limb salvage rate was 94.5%. The mean function score according to the scoring system of the Musculoskeletal Tumour Society was 21.8 points (72.5%)., Conclusions: Although further follow-up is required to determine the performance, this prosthesis is considered to be satisfactory for reconstruction of the distal femur after resection of bone sarcoma.

The aim of the present study was to determine whether serum high-sensitivity CRP (hs-CRP) levels can be used to predict the differentiation of benign soft tissue tumors and soft tissue sarcomas (STS) and whether there are any links between increased hs-CRP levels and patients' characteristics. Serum samples were collected from 14 healthy subjects, 35 patients with benign soft tissue tumors and 60 patients with STS. The Hs-CRP levels in the patients with STS were statistically higher than those observed in patients with benign soft tissue tumors (p<0.0001) and control subjects (p<0.0001). There were no significant differences in the hs-CRP levels between patients with benign soft tissue tumors and control subjects (p=0.16). In the receiver operating characteristic analysis, a value of 0.95 μg/ml was found to be an appropriate threshold for identifying patients at-risk for STS. The area under the curve was 0.747. The serum hs-CRP level exhibited a sensitivity and specificity STS of 50% and 94.3%, respectively, for identifying. The current analyses showed that an elevated hs-CRP level is associated with the presence of STS and may, therefore, be used as an additional marker for the differential diagnosis of soft tissue tumors.

Background: The incidence of sarcoma diagnosed in the elderly population may be rising due to the increasing life expectancy. The purpose of our study was to evaluate the efficacy of lung metastasectomy and radiofrequency (RF) ablation in elderly sarcoma patients (65 years or older) with lung metastases, compared with adult sarcoma patients younger than 65 years (20-64 years)., Materials and Methods: We retrospectively evaluated the clinical efficacy of metastasectomy and lung RF ablation in sarcoma patients with lung metastases., Results: Between 2001 and 2010, lung metastases were detected in 66 adult patients with musculoskeletal sarcomas. Twenty-five patients with lung metastasis were elderly. Twelve of the 25 patients were treated with lung metastasectomy and/or RF ablation. In contrast, 41 patients were adult patients younger than 65 years. Twenty of these 41 patients were treated with lung metastasectomy and/or RF ablation. The 1 and 3-year survival rates after initial treatment for lung metastases were 81.8% and 38.4% in 12 elderly patients, respectively. Compared with the control group, the survival rate in the elderly patients was not significantly different., Conclusion: We conclude that elderly sarcoma patients with lung metastases should always be considered for either metastasectomy or RF ablation.

The poliovirus receptor CD155, is essential for poliovirus to infect and induce death in neural cells. Recently, CD155 has been shown to be selectively expressed on certain types of tumor cells originating from the neural crest, including malignant glioma and neuroblastoma. However, the expression pattern of CD155 in soft tissue sarcoma has not been examined. Therefore, we first examined CD155 expression in sarcoma cell lines, and found the expression of both CD155 mRNA and protein in 12 soft and bone tissue sarcoma cell lines. Furthermore, we examined the effect of live attenuated poliovirus (LAPV) on 6 bone and soft tissue sarcoma cell lines in vitro, and found that LAPV induced apoptosis by activating caspases 7 and 3 in all of these cell lines. Furthermore, in BALB/c nu/nu mice xenotransplanted with HT1080 fibrosarcoma cells, administration of live attenuated poliovirus caused growth suppression of the tumors. These results suggest that oncolytic therapy using a LAPV may represent a new option for the treatment of bone and soft tissue sarcomas.

During the past 20 years, we have found that acridine orange (AO) selectively accumulates in musculoskeletal sarcomas in vivo or exerts selective cytocidal effects against sarcoma cells in vitro after illumination of the tumor cells with visible light or irradiation of the cells with low-dose X-rays. Based on the data obtained from basic research, we have employed reduction surgery followed by photo- or radiodynamic therapy using AO (AO-PDT & RDT) in 71 patients with musculoskeletal sarcomas, in an attempt to maintain excellent limb function in the patients. We have obtained good local control rates and remarkably better limb functions with this approach as compared to the results obtained with the conventional wide resection surgery. Our basic research demonstrated that AO accumulates densely in intracellular acidic vesicles, especially lysosomes, in an acidity-dependent manner. In cancer cells that proliferate under hypoxic conditions or with Warburg's effect, active glycolysis produces an enormous number of protons, which are released by the cells via proton pumps into the extracellular fluid or lysosomes to maintain a neutral pH of the cytosolic fluid. Cancer cells contain many strongly acidic lysosomes of large sizes; therefore, AO shows marked and prolonged accumulation in the acidic lysosomes of cancer cells. Photon energy excites the AO resulting in the production of activated oxygen species, which oxidize the fatty acids of the lysosomal membrane, resulting in the leakage of lysosomal enzymes and protons, followed by apoptosis of the cancer cells. Based on these observations, we conclude that AO-PDT & RDT target acidic vesicles, especially the lysosomes, in cancer cells, to exhibit selective anti-cancer cell activity. Therefore, it is suggested that AO excited by photon energy has excellent potential as an anticancer "Magic Bullet".

Background: Malignant soft tissue tumors of the foot are extremely rare and thus can be prematurely excised without appropriate preoperative evaluation. The present study compares adverse effects between unplanned and planned surgical excisions., Methods: We retrospectively reviewed the clinical records, radiographs, pathology reports and pathological specimens of 14 consecutive patients with soft tissue sarcoma of the foot among 592 with sarcomas between 1973 and 2009. We then compared the incidence and clinical outcomes after unplanned (UT; n = 5) and planned (PT; n = 9) surgical excisions of foot sarcomas., Results: The most frequent diagnosis was synovial sarcoma (n = 4; 28.6%). The overall 5-year survival rates of the PT and UT groups were 65.6% and 60.0%, respectively, and the event-free 5-year survival rates were 63.5% and 40.0%, respectively. Event-free and overall survival rates did not significantly differ between the two groups. However, tumors were significantly larger in the PT group than in the UT group (p < 0.05)., Conclusions: Unplanned resection lead to a relatively worse prognosis and a likelihood of recurrence despite additional resections. We recommend that soft tumors of the foot should only be excised after appropriate preoperative evaluation regardless of the size of the tumor.

Background and Objectives: The KYOCERA Physio Hinge Total Knee System Type III (PHKIII) was developed to reconstruct bony defects of the distal femur. The PHKIII is originative in that the metallic parts are fully made of titanium alloy, and this prosthesis has a unique semi-rotating hinge joint and was designed especially for people with the Asian physical body-type. The clinical outcomes of the PHKIII after the resection of musculoskeletal tumors of the distal femur were evaluated., Methods: There were 41 males and 28 females with a median age of 48-years. The median duration of follow-up was 57 months., Results: Eleven early complications and 37 late complications were observed, including 10 recurrences, 7 deep infections, 7 aseptic loosenings, 4 stem breakages, 4 displacements of shaft cap, and one wear of rotation sleeve. Twenty four prosthesis (35%) required a secondary operation because of complications. The five-year overall prosthetic survival rates, -prosthetic survival rate without aseptic loosening, and -limbs preservation rate were 85%, 90%, and 86%, respectively. The mean functional score according to the classification system of the Musculoskeletal Tumor Society was 20.5 points (68%)., Conclusions: Although continuous follow-up is required, reconstructions using PHKIII are considered to achieve more acceptable functional results., (Copyright © 2010 Wiley-Liss, Inc.)

Background and Objectives: We recently developed and established a new surgical therapy combining photodynamic surgery and radiodynamic therapy using acridine orange (AO) therapy after marginal or intralesional tumor resection, providing excellent limb function to sarcoma patients. The present study evaluated local recurrence rate and limb function using Disability of Arm, Shoulder, and Hand (DASH) score of patients with primary musculoskeletal sarcoma around the forearm treated with AO therapy, compared to that of patients treated with conventional wide resection., Methods: Subjects were 18 patients with primary musculoskeletal sarcoma around the forearm and treated with AO therapy (AO: n = 8) after marginal or intralesional resection, or conventional wide resection followed by limb reconstruction surgery (WR: n = 10)., Results: Mean age of the 18 patients was 45 years, and mean durations of follow-up for Groups AO and WR were 67 and 74.1 months. Local recurrence rates for AO and WR were 12.5% and 20% (P = 0.63), DASH disability scores were 3.9 and 21 (P = 0.04), and 5-year survival rates were 100% and 90% (P = 0.40), respectively., Conclusions: AO therapy offers maintenance of excellent upper limb function and inhibition of local tumor recurrence, representing a useful modality for limb salvage surgery in patients with sarcoma around the forearm., (2010 Wiley-Liss, Inc.)

Background: The authors retrospectively evaluated the impact of lung radiofrequency (RF) ablation on survival in patients with lung metastases from musculoskeletal sarcomas., Methods: Lung RF ablation was done under the real-time computed tomography (CT) fluoroscopy. Safety, local tumor progression, and survival were evaluated in 2 institutions., Results: Lung RF ablation was performed in 20 consecutive patients. The mean maximum tumor diameter was 14 +/- 9 mm (range, 5-40 mm) and the mean tumor number 7 +/- 6 (range, 1-18) per patient. Pneumothorax requiring chest tube placement developed in 24 of 63 RF sessions (38%). During the mean follow-up period of 18 months (range, 7 months to 54 months), 9 of 20 patients died of lung tumor progression. The 1- and 3-year survival rates from RF ablation were 58% (95% confidence interval [CI], 33.3-82.6%) and 29% (95% CI, 0-59.9%) with a median survival time of 12.9 months in all patients. Ablation of all lung tumors was the only significantly better prognostic factors in both the univariate analysis and the multivariate analyses. The 1- and 3-year survival rates were 88.9% (95% CI, 69.3%-100%) and 59.2% (95% CI, 10.2%-100%) in 11 patients with complete tumor ablation., Conclusions: Lung RF ablation is a safe and useful therapeutic option for selected patients. (R#1) Prognostic factors identified in our study will help to stratify those patients who may benefit from lung RF ablation.

Small pulmonary nodules in patients with sarcoma are problematic, because it is difficult to distinguish such small metastatic nodules from benign. The purpose of this study was to establish management guidelines for such small pulmonary nodules in patients with sarcoma. Pulmonary nodules were detected in 70 of 206 patients with sarcoma. About 55 patients were classified as having pulmonary metastasis. Seventeen of these 55 patients with pulmonary metastases were excluded from the imaging review because they did not undergo the required imaging examination. This study reviewed 38 patients with metastatic nodules and 15 patients with benign nodules. A statistically significant relationship was observed between the size of the nodules and final clinical decision. The patients with pulmonary nodules which did not exceed 5 mm in size showed significantly better cumulative overall survival rate after the detection of pulmonary nodules than those with larger nodules (5-years: 58.4 vs. 20.4%). There was no significant difference in the overall survival rate between the patients with smaller pulmonary benign lesions which did not exceed 5 mm in size and those with a normal chest CT (5-years: 92.3 vs. 85.3%). The only factor to diagnose in a metastatic pulmonary lesion is the size of the nodules. If the nodule remains < or = 5 mm in size for more than 6 months, the nodule will be a benign lesion. On the contrary, if the nodule becomes larger than 5 mm within 6 months, a surgical excision of the nodules is recommended.

Purpose: The usefulness of limb salvage surgery for distal lower leg sarcoma remains controversial. We analyzed the long-term prognosis, limb function, and complications after limb salvage treatment of patients with distal lower leg sarcoma., Methods: Ten patients treated with limb salvage surgery for primary distal lower leg sarcoma were retrospectively reviewed. The median follow-up period after the first operation was 9.0 years. We performed three types of reconstructive techniques for the skeletal defect after a wide resection, including (1) arthrodesis with a combination of autograft and intraoperative autoclaved tumor bone graft in two patients, or allograft in one patient, (2) ankle joint preserving surgery using intraoperative extracorporeal irradiated tumor bone graft in five patients, and (3) prosthesis in two patients., Results: The overall survival rate was 80%. The 5-year disease-free survival was 80%. The rate of limb preservation at the final follow-up was 90%. The mean functional score according to the scoring system of the Musculoskeletal Tumor Society was 88% at the final follow-up. Postoperative complications occurred in seven patients. Skin trouble occurred in three patients, infectious non-union in one patient, fracture in three patients, and loosening of prosthesis in one patient., Conclusions: Despite the high rate of complications, patients treated with limb salvage surgery for the distal lower leg sarcoma revealed excellent final functional results without impairing the oncologic results. Limb salvage surgery is therefore considered to be an effective treatment option for distal lower leg sarcoma when adequate informed consent can be obtained from the patient.

Background: To maintain excellent limb function after tumor resection in patients with high-grade malignant sarcomas, we developed and established a new surgical adjuvant therapy using acridine orange (AO) after intra-lesional or marginal resection while sparing normal tissues of major nerves, vessels or bones adjacent to the tumor., Method: Our AO therapy procedure was combined with photodynamic surgery (PDS), photodynamic therapy (PDT) and radiodynamic therapy (RDT). In this study, 26 patients with primary high-grade soft tissue sarcomas were treated with AO therapy., Result: Results showed a low local recurrence rate (7.7%) and good local recurrence-free rate (88%) after AO therapy. Limb function of all patients was maintained at 100% of ISOLS criteria., Conclusion: Based on these results, we concluded that AO therapy is useful for local control after margin-positive tumor resection and for preserving excellent limb function in patients with high-grade soft tissue sarcomas., ((c) 2008 Wiley-Liss, Inc.)

Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that supports the adaptation of human cancer cells to hypoxia and tumor growth and progression. The overexpression of HIF-1alpha protein has been reported to be associated with a worse prognosis in various cancers. However, the expression of HIF-1alpha in soft-tissue sarcomas has not yet been characterized. The expression of HIF-1alpha protein was immunohistochemically determined in 49 specimens of soft-tissue sarcomas including malignant fibrous histiocytoma (29 patients), synovial sarcoma (12 patients), leiomyosarcoma (four patients), and malignant peripheral nerve sheath tumors (four patients). The 49 samples consisted of 40 primary lesions and nine local recurrences. An immunohistochemical analysis showed the nuclear accumulation of HIF-1alpha protein in 35 (71.4%) samples. The expression of HIF-1alpha was negative in 14 (28.6%) cases, weak in nine (18.4%), moderate in 17 (35.4%), and strong in nine (18.4%). The patients with a strong or moderate expression of HIF-1alpha had a significantly shorter overall survival rate in comparison with those with a weak or negative expression in a univariate analysis (P = 0.029; log-rank test) and multivariate analysis (P = 0.018). This is the first report that demonstrated an overexpression of HIF-1alpha protein to be an independent prognostic factor for soft-tissue sarcomas.

Most patients with musculoskeletal sarcoma do not recover satisfactory limb function after limb salvage surgery. To achieve satisfactory improvement of limb function, we developed a unique surgical modality of photodynamic therapy using acridine orange (AO-PDT) and clinically applied it to patients with musculoskeletal sarcomas. Ten patients with primary musculoskeletal sarcomas were enrolled in the study. Of these, 6 had primary malignant soft tissue sarcoma and 4 had primary malignant bone tumor. In the AO-PDT procedure, intralesional or partially marginal tumor excision was initially conducted and microscopic curettage of the remnant tumor, which emitted green fluorescence under blue excitation after local administration of 1microg/ml AO solution, was performed using a fluorescence surgical microscope. Subsequently, blue light illuminated there for 10 minutes. The surgical wound was closed, followed by immediate X-ray irradiation of the resected area with 5 Gy in 5 out of 10 patients to enhance the effect of AO-PDT. The follow-up of the patients ranged from 24 to 48 months. All the patients (AO-PDT alone: 5, AO-PDT with 5-Gy radiation: 5) are alive; only one patient showed local recurrence of the tumor. The recurrence rate was 10%. None of the 5 patients treated by AO-PDT with radiation developed local tumor recurrence. The limb function in all the patients, except for one, recovered to the level before surgery. None of the patients clinically showed any local or systemic complications. AO-PDT may be a promising new limb salvage modality for preservation of excellent limb function in patients with musculoskeletal sarcoma.

Background: Telomerase is a ribonucleoprotein enzyme that extends telomere specific repeats on the ends of chromosomes. Telomerase activity has been detected frequently in various types of human tumors and has been associated with cell immortality and oncogenesis. Human telomerase reverse transcriptase (hTERT), a telomerase catalytic subunit, reportedly regulates telomerase activity. Little is known about telomerase activity and hTERT mRNA expression in soft tissue tumors. The objective of this study was to clarify the correlation between these two parameters and clinical aggressiveness in soft tissue tumors., Methods: In 41 surgically resected soft tissue tumors, telomerase activity was measured by the fluorescence-based telomeric repeat-amplification protocol and hTERT mRNA expression was determined by real-time polymerase chain reaction., Results: Telomerase activity was detected in 52% of sarcomas and in none of the benign soft tissue tumors (P < 0.05). Telomerase activity was found in 77% of 13 locally recurrent sarcomas and in 89% of 9 sarcomas with distant metastasis. The frequency of the presence of telomerase activity in those tumors was significantly greater compared with the frequency of telomerase activity in the other sarcomas (P < 0.05 and P < 0.01, respectively). All telomerase positive sarcomas expressed hTERT mRNA. The mean level of hTERT mRNA expression in sarcomas was significantly greater compared with the mean hTERT mRNA expression level in benign tumors (P < 0.05) and in locally recurrent sarcomas compared with primary sarcomas (P < 0.001)., Conclusions: The results of the current study suggest that the detection of telomerase activity and the level of hTERT mRNA expression are useful markers for evaluating the clinical aggressiveness in soft tissue tumors., (Copyright 2002 American Cancer Society.)

The article reports on the study that evaluates the impact of lung radiofrequency (RF) ablation on survival in patients with lung metastases from musculoskeletal sarcomas. It indicates that ablation of all lung tumors was significantly better prognostic factors in both the univariate analysis and the multivariate analyses. It reveals that lung RF ablation is a safe and useful therapeutic option for selected patients.