Search

Background: The modified Glasgow prognostic score (mGPS) is a reliable system for identifying patients at high risk of death among patients with soft tissue sarcoma (STS). The scoring systems use a combination of C-reactive protein (CRP) and albumin levels. Although patients with high-grade STS are at risk of metastasis and death, even if their mGPS is 0, the prognostic indicators in these patients are unknown. Therefore, we investigated useful prognostic indicators for survival and the development of metastasis in patients with high-grade STS and an mGPS of 0., Methods: One hundred and four patients with CRP and albumin levels of <1.0 mg/dl and >3.5 g/dl, respectively, indicating an mGPS of 0, were included. The mean follow-up period was 79 months., Results: The 5-year disease-specific survival (DSS) rate was 79.2%. Cox proportional analysis showed that tumor size and absolute neutrophil count (ANC) were prognostic variables in multivariate analyses. Patients with higher ANC (ANC>3370/μl) had a worse DSS than those with lower ANC. The 5-year DSS was 74.7% vs. 91.7%, respectively (p = 0.0207). The 5-year metastasis-free survival was 67.2%. Tumor size and ANC remained significant variables for predicting the development of metastasis in the multivariate analysis. Patients with higher ANC had a worse metastasis-free survival than those with lower ANC. The 5-year metastasis-free survival was 59.5% vs. 87.3%, respectively (p = 0.00269)., Conclusions: When patients with high-grade STS have an mGPS of 0, the ANC and tumor size should be carefully evaluated. A higher neutrophil count and larger tumor size may increase the risk of metastasis development., Competing Interests: Declaration of competing interest There was no conflict of interest in the present study., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Recently, we identified artifactual hypoglycemia in patients with soft tissue sarcoma (STS) who received pegfilgrastim-supported chemotherapy. In the present study, we measured white blood cell count and fasting blood glucose levels after the administration of pegfilgrastim in patients with STS and showed the relationship between artifactual hypoglycemia and white blood cell count., Patients: A total of 19 patients were included in this study. The mean age of the patients was 54 years. They received chemotherapy and administration of pegfilgrastim. Pegfilgrastim was injected subcutaneously 48 h after chemotherapy. No patient had a history of diabetes mellitus., Results: Fifty-nine cycles were administered to 19 patients. One hundred and twenty-eight samples were obtained within one week after the of pegfilgrastim administration. Hypoglycemia was observed in 38 of the 13 patients. There were no symptoms of hypoglycemia in any patient. The white blood cell count in samples from patients with hypoglycemia was significantly higher than that in samples without hypoglycemia (p < 0.001). The median white blood cell count in samples with hypoglycemia was 29,415 and 3420 in samples without hypoglycemia. Age, sex, body mass index, performance status, and red blood cell count were not associated with hypoglycemia. White blood cell count was strongly negatively correlated with fasting blood glucose levels (Pearson's r: 0.786, 95% confidence interval: 0.844-0.709, p < 0.001). Of the 38 samples with hypoglycemia, 32 were measured within 2 days after pegfilgrastim administration., Conclusion: If a lack of symptoms due to hypoglycemia and leukocytes is confirmed, physicians should wait and identify the normalization of the level of glucose according to the neutrophil nadir following temporal leukocytes, which prevents further invasive examination for hypoglycemia., Competing Interests: Declaration of competing interest There was no conflict of interest in the present study., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Prompt histopathological diagnosis with accuracy is required for soft tissue sarcomas (STSs) which are still challenging. In addition, the advances in artificial intelligence (AI) along with the development of pathology slides digitization may empower the demand for the prediction of behavior of STSs. In this article, we explored the application of deep learning for prediction of prognosis from histopathological images in patients with STS., Methods: Our retrospective study included a total of 35 histopathological slides from patients with STS. We trained Inception v3 which is proposed method of convolutional neural network based survivability estimation. F1 score which identify the accuracy and area under the receiver operating characteristic curve (AUC) served as main outcome measures from a 4-fold validation., Results: The cohort included 35 patients with a mean age of 64 years, and the mean follow-up period was 34 months (2-66 months). Our deep learning method achieved AUC of 0.974 and an accuracy of 91.9% in predicting overall survival. Concerning with the prediction of metastasis-free survival, the accuracy was 84.2% with the AUC of 0.852., Conclusion: AI might be used to help pathologists with accurate prognosis prediction. This study could substantially improve the clinical management of patients with STS., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: This multicenter retrospective study aimed to clarify the surgical and oncological outcomes of patients with high-grade soft tissue sarcoma (STS) who underwent prosthetic replacement reconstruction after lower extremity tumor resection., Patients and Methods: We retrospectively collected the data of 27 patients with high-grade STS. The mean follow-up duration after prosthetic replacement was 44.7 months., Results: The mean age at surgery was 63 years. The mean tumor size was 16 cm. For reconstruction, proximal femur replacement was performed in 15 patients, distal femur replacement in six, and total femur replacement in six. The major complications were infections in nine patients and aseptic loosening in four. Nine patients developed local recurrence. The cause of revision surgery was infection in five patients, aseptic loosening in three, and metal allergy in one. The 5-year prosthetic survival rate was 51.1%. At the final follow-up, amputation was performed in five patients. The 5-year limb salvage rate was 76.8%. The mean functional score of the 25 patients who could be assessed was 16.0 (53%). Of the 27 patients, five were excluded from the survival analysis because they underwent prosthetic replacement for local recurrence. The 5-year overall survival rate in the remaining 22 patients was 45.3%., Conclusion: We identified a high rate of surgical complications and poor survival in patients with high-grade STS who underwent tumor resection and reconstruction using prosthetic replacement of the lower extremities, although limb salvage was achieved in 81.5% of the patients. Careful follow-up is needed for surgical complications and oncological events after surgery., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Coagulation and fibrinolysis are distinct processes that are highly correlated. Cells control coagulation and fibrinolysis by expression of tissue factor and urokinase-type plasminogen activator receptor on their surface. Tumor cells express these proteins, adjust their microenvironment and induce tumor exacerbation. We hypothesized that the expression of plasma markers for coagulation and fibrinolysis in patients with soft tissue sarcomas (STSs) was dependent on the level of tumor malignancy. To elucidate which markers are predictive of recurrence, metastasis and prognosis, coagulation or fibrinolysis, we analyzed the correlation between plasma levels of thrombin-antithrombin III complex (TAT), soluble fibrin (SF), plasmin-α2 plasmin inhibitor complex (PIC), D-dimer (DD) and clinical parameters in patients with STSs., Methods: TAT, SF, PIC or DD were measured in pre-treatment blood samples from 64 patients with primary STSs and analyzed with clinicopathological parameters, and 5-year recurrence free survival (RFS), 5-year metastasis free survival (MFS) and 5-year overall survival (OS) were evaluated., Results: The metastasis group had significantly higher DD (p = 0.0394), PIC (p = 0.00532) and SF (p = 0.00249) concentrations than the group without metastasis. The group that died of disease showed significantly higher DD (p = 0.00105), PIC (p = 0.000542), SF (p = 0.000126) and TAT (p = 0.0373) than surviving patients. By dividing the patients into low and high groups, the group with high DD, PIC, SF and TAT showed significantly lower 5-year MFS and 5-year OS than the corresponding low group. Furthermore, in multivariate COX proportional hazard analysis of continuous variables for 5-year MFS, only PIC was found to be a significant factor (HR: 2.14)., Conclusion: Fibrinolysis was better than coagulation at reflecting the disease condition of patients with STS. Notably, PIC levels ≥ 1.1 can not only predict the risk of metastasis and poor prognosis, but also increasing PIC levels correspond to further increases in risks of metastasis and poor prognosis., (© 2022. The Author(s).)

Purpose of Review: Surgical resection is the standard treatment for localized soft tissue sarcoma (STS), while systemic chemotherapy for advanced STS may be considered. However, less aggressive treatment is often administered to elderly patients with STS. Undertreatment may compromise the cure rate and survival of these individuals. We review the literatures and emphasize the importance of standard treatment for STS in elderly patients., Recent Findings: The outcome of surgical resection of STS in older individuals is comparable to that of younger ones, as long as patients are selected based on American Society of Anesthesiologists Physical Status (ASA-PS). Likewise, systemic treatment may prove beneficial as long as the risk of complications is estimated with a geriatric assessment. Elderly patients with STS benefit from standard treatment as long as the risks of surgical and systemic complications are assessed respectively with the ASA-PS and GA. Novel clinical trials with broader eligibility criteria are also necessary for elderly patients because of the increasing population of the elderly patients in the future., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study aimed to elucidate the clinical outcomes of patients with small (≤5 cm) high-grade soft tissue sarcoma, who underwent unplanned excision with positive surgical margin, using data from the Bone and Soft Tissue Tumor registry in Japan., Methods: We examined 174 patients (101 males and 73 females; mean age, 59 years) with primary non-metastatic soft tissue sarcoma. The tumor size was ≤5 cm, and tumor histological grade was high in all patients. The mean follow-up duration was 50 months., Results: Unplanned excision with R1 and R2 margins was reported in 115 (66%) and 59 patients (34%), respectively. After unplanned excision, immediate additional excision was performed in 154 patients, whereas no additional excision was performed in the remaining 20. Of the 154 patients who underwent additional excision, wide surgical margin resection was achieved in 140 patients, while marginal and intralesional resections were achieved in 10 and 3 patients, respectively. Additionally, 93 patients (60%) underwent reconstruction after additional excision. During the last follow-up, 8 patients died of the disease, 22 developed distant metastasis, and 14 reported local recurrence. The 5-year disease-specific survival rate and 5-year metastasis-free survival rate was 93.5% and 85%, respectively. Tumor depth and additional excision after unplanned excision showed statistical significance in the multivariate analysis. The 5-year metastasis-free survival rate was 89.1% in patients with additional excision and 39.2% in those without. Univariate analysis showed an association between additional excision and local control. The 5-year local recurrence-free survival was significantly worse in patients without additional excision after unplanned excision (52.6%) than in those with additional excision (92.8%)., Conclusion: If unplanned excision is performed in patients with small high-grade soft tissue sarcoma, additional excision is recommended for preventing metastasis, along with necessary preparations for reconstruction., Competing Interests: Conflict of interest There was no conflict of interest in the present study., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Due to their rarity, soft tissue sarcomas (STS)s are often treated surgically as unplanned excisions (UE)s before referral to specialists. The Bone and Soft Tissue Tumor (BSTT) registry is a nationwide, organ-specific cancer registry for bone and soft-tissue tumors in Japan. The aim of this study was to elucidate the incidence and risk factors for UEs using data from the BSTT registry., Methods: Our study comprised 8761 patients with STS including 4826 males and 3935 females, with a mean age of 59 years (range, 0-105 years). Patients were classified into primary STS and UE groups., Results: Superficial and deep tumors were found in 2533 and 6120 patients, respectively. The mean STS size was 8.6 cm (range, 0.2-49 cm). We identified 6610 patients with high-grade, and 1758 patients with low-grade STS. Of the total 8761 patients, 7770 patients had primary STSs, whereas 991 patients were referred after undergoing UE. The UE mean incidence rate over 11 years was 11.3%. The UE incidence rates for leiomyosarcoma (LMS) (odds ratio [OR] = 1.75, p < 0.0001), fibrosarcoma (FS) (OR = 2.28, p < 0.0001), and epithelioid sarcoma (OR = 1.82, p = 0.01) were higher than the mean UE incidence rate (11.3%). Of 757 patients who underwent UE, 354 (47%) patients had superficial (≤5 cm) STSs, whereas 156 (20.6%) of patients had deep STSs (>5 cm) (p < 0.0001). Logistic regression analysis revealed that UE was frequently associated with males and small, superficial, and trunk STSs., Conclusions: In the present study, the mean UE incidence rate (11.3%) was significantly different from the individual UE incidence rates of histological diagnoses suggesting that surgeons should consider STS, even with small tumors. Continuous education during training for medical students and surgeons is essential to ensure awareness and correct diagnostic procedures for STS., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Soft tissue sarcomas are a diverse group of rare malignant tumours, mostly occurring in the lower extremities. Amputations are necessary for achieving local control when the soft tissue sarcomas are too large and/or have neurovascular involvement. Patients who require amputation have a poorer prognosis than those who undergo limb-salvage surgery., Patients and Methods: We investigated the tumour characteristics and the clinical outcomes in 55 patients with primary soft tissue sarcomas, who underwent amputation. We excluded patients with amputation performed distal to the wrist or ankle joints and those with recurrent soft tissue sarcomas., Results: The mean tumour size was 11.1 cm. Hip disarticulation was performed in 6 patients, 20 underwent above the knee amputation, 8 underwent knee disarticulation and 12 underwent below the knee amputation. Shoulder disarticulation was performed in three patients, five underwent above the elbow amputation, and one underwent below the elbow amputation. The 5-year disease-specific survival rate was 52.8%. The 5-year recurrence-free survival rate and 5-year metastasis-free survival rates were 90.1% and 38.5%, respectively. Larger tumour size, age and the distant metastases at first presentation were predictors of poor prognosis for survival in multivariate analysis. Twenty-eight patients could walk using artificial limbs. The level of amputation (above versus below the knee) showed a significant difference in achieving independent gait., Conclusion: Amputation is a useful treatment option for achieving local control in patients with large soft tissue sarcomas. Patients had an opportunity of walking, especially for those who underwent below the knee amputation., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Patients with soft-tissue sarcoma (STS) who undergo unplanned excision (UE) are reported to have worse outcomes than those who undergo planned excision (PE). However, others have reported that patients who undergo UE may have similar or improved outcomes. These discrepancies are likely to be due to differences in characteristics between the two groups of patients. The aim of the study is to compare patients who underwent UE and PE using propensity score matching, by analyzing data from the Japanese Bone and Soft Tissue Tumor (BSTT) registry., Methods: Data from 2006 to 2016 was obtained from the BSTT registry. Only patients with STS of the limb were included in the study. Patients with distant metastasis at the initial presentation and patients with dermatofibrosarcoma protuberans and well-differentiated liposarcoma were excluded from the study., Results: A total of 4,483 patients with STS of the limb were identified before propensity score matching. There were 355 patients who underwent UE and 4,128 patients who underwent PE. The five-year disease-specific survival (DSS) rate was significantly better in the patients who received additional excision after UE than in those who underwent PE. There was no significant difference in local recurrence-free survival (LRFS) between the two groups. After propensity score matching, a new cohort of 355 patients was created for both PE and UE groups, in which baseline covariates were appropriately balanced. Reconstruction after tumour excision was frequently performed in patients who underwent additional excision after UE. There were no significant differences in DSS and LRFS between the patients who underwent PE and those who had an additional excision after UE., Conclusion: Using propensity score matching, patients with STS of the limb who underwent additional excision after UE did not experience higher mortality and local failure than those who underwent PE. Reconstruction may be necessary when additional excision is performed. Cite this article: Bone Joint J  2021;103-B(12):1809-1814.

Background: This study aimed to determine whether the prognostic nutritional index (PNI) can predict the prognosis in patients with soft-tissue sarcoma (STS) before treatment and to examine whether there is an association between PNI values and clinical characteristics., Patients and Methods: The data on 100 patients with primary STS were retrospectively reviewed. The cohort included 55 men and 45 women, with a mean age of 64 years. The mean follow-up duration was 41.7 months., Results: The median PNI was 51.35. The PNI was significantly inversely associated with tumor size, tumor grade, and age. We found that the PNI was a significant prognostic marker for disease-specific and event-free survival using univariate and multivariate analyses. Patients with a low PNI had poorer disease-specific and event-free survival than those with a high PNI., Conclusion: These results suggest that the PNI can be used as a prognostic marker in patients with STS., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: Synovial sarcoma is the most common soft tissue sarcomas among childhood and adolescents, accounting for 8-10% of all soft tissue sarcoma. Synovial sarcoma is considered a relatively chemosensitive tumor compared with other soft tissue sarcomas. However, the role of perioperative chemotherapy in synovial sarcoma remains controversial. The purpose of this systematic review is to evaluate the role of perioperative chemotherapy in childhood and adolescent patients with synovial sarcoma., Methods: We evaluated studies published between 1 January 1990 and 31 December 2017. The following databases were searched: MEDLINE, Cochrane database (via PubMed) and Ichushi (in Japanese)., Results: The search yielded 216 articles in English and Japanese. After the initial screening, based on the title and abstract, 160 articles were excluded. As a second screening, we then assessed the full text of the remaining 56 articles for eligibility. Finally, 10 articles were included in the systematic review. Surgical resection with R0 margin alone was recommended because of the excellent results of two prospective studies. Meta-analysis was performed using data from two retrospective studies of 261 patients. Perioperative chemotherapy did not have a significant effect on survival and event-free survival., Conclusions: We weakly do not recommend perioperative chemotherapy in patients with non-metastatic synovial sarcoma ≤ 5 cm when R0 resection is acquired. There was no consensus concerning the role of perioperative chemotherapy in patients with synovial sarcoma > 5 cm or those with ≤5 cm who undergo R1 or R2 resection., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: We investigated the clinical outcomes of reconstruction using the latissimus dorsi (LD) flap after resection of soft-tissue sarcoma., Materials and Methods: We analyzed 19 patients. Free LD flap was performed in 11 patients and pedicle flap in eight patients. The mean follow-up period after the surgery was 60 months., Results: The mean age at diagnosis was 57 years. The mean tumor size was 9.8 cm. The median size of the LD flap was 140 × 100 mm. The mean surgical duration and bleeding were 510 min and 602 mL, respectively. Complications included partial skin and soft-tissue necrosis (n = 3) and wound dehiscence (n = 2). No additional free flap was not necessary for the closure of the defect due to the complications. The longer surgical duration was significantly associated with wound complications (P = 0.048). The 5-year survival rate was 80.7%, and the local recurrence-free survival rate was 89.2%. Two patients developed local recurrence, while 6 patients developed metastasis. None of the patients had any restrictions of daily life., Conclusion: The LD flap after surgical tumor resection in patients with soft-tissue sarcoma was useful for the coverage of soft tissue.

Objective: To elucidate the correlation between expression of thrombomodulin (TM) mRNA from 83 benign soft tissue tumors or soft tissue sarcomas (STS) and clinicopathological parameters and to analyze the outcome of high-grade STS patients after 10 years., Methods: Total RNA was extracted from 83 primary soft tissue tumors (15 benign tumors, 68 STS). TM mRNA normalized to glyceraldehyde-3-phosphate dehydrogenase was measured with real-time quantitative polymerase chain reaction and compared to various clinicopathological parameters. The log-rank test and Cox proportional hazard analysis were used to evaluate recurrence-free survival, metastasis-free survival, and overall survival., Results: Thrombomodulin mRNA levels were not significantly different between benign tumors and STS. In STS, TM mRNA levels were not significantly different between histologically high-grade (n = 57) and low-grade (n = 11) tumors. Following analysis of high-grade STS at the 10-year follow-up, 21 patients had experienced a recurrence, 22 patients had experienced metastasis, and 23 patients had died of disease (DOD). TM levels were significantly higher in patients with metastasis or DOD patients. Receiver operating characteristic analysis for identifying 5-year and 10-year DOD determined the threshold for best sensitivity and specificity as 0.283. We divided patients into those with high (<0.283) and low (≤0.283) TM mRNA levels. Based on Kaplan-Meier analysis, a significant difference between the two groups was seen for recurrence-free survival (5 years: low = 76.6%, high = 53.1%, 10 years: low: 67.0%, high 39.8%, P = 0.0122) and metastasis-free survival (5 years: low = 86.3%, high = 40.2%, 10 years: low: 73.3%, high: 35.2%, P = 0.00023). Furthermore, the high TM group showed significantly worse prognosis than the low TM group (5 years: low = 90.1%, high = 42.3%, 10 years: low: 76.4%, high 31.3%, P = 0.00031). Thus, high levels of TM mRNA are associated with highly recurrent and metastatic potential and lead to poor prognosis. In multivariate Cox proportional hazard analysis, only high TM showed a significant difference in metastasis-free survival (hazard ratio: 4.33, 95% confidence interval 1.61-11.6, P = 0.00359) and overall survival (hazard ratio: 3.69, 95% confidence interval 1.49-10.5, P = 0.00569)., Conclusion: High levels of TM mRNA may be a significant predictor of recurrence, metastasis, and a poor outcome in STS patients after 10 years. TM is a candidate molecular marker and may be clinically useful for devising a therapeutic treatment strategy by prediction of prognosis., (© 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Introduction: The median survival time of patients with advanced soft tissue sarcoma (STS) is typically <12 months. Since 2012, physicians were able to administer second- and/or third-line treatment easily in Japan, following the approval of new drugs, namely, pazopanib, eribulin, and trabectedin. We investigated the real-life experience of adults with advanced STS who received systemic therapy after the approval of the aforementioned new drugs., Patients and Methods: We retrospectively evaluated 34 patients (median age: 66 years) with primary STS arising at the extremities/trunk or unresectable local and/or metastatic STS between 2012 and 2019. We evaluated the tumor response and patient survival after initial systemic treatment., Results: As first-line treatment, doxorubicin and ifosfamide and other drugs were administered to 7 and 27 patients, respectively. Of 31 patients with an evaluable tumor response, partial response was observed in 2 (6.5%) patients, and 16 (52%) patients showed stable disease at 8 weeks. The 1- and 2-year survival rates were 51.4% and 28.4%, respectively. The median overall survival (OS) time was 12.6 months. Tumor response to first-line therapy was related to patient prognosis., Conclusion: New drugs may be beneficial for patients with advanced STS. When patients cannot receive anthracycline-based chemotherapy because of a high risk of side effects, we believe that the aforementioned drugs may be administered as the first-line treatment., Competing Interests: We declare that we have no conflict of interest to declare in relation to this study., (© 2020 Nakamura et al.)

The soluble form of PD-L1 (sPD-L1) is related to a poor prognosis in various cancers. Comparisons of sPD-L1 and PD-L1 expressed on tumor cells in soft tissue tumor patients have not been reported. The purpose of this study was to analyze serum sPD-L1 and PD-L1 levels in soft tissue tumor patients. A total of 135 patients with primary soft tissue tumors were enrolled in this study. The sPD-L1 level was quantitatively measured by enzyme immunoassay, and PD-L1 expression on high grade sarcoma cells was analyzed immunohistologically. There were no significant differences in sPD-L1 levels between benign (48) and soft tissue sarcoma (STS) patients (87). In STS, the high sPD-L1 (>44.26 pg/mL) group had significantly lower metastasis-free survival (MS) and lower overall survival (OS) than the low sPD-L1 group (≤44.26 pg/mL) at 5 years using the log-rank test. On multivariate Cox proportional hazard analysis, the high sPD-L1 group had significant differences in MS and OS compared to the low sPD-L1 group. Between positive and negative immunostaining groups, recurrence-free survival (RS), MS, and OS were not significantly different. No correlation was found between immunostaining and sPD-L1 with the Kappa coefficient. The sPD-L1 concentration could predict future metastasis and prognosis in STS patients. High sPD-L1 in STS patients may be a target for treatment with checkpoint inhibitors.

Pazopanib, a targeted molecular drug, has been proposed as an effective treatment for soft tissue tumour and as a novel adjuvant therapy. There has been a paradoxical concern that wound healing could be inhibited by its anti-angiogenic properties, especially in reconstructive surgery. This paper reports on a 28-year-old woman who underwent flap surgery due to a skin and soft tissue injury after an effective treatment with pazopanib for refractory epithelioid sarcoma. The flap survived without any complication in off-periods of pazopanib for four weeks before and after the surgery, although it is only recommended that the washout periods of pazopanib commence at least seven days before scheduled surgery.

Background/aim: The aim of the present study was to determine whether serum lactate dehydrogenase (LDH) levels before treatment could predict the disease-specific and event-free survival in adult patients with STS., Patients and Methods: A total of 142 adult patients with primary STS were reviewed. The average follow-up was 73 months with a minimum 2-year follow-up., Results: Age was significantly associated with LDH. Tumor grade, sex, tumor size, tumor depth, CRP levels, Hb levels and albumin levels were not related. LDH levels were not significantly related to the oncological outcome including disease-specific survival and event-free survival in multivariate analysis. CRP levels were significantly related to the oncological outcome including event-free survival., Conclusion: Elevated LDH levels prior to initial treatment were not found to be a poor prognostic factor of oncological outcome in adult STS, in both the univariate and multivariate analyses. We recommend routine measurement of the CRP levels for predicting oncological outcome., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: We analyzed the process of healing at osteotomy sites and timing of achievement of full weight-bearing in sarcoma patients who underwent hemicortical or intercalary reconstruction using the extracorporeal irradiated autologous bone graft technique., Patients and Methods: We studied 10 patients who had undergone tumor resection and reconstruction with hemicortical extracorporeal irradiated autologous bone graft at mid-shaft femur or tibia. The control group consisted of 30 patients who received the reconstruction using intercalary bone graft., Results: Full weight-bearing was achieved in all 10 patients at a median time of 4.8 months. Function was excellent in all patients. When comparing the clinical outcome among the patients who received intercalary and hemicortical grafts, the duration to full weight-bearing achievement in patients who received hemicortical graft was shorter than that in those with intercalary graft., Conclusion: Early full weight-bearing may be achieved in patients undergoing hemicortical resection and reconstruction using extracorporeal irradiated autologous bone graft., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The efficacy and safety of eribulin in Japanese patients with advanced soft-tissue sarcomas (STS) have not been evaluated in a large-scale cohort study. Thus, we aimed to investigate the clinical outcome of 82 Japanese patients with STS receiving eribulin across multiple study centers retrospectively. Of 82 STS patients receiving eribulin treatment, 13 were treated for locally unresectable tumor, 46 for metastasis, and 23 for both. The primary endpoint of this study was to evaluate the efficacy of eribulin against STS. The median age was 60 years. Thirty-seven were diagnosed with L-sarcoma (leiomyosarcoma or liposarcoma) and 45 had non-L-sarcoma. The median progression-free survival (PFS) for all patients was 2.7 months, with 3.4 months in those with L-sarcoma and 2.2 months in those with non-L-sarcoma. Patients with L-sarcoma showed a better PFS than those with non-L-sarcoma. Overall, the median survival time was 11.1 months, and 12.3 months and 7.9 months in patients with L-sarcoma and non-L-sarcoma, respectively; however, there was no significant differences between the groups. The prognostic significance of PS = 0 and both existence of local and metastatic STS was evaluated by multivariate analysis. We also evaluated the overall survival (OS) in patients with undifferentiated pleomorphic sarcoma (UPS) and other non-L-sarcomas. Patients with UPS had better OS than those with the other non-L-sarcomas. In conclusion, there was a significant difference in PFS between patients with L-sarcoma and non-L-sarcoma following treatment with eribulin. The anti-tumor potential of eribulin was evident in patients with UPS.

Purpose: Soft tissue sarcomas (STSs) of the thigh's adductor compartment frequently attain a large size before clinical presentation and displace the major neurovascular and lymph structures. We aimed to elucidate the clinical outcome in patients with STS of the thigh's adductor compartment., Patients and Methods: From March 1999 to June 2016, we treated 24 adult patients with primary STS of the thigh's adductor compartment., Results: The mean age at diagnosis was 60 years. There were 13 men and 11 women. The mean follow-up period after the date of the initial treatment was 84 months. The mean tumor size at diagnosis was 13.6 cm. The disease-specific survival was 75.3% at 5 years. Local recurrence was detected in seven patients. The 5-year local recurrence-free rate was 69.9%. The patients with proximal STS had significantly poorer local control, compared to the remaining patients. Twelve (50%) patients developed 14 surgical wound complications. Complications included wound dehiscence ( n = 7), infections ( n = 6), lymphorrhea ( n = 1), wound dehiscence and infection ( n = 1), and infection and lymphorrhea ( n = 1). Six patients underwent additional surgical treatment. Intraoperative blood loss and operative time were related to the incidence of wound complications. Intraoperative blood loss and operative time in patients with proximal adductor STS were significantly larger than those in the remaining patients., Conclusion: We should take care of patients with STS of the thigh's adductor compartment, especially for proximal adductor STS, because they have a greater risk of local recurrence and wound complications.

Background/aim: This study aimed to analyze the decision-making process of treatment and the clinical outcomes of patients with STS aged 75 years and older., Patients and Methods: Overall, 72 patients were reviewed. The mean and median ages were 82 and 81 years, respectively., Results: Of the 72 patients, 17 did not undergo surgical resection. Age was related to the decision to pursue surgical treatment. Resection was performed in 55 patients. The 5-year overall survival was 51.8%. Patients with an American Society of Anesthesiologists physical status (ASA-PS) score of 3 had a worse survival. Twenty-five patients developed metastasis. The median survival time after metastasis in 12 patients who received metastasectomy and/or lung radiofrequency ablation was superior (18.2 months) to that of the remaining 13 patients without any treatment (3.2 months)., Conclusion: Surgical treatment should be considered in elderly patients if their physical condition is not poor. ASA-PS score may be a tool to indicate physical condition., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Thrombomodulin (TM) has multiple biological functions and modulates not only anti-coagulation, but also cell proliferation, adhesion, and anti-inflammation activities. The main function of TM is to activate the anticoagulant pathway of protein C. Soluble TM is related to metastasis by its inactivation of thrombin., Objectives: To clarify the correlation between serum TM levels and clinicopathological parameters., Methods: The plasma TM levels (FU/ml) of 135 primary soft tissue tumors (benign, 67; soft tissue sarcoma (STS), 68) were measured before biopsy or treatment. TM levels were analyzed and compared to various clinicopathological parameters. Log-rank test and Cox proportional analysis were used to evaluate recurrence-free survival, metastasis-free survival, and overall survival., Results: STS tumors had significantly higher TM values (15.9) than benign tumors (13.7) (p= 0.0138). 5-year MFS was 81.1% in low TM and 40.0% in high TM (p= 0.00671), and 5-year OS was 85.5% in low and 52.5% in high TM in grades 1-3 (p= 0.0673). In multivariate COX proportional analysis, high-TM showed a significant difference (MFS: HR 4.37, p= 0.0147; OS: HR 3.60, p= 0.0557) in grades 1-3., Conclusions: We demonstrated that a high level of soluble TM has the potential to be a significant predictor of metastasis and poor prognosis in STS patients. TM is a candidate molecular marker for high metastatic potential and can be clinically useful for guiding therapeutic strategy.

Background: We investigated the long-term clinical efficacy of acridine orange (AO) therapy on the inhibition of local recurrence after marginal or intra-lesional tumor resection in high-grade soft tissue sarcomas (STSs)., Methods: Our study consisted of 48 patients with STSs who received AO therapy after marginal or intra-lesional resection. The median and mean follow-up durations were 76 and 78 months, respectively. Our AO therapy procedure was combined with photodynamic surgery, photodynamic therapy, and radiodynamic therapy., Results: There were 25 men and 23 women, with a mean age of 46 years. The average tumor size at surgery was 8.5 cm. At the last follow-up, 11 patients developed local recurrence. The 5- and 10-year local recurrence-free rates were 78.9% and 73.3%, respectively. In multivariate analysis, tumor size remained significant for local control. None of the patients developed systemic or local complications. All patients recovered activities of daily life before AO therapy., Conclusion: AO therapy can be performed in safety and may be a useful therapy for acquiring long-term local control in patients with high-grade STSs. Tumor size is an important factor for the indication of AO therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background/aim: In patients with soft tissue sarcoma (STS), distinguishing small metastatic pulmonary nodules from benign ones remains difficult. This study aimed to determine the accuracy of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in detecting pulmonary metastasis and identify factors affecting sensitivity with STS., Materials and Methods: The clinical records and chest CT and FDG-PET/CT scans of 102 patients with STS were reviewed to determine the presence of pulmonary nodules., Results: A significant relationship was observed between nodule size and maximum standardized uptake value (SUV max ). For nodules smaller than 5 mm, only 10 out of 76 metastatic pulmonary nodules exhibited FDG accumulation, showing a weak correlation between nodule size and SUV max Conclusion: The role of FDG-PET/CT in differentiating metastatic from benign pulmonary nodules was unsatisfactory, especially for small nodules. Careful follow-up using CT scan may still be appropriate for diagnosing pulmonary nodules smaller than 5 mm., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The aim of this study was to elucidate the clinical outcomes of patients with STSs who received additional excisions after unplanned excisions (UE) using data from the Bone and Soft Tissue Tumor Registry in Japan., Methods: We examined 197 patients with STSs who received an additional excision after a UE. Data from 2006 to 2013 were obtained from the BSTT Registry. There were 112 men and 85 women, with a mean age of 54 years. The mean primary tumor size was 4.7 cm. Tumor depth was classified as superficial (n = 132) or deep (n = 65)., Results: Residual tumor cells were observed in 115 of 197 (58%) specimens at additional excision. Wide margins were achieved in 190 patients, whereas marginal or intra-lesional margins were made in seven patients. One hundred and five patients (53%) required plastic reconstructions. The 5-year disease-specific survival rate was 97.4%. Local recurrence occurred in 15 patients, and the 5-year local recurrence-free rate was 91%. Residual tumor tissue in re-excision specimens was an independent prognostic factor for local control (P = 0.04). The 5-year local recurrence-free rate was significantly worse in patients with residual tumors than in those without residual tumors., Conclusions: We suggest that UEs should be avoided because they require additional excisions and, in many cases, subsequent soft tissue reconstruction. Additional excisions that are sufficiently extensive may improve local control, although patients with residual tumor tissue in re-excision specimens should be carefully followed up., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

The presence of systemic inflammation has been reported to be associated with poor prognosis in patients with soft tissue sarcoma (STS). The cytokine interleukin-6 (IL-6) has pleiotropic effects on various cell types in the tumor microenvironment. The aim of the present study was to determine whether serum IL-6 levels could be useful to assume the differentiation of benign soft tissue tumors from STS and to investigate the possible value of IL-6 for survival and oncological events in patients with STS. The medical records of 99 patients who underwent surgical resection were retrospectively reviewed. Serum IL-6 levels (median: 9.04 pg/ml) in patients with STS were statistically higher than those (3.31 pg/ml) in patients with benign soft tissue tumors. Our analyses confirmed that tumor size and IL-6 level were significant predictors of STS diagnosis. Next, we examined the relationship between IL-6 levels and survival in the 59 patients with STS. C-reactive protein levels, hemoglobin levels, and tumor grade were strongly correlated with IL-6 levels. Tumor grade and IL-6 level remained significant factors for survival and event-free survival. We suggest that measurement of IL-6 levels may be a useful method for identifying patients who are at a high risk of STS and tumor-related death.

Objective: The aim of this study was to determine whether the tumor infiltrative growth pattern on magnetic resonance imaging (MRI) was associated with blood inflammatory markers (C-reactive protein; CRP and Neutrophil-lymphocyte ratio; NLR) and survival in patients with high-grade soft-tissue sarcoma (STS)., Methods: The cohort for this retrospective study included 81 patients with a mean age of 63 years. The tumor depth was superficial or deep in 15 and 66 patients, respectively. The mean CRP and NLR were 1.31 mg/dL and 2.81, respectively. The assessment of a peripheral growth pattern which divided into three patterns on MRI was based on the largest midsection of the tumor., Results: On MRI scans, diffuse-type, focal-type, and pushing-type growth patterns were observed in 18, 33, and 30 patients, respectively. Superficial high-grade STS were prone to show a focal-type pattern on MRI. There were no correlations between growth pattern type and clinicopathological factors such as age, sex, tumor size, and histological grade. However, the incidence of infiltrative growth was significantly higher in patients with elevated CRP (p = 0.0002). In multivariate analysis, growth pattern and CRP were independent prognostic factors for disease-specific survival, metastasis-free survival. Growth pattern was also related to local tumor control., Conclusions: There were significant associations between the tumor growth pattern and CRP levels in patients with high-grade soft-tissue sarcoma. An infiltrative growth pattern and elevated CRP may be associated with inferior disease-specific and metastasis-free survival rates in these patients. Therefore, careful post-treatment follow-up should be conducted in such patients.

Background/aim: We aimed to confirm predictors of survival in soft-tissue sarcoma (STS) patients with metastatic disease at initial presentation in 9 Institutions under the Tokai Musculoskeletal Oncology Consortium., Patients and Methods: Between 2008 and 2013, 47 STS patients with metastatic disease at initial presentation were referred for treatment. The mean follow-up duration was 24 months., Results: The mean C-reactive protein (CRP) levels were 2.47 mg/dl. The mean hemoglobin and albumin levels were 13.1 g/dl and 4.1 g/dl, respectively. Hemoglobin and albumin levels were significantly correlated with CRP levels. In the multivariate analysis, age, CRP levels, and albumin levels were confirmed as independent prognostic factors for disease-specific survival (DSS)., Conclusion: We suggest that the measurements of CRP and albumin levels are a useful method of identifying STS patients with metastasis at initial presentation that have poor prognosis., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Nowadays, small pulmonary nodules are easily detectable in patients with soft tissue sarcomas (STSs) because of highly improved computed tomography (CT) technologies. The purpose of this study was to determine the frequency and significance of the pulmonary nodules detected by CT in high-grade STS patients. 124 patients with high-grade STS were retrospectively reviewed. There were 72 males (57%) and 52 females (43%). Patients' average age was 61 years (median (quartiles) 66 years (48-75), range 8-94 years). Pulmonary nodules were detected in 49 (39.5%) of 124 patients by CT scanning at first presentation. Of 49 patients with nodules at first presentation, 34 (69.4%) had benign lesions, and 13 (26.5%) had metastatic nodules. One patient (2%) had primary lung cancer and the remaining one with one nodule could not be definitively diagnosed due to a short follow-up time. 30 patients (24.1%) of 124 patients developed pulmonary nodules during their clinical progression. Seven (23.3%) had benign lesions, whereas 21 (70%) had metastatic lesions. Primary lung cancer was detected in two patients (6.7%). The size and timing of detection of a pulmonary nodule significantly affected the final clinical diagnosisby multivariate analysis. We conclude that pulmonary nodules can be detected highly frequently in patients with high-grade STSs because of improved CT technologies. Careful follow-up is needed if nodules are detected after initial treatment or during the clinical course of the disease., Competing Interests: The authors have declared that no competing interests exist.

Background: When a soft tissue sarcoma (STS) is located at the distal part of an extremity and involves the tendon, a wide excision usually causes severe functional disability. We therefore developed a minimally invasive surgical technique using intraoperative electron-beam radiotherapy (IOERT) to reduce the incidence of post-operative functional disability in patients with peri-/intra-tendinous STS. We assessed the clinical outcomes of the novel minimally invasive surgery., Methods: The study population included five patients who received treatment for distal extremity STSs. After elevating the tumor mass, including the tendon and nerve from the tumor bed with a wide margin, a lead board was inserted beneath the tumor mass to shield the normal tissue. IOERT (25-50 Gy) was then applied, and the tumor excised with care taken to maintain the continuity of the tendon., Results: In a desmoid patient, local recurrence was observed outside the irradiated field. No cases of neuropathy or bone necrosis were observed. The mean limb function score was excellent in all patients. None of the high-grade sarcoma patients had local recurrence or distant metastasis., Conclusions: Although the current study is only a pilot study with a small number of patients, it shows that this minimally invasive procedure has the potential to become a standard treatment option for selected patients., Trial Registration: H17-250 (registered 2 November 2005) and H25-250 (modified from H17-250, registered 5 December 2013).

Background: Because the efficacy and safety of pazopanib in Japanese patients with soft tissue sarcoma (STS) had not been evaluated previously in a large-scale cohort, the authors investigated the efficacy and safety of pazopanib in 156 Japanese patients with relapsed STS. This was a retrospective study based on the collection of real-life, postmarketing surveillance data., Methods: Patients received pazopanib with the objective of treating local recurrence (n = 20), metastasis (n = 104), and both (n = 32). The patient median age was 53.8 years. The primary objective of this study was to clarify the efficacy of pazopanib for patients with STS., Results: The median treatment duration was 28.7 weeks, and the average dose intensity of pazopanib was 609 mg. Adverse events occurred in 127 patients (81.4%). In addition to the main common toxicities, such as hypertension and liver disorder, pneumothorax (n = 11) and thrombocytopenia (n = 16) also were observed. The median progression-free survival for all patients was 15.4 weeks. The median progression-free survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 18.6 weeks, 16.4 weeks, 15.3 weeks, and 8 weeks, respectively. The median survival for all patients was 11.2 months. The median survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 20.1 months, 10.6 months, 9.5 months, and 7.3 months, respectively., Conclusions: There were apparent differences in the efficacy of pazopanib treatment among histologic types of STS. Pazopanib treatment is a new treatment option; however, adverse events like pneumothorax and thrombocytopenia, which did not occur frequently in the PALETTE study (pazopanib for metastatic soft-tissue sarcoma), should be taken into consideration. Cancer 2016;122:1408-16. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society., (© 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Background: Fibrinogen, a 340 kDa glycoprotein synthesized in the liver, is known to be involved in tumor angiogenesis, enlargement, and metastasis. Elevated plasma fibrinogen levels are associated with tumor progression in many cancer patients. However, there are no reports about differences in fibrinogen levels between benign and malignant soft tissue tumors., Objectives: The purpose of this study was to clarify whether preoperative plasma fibrinogen levels can be used for differential diagnosis of benign or malignant soft tissue tumors., Methods: The plasma fibrinogen levels from 102 primary soft tissue tumor patients were measured before biopsy or treatment. Fibrinogen levels were analyzed and compared to various clinical parameters., Results: According to receiver operating characteristic (ROC) curve analysis, a threshold of serum fibrinogen of 315 mg/dL identified malignant patients with 60.9% sensitivity and 87.5% specificity. The diagnostic accuracy was evaluated by area under the curve (AUC: 0.805). Over 315 mg/dL of fibrinogen was associated with a significantly increased risk of malignancy by multiple logistic regression analysis (OR: 6.452, p= 0.0004)., Conclusions: We demonstrated that plasma fibrinogen levels have a relationship with tumor malignancy of soft tissue tumors. High fibrinogen levels can be a helpful subsidiary tool for the prediction of malignant soft tissue tumors with other diagnostic tools.

Although elevated preoperative serum C-reactive protein (CRP) level is an indicator of a poorer prognosis in many cancers including non-metastatic bone and soft tissue sarcoma, there have been no reports focused on sarcoma patients with advanced stage who had distant metastases. The aim of this study is to determine whether the serum CRP level after metastasis is associated with post-metastatic survival in patients with bone and soft tissue sarcoma. A total of 71 patients were studied including 38 male and 33 female. Of all patients, 22 patients had metastases at presentation. The remaining 49 patients developed initial metastasis after the treatment of primary tumor. The average age at the diagnosis of metastasis was 55 years. Blood was obtained after initial detection of metastasis. CRP levels ranged from 0.1 to 165 mg/L with an average of 16.4 mg/L in all patients. Elevated CRP levels (>3 mg/L) were seen in 31 patients (range 3.1-165). The disease-specific survival after metastasis estimates at 3 and 5 years was 17.1 and 17.1 % for those with an elevated CRP vs. 59.5 and 45.3 % for those with a normal CRP (p < 0.0001). In 49 patients who developed lung metastasis after initial primary treatment, patients with elevated CRP levels also had a poorer post-metastatic survival than patients with normal CRP levels (p < 0.0001). In conclusion, we recommend routine measurement of CRP level to identify the patients who have high risk of death after metastasis.

Aims: The aim of this study was to evaluate the safety and clinical utility of radiofrequency ablation (RFA) retrospectively in non-surgical candidates with recurrent bone and soft-tissue sarcomas., Methods: Percutaneous RFA was used in 52 patients (21 female, 31 male; mean age, 52.2 ± 21.1 years; range 10-87 years) with recurrent bone and soft-tissue sarcomas. The number of tumors was 3 or fewer in 23 patients (44.2 %) and 4 or more in the others, with a mean maximum tumor diameter of 3.0 ± 3.7 cm (range 0.5-18 cm). Safety, tumor control, and prognosis were evaluated., Results: All tumors were ablated after RFA in 21 patients (40.4 %, 21/52), although 14 experienced re-recurrence. Tumors were controlled in 8 cases of recurrence by repeat RFA (n = 7) and surgical intervention (n = 1). Therefore, 15 patients (28.8 %, 15/52) were tumor-free at the end of follow-up (mean follow-up 25.5 ± 24.2 months; range 3.9-117 months). Residual tumors were found after RFA in the other 31 patients (59.6 %, 31/52). Overall survival rates were 73.4 % (95 % CI 61.0-85.9 %) at 1 year, 39.3 % (95 % CI 23.6-54.9 %) at 3 years, and 34.3 % (95 % CI 18.0-50.7 %) at 5 years in all patients. Recurrence-free interval (p = 0.040), tumor number (p = 0.0094), and complete tumor ablation (p < 0.0001) were detected as significant prognostic factors in univariate analysis. The latter two factors were significant in multivariate analysis. The rate of major complications was 0.9 %., Conclusions: RFA is a safe and useful therapeutic option for treatment of recurrent bone and soft-tissue sarcomas. Prognostic factors found in this study will help to identify those patients who would benefit from RFA.

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 aim of this study was to determine whether the combined use of the C-reactive protein (CRP) level and neutrophil-lymphocyte ratio (NLR) before treatment predicts disease-specific survival in adult patients with soft tissue sarcoma (STS)., Methods: We retrospectively reviewed 142 patients who presented with STS between 1995 and 2010., Results: The NLR varied from 0.54 to 7.59. An elevated CRP level was observed in 36 patients before treatment. The patients with both an elevated CRP level and high NLR had a poorer disease-specific survival (46% at 5 years) than the patients with both a normal CRP level and low NLR (87% at 5 years) (P = 0.0005). The patients with both an elevated CRP level and high NLR also had a poorer disease-specific survival than the patients with either an elevated CRP level or high NLR (75.6% at five years) (P = 0.03). There were no significantly prognostic differences between the patients with a normal CRP level and low NLR and those with either an elevated CRP level or high NLR (P = 0.18). A multivariate analysis also showed the preoperative NLR and CRP level to be independent predictors of survival., Conclusions: We recommend the routine measurement of these markers to identify patients with a greater risk of death., (© 2013 Wiley Periodicals, Inc.)

Introduction: Anaemia is present in more than 30 % of patients with various cancers at the time of initial presentation. Anaemia or a lower level of haemoglobin (Hb) is an indicator of poorer prognosis in many cancers. Several studies have also demonstrated that high levels of proinflammatory cytokines contribute to the development of anaemia. However, no studies have assessed the correlation between anaemia and survival in patients with soft tissue sarcoma. The aim of this study was to elucidate the relationship between anaemia and clinical outcome and to determine whether pretreatment anaemia predicted disease-specific survival in patients with adult soft tissue sarcoma., Methods: A total of 376 patients between 2003 and 2010 were retrospectively reviewed. Patients who presented with metastases or/and local recurrence at diagnosis were excluded from this study., Results: Hb levels varied from 8.0 to 17.3 g/dl in all patients. Pretreatment anaemia was seen in 114 patients. Hb levels were significantly correlated to C-reactive protein levels (Spearman ρ = -0.54, p < 0.0001). The tumour histological grade, age and tumour size were also significantly correlated to Hb levels. Patients with anaemia had a worse disease-specific survival (52.6 % at 5 years) than those without anaemia (79.7 % at 5 years) (p < 0.0001). Patients with anaemia also had a worse event-free rate (44 % at 5 years) than those without anaemia (66.3 % at 5 years) (p < 0.0001). Multivariate analysis showed that anaemia remained an independent predictor of survival (p = 0.002) and events (p = 0.0003)., Conclusion: Pretreatment anaemia may be indicative of an aggressive characteristic in patients with soft tissue sarcoma. We recommend the routine measurement of Hb level to identify patients who are at greater risk of death or an event.

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.

Background: Wide-margin resections are an accepted method for treating soft tissue sarcoma. However, a wide-margin resection sometimes impairs function because of the lack of normal tissue. To preserve the normal tissue surrounding a tumor, we developed a less radical (ie, without a wide margin) surgical procedure using adjunctive photodynamic therapy and acridine orange for treating soft tissue sarcoma. However, whether this less radical surgical approach increases or decreases survival or whether it increases the risk of local recurrence remains uncertain., Questions/purposes: We determined the survival, local recurrence, and limb function outcomes in patients treated with a less radical approach and adjunctive acridine orange therapy compared with those who underwent a conventional wide-margin resection., Methods: We treated 170 patients with high-grade soft tissue sarcoma between 1999 and 2009. Fifty-one of these patients underwent acridine orange therapy. The remaining 119 patients underwent a conventional wide-margin resection for limb salvage surgery. We recorded the survival, local recurrence, and functional score (International Society of Limb Salvage [ISOLS]) score) for all the patients., Results: The 10-year overall survival rates in the acridine orange therapy group and the conventional surgery group were 68% and 63%, respectively. The 10-year local recurrence rate was 29% for each group. The 5-year local recurrence rates for Stages II, III, and IV were 8%, 36%, and 40%, respectively, for the acridine orange group and 13%, 27%, and 33%, respectively, for the conventional surgery group. The average ISOLS score was 93% for the acridine orange group and 83% for the conventional therapy group., Conclusion: Acridine orange therapy has the potential to preserve limb function without increasing the rate of local recurrence. This therapy may be useful for eliminating tumor cells with minimal damage to the normal tissue in patients with soft tissue sarcoma., Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of the levels of evidence.

Background: The aim of this study was to determine whether C-reactive protein (CRP) levels or patient's comorbidity before treatment predicted the overall disease-specific survival and local tumour control in high grade soft tissue sarcoma patients., Methods: A total of 332 primary adult soft tissue sarcoma patients were retrospectively reviewed. CRP levels were obtained prior to treatment for all patients. The Charlson comorbidity index (CCI) was used for evaluation as a measure of comorbidity. Patients that presented with metastases at diagnosis were excluded from this study., Results: Elevated CRP levels were seen in 152 patients. CCI score varied from 0 to 4. Two-hundred and sixty-five patients had a score of 0 (no identified comorbidity), and 67 patients had a score of 1 or more. Patients with elevated CRP levels prior to initial treatment had a poorer disease-specific survival (42% at 5 years) than patients with normal CRP levels (82% at 5 years) (p<0.0001). Patients with elevated CRP levels had a poorer local recurrence-free rate after initial treatment (75% at 5 years) than patients with normal CRP levels (89% at 5 years) (p=0.0004). Multivariate analysis also showed the preoperative CRP level to be an independent predictor of survival and local control. Although age in patients with identified comorbidity was significantly higher than those in patients with no-identified comorbidity, CCI was not a predictive factor for either survival or local control., Conclusion: Pretreatment elevated CRP levels were found to be a poor prognostic factor for disease-specific survival and local control for soft tissue sarcoma patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

Background: The aim of this study was to determine whether circulating C-reactive protein (CRP) levels before treatment predict the overall survival and disease-free survival in soft tissue sarcoma patients., Methods: A total of 102 primary soft tissue sarcoma patients from 2003 to 2009 were retrospectively reviewed. The CRP levels were obtained before treatment for all patients. The patients who presented with metastases at diagnosis were excluded from this study., Results: Elevated CRP levels were seen in 18 patients. The tumor histological grade and American Joint Committee on Cancer stage in the patients with elevated CRP levels were significantly higher than those in patients with normal CRP levels. Patients with elevated CRP levels before initial treatment had a poorer overall survival than patients with normal CRP levels (P = .01). The overall survival estimates at 3 and 5 years were 75.3% and 53.8%, respectively, versus 90.3% and 81.3%, respectively. Patients with elevated CRP levels before initial treatment had poorer event-free survival after initial treatment than patients with normal CRP levels (P < .001). The event-free survival estimates at 2 and 5 years were 53.2% and 33.2%, respectively, versus 83.2% and 81.3%, respectively. A multivariate analysis also showed the preoperative CRP level to be an independent predictor of events., Conclusions: The pretreatment serum CRP level may be a marker of aggressive tumor characteristics. Pretreatment elevated CRP levels were found to be a poor prognostic factor for overall survival in a univariate analysis, and for disease-free survival in a multivariate analysis, for soft tissue sarcoma patients., (Copyright © 2011 American Cancer Society.)

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.

The volume doubling time (VDT) is an accurate and reproducible method for the quantitation of the rate and pattern of tumor growth in individual patients. The purpose of this study is to investigate the tumor VDT using chest CT in individual sarcoma patients with lung metastasis and to determine whether VDT is associated with survival after lung metastasis in bone and soft tissue sarcomas. Forty patients had measurable lung metastases in at least two sequential chest CT images taken at least 14 days apart. The VDT was calculated using the method originally described by Schwartz. The median and mean VDT in all 40 patients was 21.5 and 53 days, respectively. Similarly, the median and average VDT in 29 soft tissue sarcoma patients was 26 and 57 days, respectively. The median and mean VDT in 11 bone sarcoma patients was 13 and 42 days, respectively. The current univariate analysis revealed significantly poorer predictive values for VDT in all 40 sarcoma patients and 29 soft tissue sarcoma patients. A multivariate analysis showed the VDT to be an independent predictor of survival in 29 soft tissue sarcoma patients. These results suggest that patients with a shorter VDT and consequently a more rapid rate of tumor growth have a significantly lower chance for long term survival especially in soft tissue sarcoma. The patients with lung metastasis that have a longer VDT should therefore be considered for aggressive treatment even if the lesions are multiple and/or bilateral.

Background: There are very few reports regarding the impact of the symptom that caused patients to consult a doctor and the symptom-to-diagnosis delay on survival for soft tissue sarcoma patients. The purpose of this study is to investigate whether symptom-treatment delay are associated with the presence of metastasis at diagnosis, overall survival and distant metastasis-free survival in primary soft tissue sarcomas., Methods: This study retrospectively reviewed the medical records of 100 newly diagnosed patients with primary soft tissue sarcoma referred to our hospital., Results: Eighteen of 100 sarcoma patients had distant metastases at diagnosis. A multivariate logistic regression analysis revealed that tumor size, tumor site, and the interval between the onset of the initial symptom and the first consultation to our hospital were all found to be significant predictors of distant metastases at diagnosis. The patients (n = 48) who were treated within the first 6 months from the onset of the initial symptom showed significantly better cumulative overall survival rate than those (n = 34) who were diagnosed more than 6 months (5-years: 77.0% vs. 59.7%)., Conclusion: These results suggest that a shorter delay may have a beneficial effect on treatment options and outcome, improving survival in some sarcoma patients., (Copyright © 2011 Wiley Periodicals, Inc.)

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.)