Clinical outcomes of patients with epithelioid sarcomas: impact and management of nodal metastasis.

PURPOSE: An epithelioid sarcoma is a rare histological subtype of a soft tissue sarcoma with a high local recurrence rate, which frequently shows lymph node metastasis. However, because of the rarity of this tumor, the impact of nodal metastasis and its appropriate management remain unclear. The present study investigated the clinical outcomes of patients with epithelioid sarcomas, with a focus on lymph node metastasis. METHODS: We retrospectively evaluated the clinical outcomes of 27 patients with epithelioid sarcomas treated between 1985 and 2015. The log-rank test was used to assess the prognostic variables. RESULTS: The overall local recurrence rate was 33%, and the estimated overall 5-year survival rate was 62%. Hand and foot locations were associated with favorable overall survival. During the follow-up period, new nodal metastasis was noted in 14 patients (52%). The incidence of local recurrence was higher in patients with new nodal metastasis than in patients who did not develop nodal metastasis. The development of new nodal metastasis had a tendency to worsen survival; however, this association was not statistically significant. Lymphadenectomy did not affect overall survival. CONCLUSIONS: Peripheral tumor location is associated with a better prognosis. The development of new nodal metastasis tends to be associated with poor prognosis; however, among patients with nodal metastasis, resection of the metastatic lesions has a low impact on survival.

Feasibility and efficacy of gemcitabine and docetaxel combination chemotherapy for bone and soft tissue sarcomas: multi-institutional retrospective analysis of 134 patients.

BACKGROUND: Bone and soft tissue sarcomas (BSTS) are rare malignant tumors. Recently, the combination of gemcitabine and docetaxel (GD) was shown to have activity as second-line setting in BSTS. However, the efficacy as first-line and adjuvant settings and precise profiles of adverse events in Japanese patients are not known yet. In the present study, the feasibility and efficacy of GD in patients with BSTS were investigated. METHODS: Patients with BSTS treated with GD in our institutions were retrospectively analyzed. Information regarding clinical features, adverse events, and outcome was collected and statistically studied. Factors related to survival were analyzed using log-rank test and Cox proportional hazard regression method. RESULTS: A total of 134 patients were analyzed. GD was carried out as adjuvant setting in 9, first-line in 23, second-line in 56, and third-or-greater line in 46 patients. The response rate (RR) for all patients was 9.7%. RR for the patients treated as adjuvant or first-line setting was 18.8%, whereas that as second-or-greater line was 6.9%. The median progression-free survival (PFS) and overall survival (OS) of all patients were 4.8 (95% CI 3.5-6.1) and 16.4 (95% CI 9.8-22.9) months, respectively. Survival tended to be better in the patients treated as first-line than in those treated as second-or-greater line. Multivariate analysis demonstrated that history of prior chemotherapy (p = 0.046) and response to GD (p = 0.009) was significantly associated with PFS and OS, respectively. The leucopenia and neutropenia were the most frequent adverse events, and grade 3 or 4 leucopenia and neutropenia were observed in 69.4 and 72.4% of the patients. Grade 2 or 3 pneumonitis was observed in one (0.7%) and four (3.0%) patients, respectively. All the patients with pneumonitis had experienced prior chemotherapy and/or radiotherapy. CONCLUSIONS: GD used as both first- and second/later line is effective chemotherapy for a proportion of patients with advanced BSTS. Higher response rate and better outcome was achieved in chemotherapy-naïve patients. This regimen is associated with high incidence of severe hematological toxicity, as well as the risk of severe pneumonitis, especially in pre-treated patients. GD is promising for further analysis by phase III study for the patients with BSTS.

Treatment outcomes of Japanese patients with Ewing sarcoma: differences between skeletal and extraskeletal Ewing sarcoma.

OBJECTIVE: The incidence of Ewing sarcoma is lower in non-Caucasian populations, compared with Caucasian populations, for unknown reasons. Most studies from western countries have reported improvement in outcomes following multi-agent chemotherapy, with no difference in outcome between skeletal and extraskeletal Ewing sarcoma. However, there are few studies of Ewing sarcoma in non-Caucasian populations, with especially few comparing outcomes between skeletal and extraskeletal Ewing sarcoma. Thus, the purpose of this study is to determine whether the outcomes and prognostic factors of Ewing sarcoma in the Japanese population are similar to those in Caucasian populations and to determine whether skeletal and extraskeletal Ewing sarcoma have similar outcomes in Japanese patients. METHODS: We retrospectively evaluated the outcomes of 74 Japanese patients with Ewing sarcoma treated between 1981 and 2011 from the Osaka University Orthopaedic Oncology Group. RESULTS: Extraskeletal Ewing sarcoma, tumors in the extremities, localized disease at presentation and diagnosis after 2000 were significantly associated with a favorable outcome. Among patients with localized disease at presentation, a significantly better outcome was observed for those with extraskeletal Ewing sarcoma, those who underwent a VDC/IE based or VAIA chemotherapy protocol, and those who were diagnosed after 2000. In the multivariable analyses, extraskeletal Ewing sarcoma was an independent predictor of increased overall survival among all patients and the subset of patients with localized disease. CONCLUSIONS: The outcome of patients with Ewing sarcoma in Japan has improved in the last decade. The outcomes and prognostic factors are similar for Japanese and Caucasian patients, though in this series of Japanese patients, a better prognosis was observed for patients with extraskeletal rather than skeletal Ewing sarcoma.

Giant cell tumor of the tendon sheath arising from a membrane surrounding the posterior arch of C1: a case report.

BACKGROUND CONTEXT: Giant cell tumor of the tendon sheath (GCTTS) is a common, benign lesion of the synovial membrane that occurs more often in large joints than in digits. Giant cell tumor of the tendon sheath rarely arises in close proximity to the axial skeleton. PURPOSE: The purpose of the study was to report a rare case of GCTTS arising from the membrane surrounding the posterior arch of the atlas (C1). STUDY DESIGN/SETTING: This is a case report. METHODS: The methods involve clinical findings and review of current literature. RESULTS: In this report, we describe a rare case of GCTTS arising from the membrane surrounding the posterior arch of C1, with no apparent continuity with the facet joint. Here we show the radiographic features, with particular emphasis on positron emission tomography-computerized tomography scans, which have not been previously reported. CONCLUSIONS: We experienced an extremely rare case of GCTTS arising from the membrane surrounding the posterior arch of the C1 vertebra. In spite of the rarity of this disease, GCTTS should be considered in the differential diagnosis of the axial skeletal lesion. Awareness of GCTTS is important because its radiographic features may simulate other neoplastic lesions in the spine.

Atypical and malignant granular cell tumors in Japan: a Japanese Musculoskeletal Oncology Group (JMOG) study.

BACKGROUND: Malignant granular cell tumors (MGCTs) are extremely rare neoplasms with only a limited number of studies published to date. The aim of this study is to elucidate the clinicopathological characteristics and prognostic factors of MGCTs. METHODS: This is a multi-institutional retrospective study of MGCTs with a central pathological review. A total of 18 cases were retrieved. Specimens were blindly reviewed by two pathologists based on the diagnostic criteria by Fanburg-Smith et al. Kaplan-Meier survival probabilities were calculated, and risk factors for poor prognosis were evaluated. RESULTS: Three and fifteen cases were diagnosed as atypical GCTs (AGCTs) and mGCTs according to the Fanburg-Smith et al. classification, respectively. Four (one atypical and three malignant) cases had metastasis at the first presentation, including lymph node metastasis. Three out of ten cases treated with wide resection developed local recurrence. Although prolonged static disease periods of ≥1 year were observed in four cases receiving chemotherapy, all cases with local recurrence or metastasis, including two atypical cases, eventually died of disease. The 5- and 10-year overall survival rates for localized MGCTs were 69.2 and 34.6 %, respectively. The presence of necrosis was revealed as a risk factor associated with adverse clinical outcomes. CONCLUSIONS: MGCTs have high rates of recurrence and metastasis including lymph node metastasis. As histologically atypical cases also have metastatic potential, close attention should be paid to AGCTs. The combination of histological evaluation and tumor size may lead to more accurate diagnosis of this rare neoplasm.

New Magnetic Resonance Imaging Features Predictive for Post-Treatment Ambulatory Function: Imaging Analysis of Metastatic Spinal Cord Compression.

STUDY DESIGN: This is a retrospective, single-institute, radiographical study. OBJECTIVE: The study aimed to determine the correlation of magnetic resonance imaging (MRI) findings observed in metastatic spinal cord compression (MSCC) with post-treatment ambulatory status. SUMMARY OF BACKGROUND DATA: Previous studies have reported various predictors of ambulatory outcome in patients with MSCC, but the relationship between the MRI features and post-treatment ambulatory function remains to be elucidated. METHODS: Fifty-six hospitalized patients with MSCC and risk of MSCC were examined using MRI before therapeutic intervention. Circumferential ratio of cord compression (CRCC), clock position of compression, cross-sectional area (CSA), and change in signal intensity of the spinal cord were recorded. Each imaging feature was analyzed statistically regarding unassisted ambulatory status at the time of hospital discharge as the endpoint. RESULTS: CRCC showed a prognostic value for post-treatment ambulatory function. More than half of CRCC predicted poor functional prognosis with statistical significance. However, the site of cord compression expressed by clock position on axial plane showed no relationship with functional prognosis. CSA of the spinal cord was enlarged in 23% of patients at the level of MSCC, which indicated that cord compression could also be formed by a relative relationship between cord swelling and surrounding mass effect. The said patients showed a better functional outcome. High intensity of the spinal cord on T2-weighted sagittal image was not useful because of lack of inter-rater reliability. CONCLUSION: CRCC on axial T2 image can guide clinicians to identify cancer patients at risk of paraplegia because of MSCC. More than half of CRCC entails urgent treatment despite preserved ambulatory function. Furthermore, some cases of MSCC accompany increased cord CSA. The measurement is also a useful guide to balance the risk and benefit of systemic steroid therapy. MRI is the key imaging modality in the risk assessment of MSCC. LEVEL OF EVIDENCE: 4.

Comparison of clinical and functional outcome between surgical treatment and carbon ion radiotherapy for pelvic chondrosarcoma.

BACKGROUND: As there are no reports of studies in patients with pelvic chondrosarcoma treated with carbon ion radiotherapy (CIRT), the aim of this study was to evaluate the applicability of CIRT for patients with chondrosarcoma of the pelvis. METHODS: The medical records of 31 patients with chondrosarcoma of the pelvis treated either by surgical resection or by CIRT between 1983 and 2014 were reviewed. There were 22 males and 9 females with a median age of 43 years (range 16-77 years). The median duration of follow-up was 66 months (range 5-289 months). Twenty-four patients underwent surgery, and 7 patients received CIRT (70.4 GyE in 16 fractions over 4 weeks). RESULTS: The overall local recurrence rate was 32 %, and the estimated overall 5- and 10-year survival rates were 72 and 57 %, respectively. The mean Musculoskeletal Tumor Society functional score was 59 %. The treatment procedures (surgery or CIRT) did not affect overall survival (P = 0.347). However, the patients who underwent surgery had impaired function compared with those who received CIRT (P = 0.03). CONCLUSION: Although more patients need to be monitored to assess the clinical and functional outcomes of CIRT for patients with chondrosarcoma of the pelvis, this treatment might offer an acceptable alternative.

Intraoperative extracorporeal autogenous irradiated tendon grafts for functional limb salvage surgery of soft tissue sarcomas of the wrist and hand.

BACKGROUND: In patients with soft tissue sarcoma of the wrist and hand, limb salvage operation is extremely challenging for surgeons in attempting a complete tumor resection with negative surgical margins. In this study, we report four patients with soft tissue sarcoma of the wrist and hand treated by limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts. METHODS: The patients were all male, and the mean age at the time of surgery was 45 years. Histological diagnoses included clear cell sarcoma in two patients, synovial sarcoma in one, and angiosarcoma in one. All four patients had high grade tumors, wherein three had American Joint Committee on Cancer (AJCC) stage III disease and one with AJCC stage IV disease. The tumors were resected en bloc with involved tendons. The tendons were isolated from the resected tissues, irradiated ex vivo, and re-implanted into the host tendons. In one patient, the bone was resected additionally because of tumor invasion to the bone. Hand function was evaluated using Musculoskeletal Tumor Society (MSTS) rating system. RESULTS: Of the four patients, three died of distant metastatic disease. The remaining patient lives and remains disease-free. The mean follow-up period was 33 months. One patient had local recurrence outside the irradiated graft at 20 months after surgery. The functional rating was 22. Lower scores were seen in patients with reconstruction of flexor tendons than extensor tendons. CONCLUSIONS: Limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts is an acceptable method in selected patients with soft tissue sarcoma of the wrist and hand.

Clinical outcomes for patients with synovial sarcoma of the hand.

PURPOSE: Soft tissue sarcoma of the hand is rare, and one of the most common histological diagnosis is synovial sarcoma. We report the clinical outcomes of patients with synovial sarcoma of the hand and discuss treatment strategies. METHODS: We reviewed five patients with synovial sarcoma of the hand treated at our institutions from 1983 to 2013. The mean patient age at the time of diagnosis was 36.6 years (range, 20-62 years). Two patients underwent marginal excision after neoadjuvant chemotherapy, followed by radiation therapy, one underwent wide local excision and two received chemotherapy and radiation therapy. RESULTS: The average duration of follow-up for all patients was 88.2 months (range, 14-218 months). Two patients continuously remained disease free, two experienced local recurrence requiring additional surgery and then showed no evidence of disease, and one who had distant metastasis at diagnosis died of the disease. No patients developed lymph node metastasis. The estimated 5-year overall survival was 80%. CONCLUSIONS: Our case series suggests that patients with localised synovial sarcoma of the hand may have favourable outcomes. Wide excision or marginal excision, followed by radiation therapy combined with chemotherapy, represent acceptable treatment strategies for synovial sarcoma of the hand. Regional lymph node dissection does not seem to be essential for synovial sarcoma of the hand.

Intercalary endoprosthesis for salvage of failed intraoperative extracorporeal autogeneous irradiated bone grafting (IORBG) reconstruction.

Intraoperative extracorporeal autogeneous irradiated bone grafting (IORBG) after femoral tumor resection ultimately sometimes will fail in patients achieving long-term survival. There are several alternative surgical approaches for revision of these reconstructions. In 2002 and 2005, two patients with femoral intercalary resection of malignant tumor (synovial sarcoma and MFH) underwent IORBG reconstruction with intramedullary nail or plate. At 32 and 96 months after IORBG reconstruction, both patients had failed IORBG (pathological fracture) in the femur. We used custom-made endoprostheses in these two patients to reconstruct femoral diaphyseal bone defect after excision of failed IORBG. Follow-up of the patients averaged 40.5 months (range, 39-42 months) after endoprosthetic revision. Musculoskeletal Tumor Society scores averaged 75% (66-83%). When used to salvage massive IORBG failure from fractures, intercalary endoprosthetic revision preserves limb function with minimal complications.

A new strategy to remove broken femoral mega-prostheses with hollow trephine reamers.

Prosthetic replacement for the reconstruction of bone tumor is the standard method in limb salvage surgery. However, the breakages of prosthesis in these patients are frequent because the patients are young and active. Removal of the broken stem remained in the bone medulla is a highly difficult technical procedure in revision surgery. This article describes a new method to remove the well-fixed broken femoral stem with a hollow trephine reamer in patients with prosthetic replacement of the distal femur for primary bone tumors.

Surgery with vascular reconstruction for soft-tissue sarcomas in the inguinal region: oncologic and functional outcomes.

BACKGROUND: Treatment of soft-tissue sarcomas involving the inguinal region remains challenging because of difficulties in achieving wide surgical margins due to anatomical features. The study aimed to analyze the oncologic and functional outcomes of wide resection with vascular reconstruction for inguinal soft-tissue sarcomas. METHODS: Three men and seven women were treated for inguinal soft-tissue sarcomas by wide surgical resection with vascular reconstruction. RESULTS: Arteries and veins were replaced in nine patients, and artery replacement alone was carried out in one patient. Femoral nerve resections were performed in six patients. One patient and five patients developed local recurrence and distant metastases, respectively. Limb salvage was achieved in 9 of 10 patients (90%). Six patients and one patient developed vascular (arterial graft occlusion [n = 1], lymphedema [n = 5]) and nonvascular (hematoma [n = 1]) complications, respectively. Five-year arterial primary patency was 77%. Five-year disease-free and overall survival rates were 45% and 77%, respectively. Functional outcome scores at latest follow-up averaged 87.5% for Musculoskeletal Tumor Society 1993. CONCLUSIONS: En-bloc resection of major critical structures along with tumor and vascular reconstructions using synthetic grafts is a feasible option in limb salvage surgery for inguinal soft-tissue sarcomas.

Malignant mixed tumor of the soft tissue occurring after total knee arthroplasty.

A 70-year-old woman developed a malignant mixed tumor of the soft tissue 2 years after total knee arthroplasty. A 5×3×3-cm elastic hard tumor at the lateral side of the surgical scar was resected. The tumor showed focal infiltration into surrounding adipose and fibrous tissues, focal necrosis, and vascular infiltration. It was diagnosed as malignant. Mixed tumor, or myoepithelioma, of the soft tissue is a relatively rare tumor that was recently recognized as a disease entity; the vast spectrum of myoepithelial cell differentiation and the resultant morphologic diversity might increase the difficulty of the histological diagnosis. Postoperatively, the patient did not receive adjuvant therapy and no recurrence of the tumor was observed for 6 years. Range of motion of her left knee is -5° extension and 90° flexion; however, her activities of daily living are restricted because of general fatigue, partly due to hepatoma and chemotherapy.Despite the increase of artificial implant use worldwide, reports of peri-implant tumor formation are rare. Although we do not know the exact mechanism of tumor genesis, we consider the fibroblast formation in the routine healing process to be a possible mechanism. Further investigation is necessary to identify coexisting factors that increase the risk of tumor formation after implantation.

Prosthetic reconstruction for tumors of the distal tibia. Report of two cases.

Prosthetic reconstruction in two patients with malignant bone tumors of the distal tibia was conducted. The diagnoses were metastatic bone tumor in one patient and low grade central osteosarcoma in another. The mean duration of follow-up was 5.5 years (3 and 8 years). Reconstruction was achieved using custom-made prosthesis (JMM, Japan Medical Materials), which replaced the distal tibia. In the patient with metastasis, local recurrence occurred 8 months after the primary surgery and the recurrent tumor was resected. Both patients were free from neoplastic disease at the latest follow-up. The average functional scores according to the system of the Musculoskeletal Tumor Society were 25 and 23. Custom-made prostheses allow an early return to functional weight-bearing without major complications. This technique provides a safe and effective method of stabilization for properly selected malignant tumors of the distal tibia.

Eleven cases of cardiac metastases from soft-tissue sarcomas.

OBJECTIVE: Cardiac metastasis is a highly life-threatening condition because it leads to cardiac failure. However, it is difficult to diagnose because its precise clinical features are unknown. Here, we report 11 cases of cardiac metastasis from soft-tissue sarcoma, and discuss its diagnosis and treatment. METHODS: Of 641 patients with soft-tissue sarcoma treated in our institute between 1996 and 2009, we retrospectively reviewed the medical records of 11 patients whose cardiac metastases were diagnosed while they were alive. RESULTS: The most common primary tumor was leiomyosarcoma (n= 5), followed by clear cell sarcoma (n= 2). In all cases, metastases to other organs, including lungs (n= 10), soft tissues (n= 5) and bones (n= 4) were found along with cardiac metastases. Cardiac metastasis was diagnosed by echocardiography in six cases and by computed tomography in four cases. In four patients, cardiac metastasis was not detected by chest computed tomography as follow-up to lung metastases and echocardiography was required to make the diagnosis. Although five patients complained of exertional dyspnea, four were asymptomatic. Seven cases were treated with radiotherapy. No patient had surgery for their cardiac metastasis. The median survival of patients who received radiation therapy was 10.5 months; that of those who did not was 3.5 months. CONCLUSIONS: Cardiac metastasis is often asymptomatic. Echocardiography is better than computed tomography for diagnosing cardiac metastasis, and should be considered in all patients presenting with soft-tissue metastases. Owing to the highly life-threatening nature of cardiac metastases and the possibility of soft-tissue dissemination, treatment with radiation therapy is recommended immediately on diagnosis.

Limb salvage operation using intraoperative extracorporeal autogenous irradiated bone and tendon graft for myxoid liposarcoma on dorsum of foot.

Foot and ankle sarcomas are conventionally treated with amputation. In this article, we report a case of myxoid liposarcoma on the dorsum of the foot treated by limb salvage operation with intraoperative extracorporeal autogenous irradiated bone and tendon grafts. The patient was a 76-year-old woman with a soft tissue tumor beneath the extensor tendons with attachment to the tarsal and metatarsal bones. The histological diagnosis was myxoid liposarcoma. Wide margin was achieved by splitting the tarsal and metatarsal bones into dorsal and plantar parts. The dorsal part of the bones and tendons was isolated from the resected material, irradiated ex-vivo and re-implanted into the host's bones and tendons. No local recurrence was detected around the irradiated bones and tendons during the follow-up at 36 months. The functional rating was 74% according to the ISOLS rating system. This method may be a better procedure for limb salvage operation of sarcomas on the dorsum of the foot.

Synovial sarcoma is a stem cell malignancy.

Synovial sarcoma (SS) is a malignant soft tissue tumor characterized by its unique t(X;18)(p11;q11) chromosomal translocation leading to the formation of the SS18-SSX fusion gene. The resulting fusion protein product is considered to play as an aberrant transcription factor and transform target cells by perturbing their gene expression program. However, the cellular origin of SS is highly debated. We herein established two novel human SS cell lines, named Yamato-SS and Aska-SS, and investigated their biological properties. We found the self-renewal ability of these cells to generate sarcospheres, to form tumors in serial xenotransplantation and reconstitute the tumor phenotypes without fractionation by any surface markers. Both SS cells as well as clinical tissue specimens from 15 patients expressed the marker genes-associated stem cell identity, Oct3/4, Nanog, and Sox2. We also found that both SS cells displayed limited differentiation potentials for mesenchymal lineages into osteocytes and chondrocytes albeit with the expression of early mesenchymal and hematopoietic lineage genes. Upon SS18-SSX silencing with sequence-specific siRNAs, these SS cells exhibited morphological transition from spherical growth in suspension to adherent growth in monolayer, additional expression of later mesenchymal and hematopoietic lineage genes, and broader differentiation potentials into osteocytes, chondrocytes, adipocytes, and macrophages in appropriate differentiation cocktails. Collectively, these data suggest that a human multipotent mesenchymal stem cell can serve as a cell of origin for SS and SS is a stem cell malignancy resulting from dysregulation of self-renewal and differentiation capacities driven by SS18-SSX fusion protein.