Diagnostic Utility of 99m Tc-MDP Bone Scintigraphy for Nivolumab-Induced Inflammatory Arthritis.

ABSTRACT: Immune checkpoint inhibitors can revive exhausted helper T-cells, and inflammatory cell reactivation may cause autoimmune disease-like conditions. Drug-induced arthritis is an immune-related adverse event, but the diagnostic approach is undefined. We present the diagnostic utility of 99m Tc-MDP bone scintigraphy for nivolumab-induced inflammatory arthritis. A 67-year-old man with hypopharyngeal carcinoma presented bilateral multiple metacarpophalangeal joint pain and swelling at each nivolumab administration. Regular imaging findings were atypical for inflammatory arthritis and did not fulfill the criteria for rheumatoid arthritis. We diagnosed nivolumab-induced inflammatory arthritis based on clinical symptoms and the symmetrical moderate uptake of the affected joints on 99m Tc-MDP bone scintigraphy.

Needle tract seeding of a sclerosing epithelioid fibrosarcoma in a biopsy tract: a case report.

BACKGROUND: A sclerosing epithelioid fibrosarcoma (SEF) is an uncommon tumor of the deep soft tissue. An SEF has been described as a low-grade tumor with high local recurrence and metastatic rates. Generally, in bone and soft tissue tumors, a resection of the biopsy route is recommended; however, there is limited evidence with respect to the dissemination of the tumor tissue during a needle biopsy. CASE PRESENTATION: A mass in the right pelvic cavity, with no symptoms, was observed in a 45-year-old woman during a gynecological examination. Computed tomography (CT) revealed a multilocular mass with calcification in the pelvic cavity. The magnetic resonance imaging (MRI) showed an iso-signal intensity on T1 weighted images and hypo- and iso-signal intensity on T2 weighted images. The CT-guided core needle biopsy was performed using a dorsal approach, and the biopsy diagnosis was a low-grade spindle cell tumor. The tumor was excised using an anterior approach. The tumor tissue comprised spindle cells and epithelioid cells with irregular nuclei, and the immunohistological analysis was positive for vimentin and epithelial membrane antigen, which was consistent with a diagnosis of sclerosing epithelioid fibrosarcoma. Five years after the surgery, the MRI showed a tumor recurrence in the subcutaneous tissue of the right buttock, which was consistent with the needle biopsy tract. The patient underwent a tumor excision, and the resected tumor was similar to the primary tumor. CONCLUSIONS: The recurrent tumor was excised with a surgical margin, and the tumor specimen had the histological features of a sclerosing epithelioid fibrosarcoma. It was difficult to investigate the association of the core needle biopsy with the tumor recurrence because the approach of the biopsy tract is usually same as that used in a tumor excision. However, the present case indicated the tumor may recur in the biopsy tract of a soft tissue sarcoma. Surgeons should be aware of the possibility of disseminating tumor tissues in a needle biopsy.

A validation study for the utility of serum microRNA as a diagnostic and prognostic marker in patients with osteosarcoma.

In our previous study, osteosarcoma advanced locally, and metastasis was promoted through the secretion of large number of small extracellular vesicles, followed by suppressing osteoclastogenesis via the upregulation of microRNA (miR)-146a-5p. An additional 12 miRNAs in small extracellular vesicles were also detected ≥6× as frequently in high-grade malignancy with the capacity to metastasize as in those with a low metastatic potential. However, the utility of these 13 miRNAs for determining the prognosis or diagnosis of osteosarcoma has not been validated in the clinical setting. In the present study, the utility of these miRNAs as prognostic and diagnostic markers was therefore assessed. In total, 30 patients with osteosarcoma were retrospectively reviewed, and the survival rate was compared according to the serum miRNA levels in 27 patients treated with chemotherapy and surgery. In addition, to confirm diagnostic competency for osteosarcoma, the serum miRNA levels were compared with those in patients with other bone tumors (n=112) and healthy controls (n=275). The patients with osteosarcoma with high serum levels of several miRNAs (miR-146a-5p, miR-1260a, miR-487b-3p, miR-1260b and miR-4758-3p) exhibited an improved survival rate compared with those with low levels. In particular, patients with high serum levels of miR-1260a exhibited a significantly improved overall survival rate, metastasis-free survival rate and disease-free survival rate compared with those with low levels. Thus, serum miR-1260a may potentially be a prognostic marker for patients with osteosarcoma. Moreover, patients with osteosarcoma had higher serum miR-1261 levels than those with benign or intermediate-grade bone tumors and thus may be a potential therapeutic target, in addition to being useful for differentiating whether or not a bone tumor is high-grade. A larger investigation is required to clarify the actual utility of these miRNAs in the clinical setting.

Joint-preservation surgery for bone sarcoma in adolescents and young adults.

Bone sarcoma often occurs in childhood, as well as in adolescents and young adults (AYAs). AYAs differ from pediatric patients in that their bone is skeletally mature and the physis has almost disappeared with the completion of growth. Although AYAs spend less time outside, they often participate in sports activities, as well as driving, working, and raising a family, which are natural activities in daily living. Multidisciplinary approaches involving imaging, multi-agent chemotherapy, surgical procedures, and careful postoperative care has facilitated an increase in limb-sparing surgery for bone sarcoma. In addition, recent advances in imaging modalities and surgical techniques enables joint-preservation surgery, preserving the adjacent epiphysis, for selected patients following the careful assessment of the tumor margins and precise tumor excision. An advantage of this type of surgery is that it retains the native function of the adjacent joint, which differs from joint-prosthesis replacement, and provides excellent limb function. Various reconstruction procedures are available for joint-preserving surgery, including allograft, vascularized fibula graft, distraction osteogenesis, and tumor-devitalized autografts. However, procedure-related complications may occur, including non-union, infection, fracture, and implant failure, and surgeons should fully understand the advantages and disadvantages of these procedures. The longevity of the normal limb function for natural activities and the curative treatment without debilitation from late toxicities should be considered as a treatment goal for AYA patients. This review discusses the concept of joint-preservation surgery, types of reconstruction procedures associated with joint-preservation surgery, and current treatment outcomes.

A Viability Analysis of Tumor-Bearing Frozen Autograft for the Reconstruction After Resection of Malignant Bone Tumors Using 99m Tc-MDP Scintigraphy.

PURPOSE OF THE REPORT: Several methods are used to reconstruct bony defects after malignant tumor excision. Tumor-bearing frozen autograft reconstruction is a biological procedure in which tumor-bearing bone is reused after devitalization with liquid nitrogen to kill tumor cells. The viability of frozen autografts has not been fully evaluated over time. We therefore aimed to evaluate the viability of devitalized bone grafts, using 99m Tc-MDP scintigraphy. PATIENTS AND METHODS: Seventy-four patients who underwent frozen autograft reconstruction after the excision of a malignant bone tumor were enrolled. Two hundred forty-two postoperative 99m Tc-MDP scans were reviewed. For a quantitative analysis, the region of interest on the frozen bone segment and a symmetric region of interest on the contralateral normal area were manually set. The radioactive tracer uptake ratio was calculated by dividing the count density of the frozen bone segment by that of the contralateral normal area in each image. An uptake ratio of 0.9 to 1.1 was defined as a normalization of tracer uptake. RESULTS: Normalization of tracer uptake was achieved in 95% to 97% of the cases by 60 months postoperatively, and earlier in the middle zone and peripheral zone in the pedicle freezing group in comparison to the free freezing group (both P = 0.03). Fracture and nonunion was associated with a low uptake ratio, whereas infection was associated with a high uptake ratio before the occurrence of the event. CONCLUSIONS: The calculation of the uptake ratio using 99m Tc-MDP scans was an objective and accurate evaluation method. The period to normalization of tracer uptake in the pedicle frozen bone was significantly earlier than that in the free frozen bone. The postoperative complications can be also predicted.

A Traumatic Intermuscular Hematoma Mimicking a Soft-tissue Tumor: A Case Report and Literature Review.

BACKGROUND/AIM: Certain types of soft-tissue tumors are sometimes combined with bleeding, resulting in difficulty distinguishing them from a mere hematoma when patients with unnoticed soft-tissue tumor sustain trauma. CASE REPORT: A 43-year-old man presented with left calf pain after running practice. Magnetic resonance imaging (MRI) revealed that the lesion seemed to be a soft-tissue mass with surrounding edema, located between the soleus and medial gastrocnemius muscle. An unnoticed soft-tissue tumor with traumatic bleeding was suspected. Two weeks later, MRI revealed that the bleeding had decreased, and the mass had changed to hyperintense on T1-weighted MRI, with heterogenic intensity on T2-weighted MRI. The calf pain had nearly almost resolved. CONCLUSION: Changes in MRI findings of traumatic hematoma over time are important for the diagnosis. In particular, changes in the intensity of the mass in the subacute phase from the acute phase must be considered when determining the possibility of traumatic hematoma.

Primary Osteosarcoma in Patients Over 75 Years of Age: A Case Series and Literature Review.

BACKGROUND/AIM: Little is known about the clinical characteristics in older patients of ≥75 years of age with primary osteosarcoma due to its rarity. We aimed to understand the clinical characteristics in these patients in order to make an appropriate diagnosis and provide treatment. PATIENTS AND METHODS: The medical records of eight patients of ≥75 years of age with primary osteosarcoma were retrospectively reviewed. We investigated their clinical features, imaging findings, histopathological findings, treatment methods, and oncological outcomes. RESULTS: There were two male and six female patients, with a mean age of 80 years. The mean follow-up period was 44 months. The initial symptom was pain in five, swelling in two, and a mass in one. The initial diagnosis was osteoarthritis in two, lumbar canal stenosis in two, benign bone tumor in four. The mean period from the first time the patient noticed symptoms to referral was 25 months. Two patients had a history of surgical curettage at their previous hospital for bone tumor that was considered benign. Lung metastasis was observed at presentation in three patients. The mean tumor size was 129 mm in its greatest dimension. Surgical treatment was performed on six patients, including frozen autograft reconstruction in one. Carbon-ion radiotherapy was conducted in one patient due to an unresectable pelvic lesion. CONCLUSION: Diagnosis requires care because the radiological and histological findings of primary osteosarcoma in patients ≥75 years of age are often non-specific, in addition to their delayed consultation. Individualized treatment including surgical procedure and radiotherapy is essential for older patients to maintain a good quality of their lives.

Family cancer history and smoking habit associated with sarcoma in a Japanese population study.

Sarcoma is a rare cancer, and little is known about the etiology, lifestyle epidemiology, and actual circumstances of treatment in hospitals in Japan. Understanding these issues is essential for the effective prevention and treatment of sarcoma. We therefore investigated the incidence of a personal and family cancer history in a total of 1320 sarcoma patients at the National Cancer Center Hospital. In addition, obesity, hypertension, dyslipidemia, diabetes mellitus, drinking, smoking, age and sex were compared in a descriptive study of 1159 of these sarcoma patients who were ≥ 20 years of age, and 7738 controls derived from the National Health and Nutrition Examination Survey in Japan. A total of 8% of sarcoma patients had a personal history of another cancer, and 30% of soft tissue sarcoma patients had a family cancer history in a first-degree relative (malignant peripheral nerve sheath tumor, 52%; leiomyosarcoma, 46%). A smoking habit was associated with the development of sarcoma (odds ratio [OR], 2.05; 95% confidence interval, 1.78-2.37; p < 0.01). According to the histology, the ORs for undifferentiated pleomorphic sarcoma (UPS) of bone, UPS of soft tissue, and liposarcoma were 5.71, 3.04, and 2.92, respectively. A family cancer history may be associated with certain soft tissue sarcomas, and a smoking habit was significantly associated with the development of sarcomas; however, further studies are necessary.

The Therapeutic Effect and Clinical Outcome of Immune Checkpoint Inhibitors on Bone Metastasis in Advanced Non-Small-Cell Lung Cancer.

Introduction: In advanced non-small-cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs) have been reported a better treatment outcome on primary lesions, however, the therapeutic effect on bone metastases has not been clarified. This study investigates the therapeutic effect of ICIs on bone metastases in advanced NSCLC. Methods: The data of patients with advanced NSCLC, treated with ICIs from 2016 to 2019 at our hospital, were analyzed. The therapeutic effects of ICIs on primary lung and metastatic bone lesions, concomitant use of bone modifying agents (BMA), treatment outcomes, and frequency of immune-related adverse events (irAEs) and skeletal-related events (SREs) were investigated. Results: A total of 29 patients were included (19 men and 10 women; mean age, 64.2 years). Among the ICIs, pembrolizumab was the most used (55.2%), and concomitant use of BMA was prevalent in 21 patients (zoledronic acid=1, denosumab=20). The therapeutic effect was partial response (PR) in 10.3% (n=3) on primary lung lesions by RECIST 1.1, complete response (CR) in 6.9% (n=2) and PR in 17.2% (n=5) on bone metastatic lesions by MDA criteria. ICIs suppressed the progression of bone metastasis in 21 cases (72.4%). All patients in CR and PR were treated with pembrolizumab and denosumab. SREs and irAEs were developed in 3.4% (n=1) and 20.7% (n=6), respectively. The median survival time after treatment with ICIs was 11.0 months. Concomitant therapy with ICIs and denosumab significantly prolonged the overall survival compared to ICI-only therapy (16.0 months vs. 2.5 months, p<0.01). Conclusions: This study showed that treatment with ICIs may successfully suppress the progression of bone metastasis in advanced NSCLC. Pembrolizumab with denosumab had the highest therapeutic effect on both primary lung lesions and bone metastases. Systemic treatment with this combination and conservative treatment of bone metastasis could be one of the options in the treatment of advanced NSCLC.

Primary total knee arthroplasty assisted by computed tomography-free navigation for secondary knee osteoarthritis following massive calcium phosphate cement packing for distal femoral giant-cell bone tumor treatment: a case report.

BACKGROUND: Giant cell tumor of bone (GCTB) is an intermediate tumor commonly arising from the epiphysis of the distal femur and proximal tibia. Standard GCTB treatment is joint-preserving surgery performed using thorough curettage and the filling of the cavity with allo-, auto-, polymethyl methacrylate (PMMA), or synthetic bone graft. Calcium phosphate cement (CPC) is an artificial bone substitute, which has the benefit of being able to adjust defects, consequently inducing immediate mechanical strength, and promoting biological healing. Secondary osteoarthritis may occur following GCTB treatment and may need additional surgery if severe. However, details regarding surgery for secondary osteoarthritis have not been fully elucidated. There are no reports on the use of total knee arthroplasty (TKA) for the treatment of secondary osteoarthritis following CPC packing. The insertion of an alignment rod is a standard procedure in TKA; however, it was difficult to perform in this case due to CPC. Therefore, we used a computed tomography (CT)-free navigation system to assist the distal femur cut. This study presents a knee joint secondary osteoarthritis case following CPC packing for GCTB curettage that was treated with standard TKA. CASE PRESENTATION: A 67-year-old Japanese woman, who was previously diagnosed with left distal femur GCTB and was treated by curettage and CPC packing 7 years ago, complained of severe knee pain. Left knee joint plain radiography revealed Kellgren and Lawrence (K-L) grade 4 osteoarthritis without evidence of tumor recurrence. Therefore, she was scheduled for TKA. There are no reports on the cutting of a femoral condyle surface with massive CPC with accurate alignment. Because it is difficult to insert the alignment rod intramedullary and cut the femoral condyle with CPC, we planned CT-free navigation-guided surgery for accurate bone cutting using an oscillating tip saw system to prevent CPC cracks. We performed standard TKA without complications, as planned. Postoperative X-ray showed normal alignment. Knee Society Knee Score (KSKS) and Knee Society Function Score (KSFS) ameliorated from 27 and 29 to 64 and 68, respectively The patient can walk without a cane postoperatively. CONCLUSION: There was no report about the surface TKA guided by CT-free navigation after primary GCT surgery with CPC. We believe that this case report will help in planning salvage surgery for secondary osteoarthritis after CPC packing.

Management of Soft-tissue Tumors With a Size of 2-5 cm, Including Malignancy.

BACKGROUND/AIM: The management of soft-tissue tumors of 2-5 cm is not specified. We investigated the management of these cases. PATIENTS AND METHODS: Among 105 cases with soft-tissue tumors from 2014 to 2021, 38 with tumors of 2-5 cm were retrospectively reviewed. The clinical characteristics, diagnosis, and management were investigated. RESULTS: The study population included 14 males and 24 females (mean age=57 years). Common histological diagnoses included lipoma, epidermal cyst, and hemangioma as benign tumors, and leiomyosarcoma (n=2) and metastatic soft-tissue carcinoma (n=1) as malignant tumors. Magnetic resonance imaging, needle and excisional biopsy were performed in 35, 19 and 19 cases, respectively. The mean follow-up period was 7 months. No recurrence was observed. CONCLUSION: Malignancy exists, even in soft-tissue tumors of 2-5 cm (3/38; 8%). To avoid unplanned excision, needle biopsy should be considered for cases with magnetic resonance imaging abnormalities.

A scoring system combining clinical, radiological, and histopathological examinations for differential diagnosis between lipoma and atypical lipomatous tumor/well-differentiated liposarcoma.

This study evaluated the diagnostic accuracy of clinical, radiological, and histopathological examinations for differential diagnosis between atypical lipomatous tumor (ALT)/well-differentiated liposarcoma (WDLS) and lipoma, and aimed to develop a new combined scoring system for the preoperative diagnosis of ALT/WDLS. Eighty-nine lipomas and 56 ALT/WDLS were included and their clinical characteristics, magnetic resonance imaging (MRI) findings, histological findings by hematoxylin and eosin (HE) staining were investigated. Then, univariate and multivariate logistic regression analyses were performed for the findings, and a combined scoring system consisted of predictive factors of ALT/WDLS was developed. The univariate and multivariate logistic regression analyses revealed that tumor location (lower extremity), deep site, size (> 11 cm), thick septa (> 2 mm), enhancement of septa or nodular lesions, and lipoblasts were significantly different for the diagnosis of ALT/WDLS. We developed a combined scoring system based on the six predictive factors (total 0-16 points, the cutoff was 9 points). The area under the curve was 0.945, and sensitivity was 87.6% and specificity was 91.1% by the receiver operating characteristics curve. This combined scoring system does not require special equipment and reagents such as fluorescence in situ hybridization (FISH), and anyone can use it easily in many medical institutions with high diagnostic accuracy.

Pretreatment Neutrophil Count and Platelet-lymphocyte Ratio as Predictors of Metastasis in Patients With Osteosarcoma.

BACKGROUND/AIM: Systemic inflammation responses have been associated with cancer development, progression and metastasis. Little is known about the risk of metastasis based on inflammatory-based scores in patients with osteosarcoma. PATIENTS AND METHODS: A total of 65 osteosarcoma patients without metastasis at presentation were enrolled in this retrospective study. All had been diagnosed histologically, and their laboratory data at the first visit were collected from medical records. The inflammation-based scores, tumor size, location, staging, pathological fracture, treatment methods, follow-up periods, and metastasis-free duration were evaluated. RESULTS: A multivariate Cox regression analysis revealed that a high platelet-lymphocyte ratio (PLR) >116 [hazard ratio (HR)=3.8, 95% confidence interval =1.5-9.3; p<0.01], and neutrophil count (NC) ≤4,030/µl (HR=4.5, 95%CI=1.7-12.3; p<0.01), were independent risk factors significantly associated with metastasis of osteosarcoma patients. CONCLUSION: The combination of a high PLR >116 and NC ≤4,030/µl before treatment was a useful inflammatory-based prognostic indicator for metastasis in patients with osteosarcoma.

Impact of Tumor Growth Speed of Primary Lesions on the Clinical Outcomes of Appendicular Skeletal Metastases.

BACKGROUND/AIM: This study aimed to investigate the clinical influence of the growth speed of primary lesions on appendicular skeletal metastases to provide an optimal treatment strategy for the metastases. PATIENTS AND METHODS: Fifty-seven patients who underwent surgery for appendicular skeletal metastases between 2008 and 2020 were included. According to the growth speed of primary lesions, the patients were divided into the S group (slow-to-moderate, n=34) and the R group (rapid, n=23), and the outcomes were investigated. RESULTS: The period from diagnosis of skeletal metastases to pathological fracture (PF) was shorter in the R group than in the S group (p=0.24). The overall survival of the S group was significantly better than that of the R group (p=0.02). CONCLUSION: The appendicular skeletal metastases of the primary tumor with rapid growth speed have a high risk of PFs developed early from the diagnosis of skeletal metastases, and the prognosis may be poor.

Clinical characteristics of patients with undergoing unplanned excisions of malignant soft tissue tumors.

INTRODUCTION: Malignant soft tissue tumors are rare tumors representing <1% of all malignancies. As these tumors are rare, it is not uncommon that malignant soft tissue tumor excision is performed without the required preoperative imaging, staging, or wide resection margins for sarcomas. The purpose of this study was to investigate the characteristics of patients with undergoing unplanned excisions. Risk factors for tumor recurrence and mortality in patients treated with unplanned excisions were also analyzed. METHODS: Forty-nine patients who underwent unplanned excision at other hospitals and additional wide excision at our hospital between January 2002 and December 2018 were identified. Among them, 42 patients with follow-up for more than 1 year were included in this retrospective study. The relationships between sex, age, tumor depth, histological grade, location, size, surgical margin at additional wide excision, residual tumor, reconstruction, kind of hospital where the primary excision was done (sarcoma vs non-sarcoma center), preoperative examination, chemotherapy, radiation therapy, and oncological outcomes were statistically analyzed. RESULTS: Mean patient age was 57.3 years (15-85 years) and the mean observation period was 72.5 months (14-181 months). This analysis showed 53.8% tumors that underwent unplanned excisions were small (<5 cm) and 70.7% tumors were superficial. Multivariate analysis revealed that a positive margin during additional wide excision was significantly associated with a lower 5-year LRFS (p < 0.01). CONCLUSION: Most of the tumors underwent unplanned excisions were small (<5 cm) and superficial. Surgeons should be aware that a positive margin during additional wide excision is an independent risk factor for local recurrence.

Clinical outcomes of frozen autograft reconstruction for the treatment of primary bone sarcoma in adolescents and young adults.

Age affects the clinical outcomes of cancer treatment, including those for bone sarcoma. Successful reconstruction using frozen autograft after excision of bone sarcoma has been reported; however, little is known about the clinical outcomes of frozen autograft reconstruction according to age. The purpose was to evaluate the clinical outcomes of the frozen autograft reconstruction focusing on skeletally mature adolescents and young adults (AYAs) that was 15 to 39 years of age. A total of 37 AYA patients with primary bone sarcoma on the appendicular skeleton were enrolled in this study. The mean follow-up period was 89 months. The graft survival (GS), overall survival (OS), recurrence-free survival (RFS), complications and the function were retrospectively evaluated using medical records. The 10-year GS, OS, and RFS rates were 76%, 84%, and 79%, respectively. Bone union was achieved with a rate of 94% within 1 year after surgery, and nonunion (n = 1) and fracture (n = 2) were infrequently observed. Graft removal was performed in 7 cases, and the most common reason for the removal was infection (n = 5). The Musculoskeletal Tumor Society score was excellent in 23 cases of the available 29 cases. Frozen autograft reconstruction for AYAs showed excellent clinical outcomes, although the long-term follow-up is required.

Efficacy of perioperative chemotherapy for synovial sarcoma: a retrospective analysis of a Nationwide database in Japan.

BACKGROUND: Synovial sarcoma is an aggressive but chemosensitive soft-tissue tumor. We retrospectively analyzed the efficacy of perioperative chemotherapy for synovial sarcoma with data from the nationwide database, Bone and Soft Tissue Tumor Registry in Japan. METHODS: This study included 316 patients diagnosed with synovial sarcoma between 2006 and 2012. Oncologic outcomes were analyzed using a Cox-hazard regression model. Moreover, the effects of perioperative chemotherapy on outcomes were evaluated using a matched-pair analysis. The oncologic outcomes of patients who did or did not receive chemotherapy were compared (cx + and cx-). RESULTS: Multivariate analysis revealed significant correlations of age (over 40, hazard ratio [HR] = 0.61, p = 0.043), margin status (marginal resection, HR = 0.18, p < 0.001 and intralesional resection, HR = 0.30, p = 0.013 versus wide resection) with overall survival; surgical margin type (marginal resection, HR = 0.14, p = 0.001 and intralesional resection, HR = 0.09, p = 0.035 versus wide resection) with local recurrence; and postoperative local recurrence (HR = 0.30, p = 0.027) and surgical margin (marginal resection, HR = 0.31, p = 0.023 versus wide resection) with distant relapse-free survival. Before propensity score matching, perioperative chemotherapy was mainly administered for young patients and patients with deeper tumor locations, larger tumors, more advanced-stage disease, and trunk location. The 3-year overall survival, local control, and distant relapse-free survival rates were 79.8%/89.3% (HR = 0.64, p = 0.114), 89.6%/93.0% (HR = 0.37, p = 0.171) and 71.4%/84.5% (HR = 0.60, p = 0.089) in the cx+/cx- groups, respectively. After propensity score matching, 152 patients were selected such that the patient demographics were nearly identical in both groups. The 3-year overall survival, local control, and distant relapse-free survival rates were 71.5%/86.0% (HR = 0.48, p = 0.055), 92.5%/93.3% (HR = 0.51, p = 0.436) and 68.4%/83.9% (HR = 0.47, p = 0.046) in the cx+/cx- groups, respectively. CONCLUSION: This large-sample study indicated that the margin status and postoperative disease control were associated directly or indirectly with improved oncologic outcomes. However, the efficacy of perioperative chemotherapy for survival outcomes in synovial sarcoma patients was not proven in this Japanese database analysis.

A Radiological Scoring System for Differentiation between Enchondroma and Chondrosarcoma.

BACKGROUND: It is challenging to differentiate between enchondromas and atypical cartilaginous tumors (ACTs)/chondrosarcomas. In this study, correlations between radiological findings and final diagnosis were investigated in patients with central cartilaginous tumors. METHODS: To evaluate the diagnostic usefulness of radiological findings, correlations between various radiological findings and final diagnoses were investigated in a cohort of 81 patients. Furthermore, a new radiological scoring system was developed by combining radiological findings. RESULTS: Periosteal reaction on X-ray (p = 0.025), endosteal scalloping (p = 0.010) and cortical defect (p = 0.002) on CT, extraskeletal mass (p < 0.001), multilobular lesion (p < 0.001), abnormal signal in adjacent tissue (p = 0.004) on MRI, and increased uptake in bone scan (p = 0.002) and thallium scan (p = 0.027) was significantly correlated with final diagnoses. Based on the correlations between each radiological finding and postoperative histological diagnosis, a radiological scoring system combining these findings was developed. In another cohort of 17 patients, the sensitivity, specificity, and accuracy of the radiological score rates for differentiation between enchondromas and ACTs/chondrosarcomas were 88%, 89%, and 88%, respectively (p = 0.003). CONCLUSION: Radiological assessment with combined radiological findings is recommended to differentiate between enchondromas and ACT/chondrosarcomas.

Delayed Initiation of Treatment Is Associated With Metastasis of Malignant Bone Tumor.

BACKGROUND/AIM: The delayed initiation of treatment is not associated with good clinical outcomes in patients with malignancies. However, few previous studies have examined prognostic factors, including the delayed initiation of treatment, in malignant bone tumors. PATIENTS AND METHODS: One hundred and one patients with malignant bone tumors were enrolled. Univariate and multivariate analyses were performed to identify factors predicting metastasis, including factors that delay the initiation of treatment. RESULTS: The multivariate analysis revealed that high-grade bone malignancy (p<0.01), a >30-day delay in referral to a specialized hospital by a general practitioner (p=0.03), and large tumor size (>77 mm) (p=0.04), were independently associated with metastasis of malignant bone tumors. CONCLUSION: When general practitioners notice a patient with a >77 mm bone tumor, early referral to a specialized hospital within one month might be essential for preventing metastasis.

Osteosarcoma-Derived Small Extracellular Vesicles Enhance Tumor Metastasis and Suppress Osteoclastogenesis by miR-146a-5p.

Osteosarcoma is the most frequent type of primary bone tumor in children and adolescents, thus care for patients with malignant osteosarcoma is strongly required. The roles of small extracellular vesicles (SEVs) in enhancing metastases have been demonstrated in multiple tumors, but they are still poorly understood in osteosarcoma. Hence, this study investigated the effects of SEVs on progression and the tumor microenvironment in mice and patients. In an orthotopic implantation study, we found that osteosarcoma-derived SEVs had the potential to enhance metastases and angiogenesis. In addition, osteosarcoma-derived SEVs decreased the number of mature osteoclasts in vivo. In vitro osteoclastogenesis studies revealed that the inhibition of osteoclast maturation by osteosarcoma-derived SEVs was mediated by suppressing the NF-κB signal pathway. MicroRNA analysis of SEVs from different malignant human osteosarcomas revealed that miR-146a-5p was involved in the inhibition of osteoclastogenesis. In osteosarcoma patients, lower numbers of osteoclasts in biopsy specimens at the first visits were correlated with higher malignancy. These findings indicated that osteosarcoma-derived SEVs enhance distant metastasis of osteosarcomas by inhibiting osteoclast maturation, which may be a useful prognostic marker. This diagnostic method may enable to predict malignancy at early stage, and help to provide optimal care to patients with risk of high malignancy.