BACKGROUND/AIM:Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, and lung metastasis is the major cause of death. Highly metastatic osteosarcoma cells are mechanically softer than low-metastatic cells, and calcium ions are known to regulate cytoskeletal organization and cell stiffness. We tested whether clinically available ion channel blockers could increase the stiffness of LM8 osteosarcoma cells and prevent lung metastasis in vivo. MATERIALS AND METHODS:We evaluated the actin cytoskeletal structure and polymerization in ion channel blocker-treated LM8 cells using actin staining. Cell stiffness was measured using atomic force microscopy. Metastasis-related cellular functions were analyzed using cell proliferation, wound healing, and cell adhesion assays. Furthermore, lung metastasis and tumor volume were measured in LM8-bearing mice treated with an ion channel blocker. RESULTS:Treatment with ion channel blockers significantly increased actin staining intensity and stiffness in LM8 cells compared to that in untreated LM8 cells (p<0.05). The proliferation potential was significantly lower in the amlodipine-treated group (p<0.05). The ion channel blockers treatment group demonstrated significantly higher adhesion than the control group (p<0.05). The migration potential of the disopyramide- and lidocaine-treated groups were lower than that of the control group. Daily intraperitoneal administration of 20 mg/kg amlodipine for five weeks in LM8-bearing mice significantly reduced lung metastasis compared to that in the control group (p<0.05). No significant differences in tumor volume were observed after amlodipine administration. CONCLUSION:Amlodipine could increase tumor cell stiffness and significantly reduce lung metastasis.

BACKGROUND/AIM:The antitumor effects of 5-aminolevulinic acid (5-ALA) radiodynamic therapy (RDT) have been demonstrated in vitro and in vivo in several malignancies. However, its application in bone and soft tissue sarcomas has not been sufficiently explored. In this study, we aimed to elucidate the efficacy of 5-ALA RDT in osteosarcoma cell lines. MATERIALS AND METHODS:In vitro studies utilized human (143B) and mouse (LM8) osteosarcoma cells. Cultured cells were either untreated (control) or exposed to 5-ALA (0-1,000 μg/ml) followed by X-ray irradiation (a single dose of 5 Gy). Cell viability was measured 48 h post-irradiation. Both 143B and LM8 cells were inoculated subcutaneously into the backs of BALB/c mice. Mice were assigned to untreated (control), Rx (irradiation alone), or 5-ALA RDT groups. Mice in the Rx group received X-ray irradiation (5 Gy) after macroscopic tumor formation, while those in the 5-ALA RDT group received 5-ALA (250 mg/kg) intraperitoneally, followed by 5 Gy X-ray irradiation. The mice were sacrificed 14 days after treatment, and changes in tumor volume were evaluated. RESULTS:In vitro, 5-ALA RDT treatment of osteosarcoma cells at 200, 500 and 1,000 μg/ml significantly inhibited cell proliferation at 48 h post-treatment, compared to control cells. In mice injected with osteosarcoma cells, the 5-ALA-RDT group showed a significant reduction in tumor volume compared to the control and Rx groups. No significant changes in body weight or abnormal behavior were observed. CONCLUSION:5-ALA RDT demonstrated significant anti-tumor effects in both in vitro and in vivo osteosarcoma models. These findings suggest its potential as a therapeutic approach for osteosarcoma.

BACKGROUND/AIM:Pediatric osteosarcoma is a rare and aggressive malignancy with limited treatment options in cases of progression or metastasis. Regorafenib is an oral multikinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and other kinases, currently approved in Japan for certain gastrointestinal cancers. Its clinical use in osteosarcoma, especially in pediatric patients, has not been well established. PATIENTS AND METHODS:We retrospectively analyzed six pediatric patients with advanced osteosarcoma who were treated with regorafenib at our institution. All patients had previously received standard treatment, including neoadjuvant and adjuvant chemotherapy as well as surgery, and were considered to have disease progression or resistance prior to regorafenib administration. Clinical background, treatment response, adverse events, and progression-free survival (PFS) were evaluated. Tumor response was assessed using RECIST criteria, and adverse events were graded according to CTCAE v5.0. RESULTS:The average age was 16 years (range=12-18 years), and all patients had received prior surgery and chemotherapy. Regorafenib was administered at adult equivalent doses, with dose reductions required in 3 of 6 patients. Four patients (66.7%) achieved stable disease for at least eight weeks. The longest PFS exceeded 12 months. Common toxicities included diarrhea and hematuria; no grade ≧3 adverse events were observed. All patients underwent genomic testing to guide treatment planning. CONCLUSION:This case series suggests that regorafenib may provide disease control with acceptable safety in pediatric patients with advanced osteosarcoma. Further studies are needed to evaluate its efficacy and tolerability in this population as well as in adult patients.

Background/Objectives: To elucidate the role of the CALLY index in 172 adult patients with primary soft tissue sarcoma (STS) and to evaluate whether the CALLY index is superior to the modified Glasgow prognostic score (mGPS) and prognostic nutrition index (PNI). Methods: The study cohort included 100 men and 72 women with a mean age of 63 years. Receiver operating characteristic (ROC) curve analysis was performed to determine the threshold value of the CALLY index for identifying the risk of identifying oncological events at 2 years. Results: ROC analysis identified 2.07 as the threshold of the CALLY index for predicting the risk of identifying oncological events at 2 years. The 5-year disease-specific survival (DSS) rate was 50.9% in patients with a lower CALLY index compared to 84% in those with a higher CALLY index. All patients with mGPS scores of 1 or 2 had lower CALLY indices, whereas all patients with a higher CALLY index had an mGPS score of 0. Patients with a lower CALLY index and mGPS of 0 had better DSS than those with a lower CALLY index and mGPS of 1 or 2. No substantial differences in DSS and disease-free survival (DFS) were observed between patients with a higher CALLY index and those with a lower CALLY index and an mGPS of 0. Conclusions: The CALLY index is a useful marker for predicting oncological outcomes in patients with primary STS. In particular, the CALLY index was a statistically significant prognostic variable for survival in patients with UPS and DDLPS individually. However, we suggest that the mGPS remains a reliable system for identifying patients with primary STSs who are at a high risk of death and relapse because we showed the significant difference for survival and event-free survival between the patients with mGPS of 1 and 2.

BACKGROUND/AIM:5-Aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PpIX), a radiosensitizer that selectively accumulates in tumor cells. Radiodynamic therapy (RDT) using 5-ALA has demonstrated antitumor effects after systemic administration; however, its efficacy after local administration remains unclear. This study evaluated the therapeutic efficacy of RDT using locally administered 5-ALA in an osteosarcoma xenograft mouse model. MATERIALS AND METHODS:The murine osteosarcoma cell line (LM8) was subcutaneously inoculated into the backs of 5-week-old male BALB/c mice. After tumor establishment (tumor diameter >10 mm), the mice were randomly assigned to three groups (n=5 per group): control (no treatment), irradiation alone (Rx group; single dose of 5 Gy), and 5-ALA RDT group. In the RDT group, 5-ALA (25 mg/kg equivalent; 500 μg/ml, 1 ml) was locally administered to the peritumoral region, followed by a single dose of 5 Gy X-ray irradiation. Tumor volume and body weight were measured over two weeks. The primary outcome was the change in tumor volume. RESULTS:Fourteen days after treatment, tumor growth was significantly suppressed in the 5-ALA RDT group compared to the control and irradiation groups. No significant differences in body weight were observed among the groups, and no abnormal behaviors were detected. Radiodynamic therapy with locally administered 5-ALA demonstrated significant antitumor effects in a murine model of osteosarcoma. Despite the reduced dose compared to systemic administration, local delivery effectively enhanced the radiosensitizing effect. CONCLUSION:The local administration of 5-ALA represents a promising and less toxic therapeutic strategy for osteosarcoma.

Background/Objectives: Chemotherapy is recommended for patients with advanced soft tissue sarcoma (STS). However, chemotherapy is less aggressive in elderly patients than in younger patients owing to comorbidities and other health problems. This multicenter study aimed to examine the outcomes of elderly patients treated with chemotherapy for advanced STS. Methods: The study cohort included 60 men and 71 women with a mean age of 73 years. The mean follow-up duration was 22.9 months. Results: As first-line treatment, the doxorubicin-containing regimen was the most frequently used. Dose reduction was more frequent in patients aged ≥ 75 years than in those aged ≤ 74 years. Complete response occurred in two patients and partial response in eight patients. The objective response rate was 8.2%. The 1- and 2-year survival rates after first-line chemotherapy were 61.8% and 40.2%, respectively. The median survival time was 19 months. In multivariate analysis, patients with performance status (PS) 2 or 3 had poorer survival than those with PS 0 or 1. The median survival times for patients with PS 0 or 1 and PS 2 or 3 were 22.1 and 4.3 months, respectively. Among 131 patients, no fatal adverse events occurred, although chemotherapy was discontinued due to adverse events in 28 patients. Conclusions: Chemotherapy for advanced STS in elderly patients may be effective in those with good PS, although it should be considered to evaluate the benefits and risks of cytotoxic chemotherapy.

Background/Objectives: The aim of this study was to review the clinical course of schwannoma in 176 patients and elucidate the clinical outcome in a patient who received surgical treatment and one who did not. Methods: Between August 2006 and December 2021, 176 patients with solitary and sporadic schwannomas were enrolled in our institution. There were 94 men and 82 women, with a mean age of 57 years. During follow-up, 76 patients received surgical treatment, and the remaining 100 did not. Results: The mean tumor size at initial presentation was 30 mm. The major tumor locations were the thigh, lower leg, upper arm, and forearm. The major nerves affected by the schwannoma were the intramuscular branch, sciatic nerve, and ulnar nerve. At least one symptom in addition to a palpable mass was observed in 133 patients (76%). The variables that indicated surgical treatment were tumor size at initial presentation, age, and any other existing symptoms. After surgery, pain-related symptoms including pain, irradiated pain and tenderness were resolved completely in 42 of 44 patients (95%) who had displayed them preoperatively. Neurological deficit was observed in 26 patients (34%). Among the 26 patients with neurological deficit, neurological sensory deficit was observed in 23 patients, and the remaining three had sensory and motor deficits. Multivariate analysis showed that patients with major nerve schwannoma, those with paresthesia preoperatively, and those who developed preoperative symptoms and had undergone surgery had a higher risk of the development of postoperative neurological deficit. Conclusions: Our findings should be considered while planning surgery and obtaining informed consent.

BACKGROUND:Soft tissue sarcomas (STSs) are a diverse group of rare malignant tumors accounting for <1% of all human tumors. Almost 50% of patients with STS develop metastatic disease, mainly within 3 years of initial diagnosis. Lung metastasis occurs in 20%-30% of STS cases, while bone metastasis is rare. PATIENTS AND METHODS:We investigated tumor characteristics and clinical outcomes in 59 patients with STS who developed bone metastases. RESULTS:A total of 21 patients had solitary bone metastasis: two in the extremity, 11 in the vertebral body, and eight in the trunk. Around 38 patients had multiple bone metastases: 18 with extremity bone involvement and 20 with no extremity bone involvement. Fourteen patients developed complicated bone metastases with distant extrapulmonary metastases. Seven patients had no distant metastases other than bone; that is, the bone was the first distant metastasis. The 5-year disease-specific survival (DSS) rate after primary treatment was 45.1%. The median 5-year DSS after bone metastasis was 28.1 months. The 5-year DSS rate was 55.6% in nine patients who underwent radical local treatment for solitary bone metastases. The 5-year DSS rate was 14.7% in 50 patients who did not undergo local radical treatment for bone metastases, with a significant correlation. CONCLUSION:Patients with bone metastases from STS had a relatively good prognosis after bone metastases. Solitary bone metastases can be aggressively treated. Although nearly half of the patients received bone-modifying agents, the effectiveness of these therapeutics warrants further investigation.

Soft tissue tumors arise in soft tissues in the body. Because the soft tissue tumor is one of the rare cancers, it is difficult to diagnose and treat in general hospitals. This study focuses on obtaining a quantitative index that physicians can use to build a treatment plan for soft tissue tumors based on the patient’s survival period or risk of experiencing clinical events in the future. This paper proposes a convolutional neural network-based patient’s survival period prediction method using pathological images. Since soft tissue tumors are rare cancers, the number of subjects is not enough to train a complex CNN model. We used the mean-variance loss to tackle the regression task predicting the survival period using ResNet18, a classification CNN model. Furthermore, we improved the soft label to efficiently train the classification CNN for the regression task. Experiments on 44 whole slide images of 44 patients showed that the improved soft label called fit label achieved the lowest mean absolute error of 6.5 months and the highest concordance index of 0.893. From these results, the proposed method can be used to evaluate the risk level of a patient with soft tissue tumors.

Soft tissue sarcoma (STS) is a rare and heterogeneous disease, which can result in surgeons not considering STS as a differential diagnosis when they encounter a lump. However, unplanned excision (UE) often occurs in nonspecialized sarcoma centers. Before re-excision (RE) after UE, radiological examinations such as magnetic resonance imaging (MRI) should be performed to determine the surgical margin and conduct a pathological evaluation of the UE. However, differentiating between residual tumor and postsurgical changes remains challenging because of the presence of postoperative edema, hematoma, and seroma on MRI. Propensity score matching analysis showed that patients with STS who underwent RE after UE did not have higher mortality or local recurrence rates than those who underwent planned excision (PE), while RE often requires reconstruction procedures. From the patient’s perspective, one operation (PE) is better than two (UE and RE) because it reduces hospital stays and time away from work. Continuous education about STS is necessary for all surgeons to reduce the incidence of UE.

BACKGROUND:Although the significance of preoperative denosumab administration for giant cell tumor of bone (GCTB) is still controversial, sporadic reports have suggested a clinical benefit of administration prior to surgery for spinal GCTB. In this retrospective, multi-institutional study, we assessed the effects of preoperative denosumab administration for spinal GCTB. METHODS:Ten cases of GCTB in the spine with preoperative denosumab administration (the denosumab group) and 19 cases without preoperative denosumab administration (the control group) were included. Oncological outcomes (local recurrence, distant metastasis, and overall survival), duration of the surgery, intraoperative blood loss, functional outcomes as evaluated by the Frankel classification, perioperative complications, adverse events associated with denosumab administration, and margin status in resection cases were surveyed. RESULTS:The median frequency of preoperative denosumab administration was four times in the denosumab group. Curettage against resection and no preoperative denosumab administration were revealed as independent risks for local recurrence. Preoperative denosumab administration significantly reduced intraoperative blood loss. It also resulted in significantly better postoperative function. Periodontitis as an adverse effect of denosumab administration was found only in two cases in the control group, where it was applied for controlling local recurrence. Cases with local recurrence showed worse function at the final follow-up, suggesting the significant impact of local recurrence on function. The negative margin rate was significantly higher in the denosumab group. No significant difference was noted in the risk for metastasis and lethal events, duration of surgery, and incidence of postoperative complications between the two groups. CONCLUSIONS:Preoperative denosumab administration resulted in better local control, reduced intraoperative blood loss, and better function. The present data suggest that it has a clinical benefit in the treatment of spinal GCTB.

Trabectedin extravasation can cause significant soft tissue disorders. Early surgical intervention has been recommended in the event of chemotherapeutic extravasation; however, treatment tends to remain conservative. Trabectedin is a vesicant drug that is associated with a risk of delayed tissue damage; therefore, leaks should be promptly stopped. Complications associated with central venous (CV) ports include infection, catheter damage and obstruction, which can lead to trabectedin extravasation. In the present case report, a 61-year-old woman who received trabectedin treatment for multiple liver and lung metastases is described. Extravasation developed from a CV port in the right chest during the third course of treatment and swelling was the only apparent symptom at that time. Trabectedin was immediately discontinued and she was administered steroids subcutaneously. Erythema, induration and tenderness appeared on day 1 after extravasation, but skin symptoms were not subsequently exacerbated. The central region of the erythema became crusted ~1 month after extravasation. When the skin condition had settled at 2 months post-extravasation, the patient underwent port removal, debridement and port reattachment.

Background:Osteosarcoma (OS), the most common pediatric bone tumor, faces challenges with frequent relapse despite treatment advances. Identifying early diagnostic biomarkers and therapeutic targets is critical. The purpose of this study was to investigate the novel biomarkers for OS, and we also aimed to explore whether these biomarkers could potentially serve as the therapy targets. Methods:Integrated analysis combined three Gene Expression Omnibus (GEO) datasets (GSE42352, GSE126209, GSE12865) and TARGET-OS clinical-transcriptomic data (n=88). Immune-related genes from ImmPort (1,793 genes) were analyzed alongside differentially expressed genes (DEGs) identified via sva batch correction. Functional enrichment used clusterProfiler, while machine learning [eXtreme Gradient Boosting (XGB), random forest (RF), generalized linear model (GLM), support vector machine (SVM)] models were built with caret, xgboost, and kernlab. Prognostic genes were screened via univariate Cox regression (P<0.05). Key genes intersecting SVM and Cox results were validated via package for receiver operating characteristic (pROC), survival analysis, competing endogenous RNA (ceRNA) network (Cytoscape), immune infiltration (CIBERSORT), drug sensitivity (GDSC), and quantitative polymerase chain reaction (qPCR). Results:Differential analysis identified 1,370 DEGs (748 upregulated, 622 downregulated), intersecting with immune-related genes to yield 174 OS-linked immune-DEGs. Enrichment highlighted cytokine-PI3K-Akt pathways. Machine learning prioritized 10 genes, with MASP1 showing highest diagnostic accuracy [area under the curve (AUC) =0.903, 95% confidence interval (CI): 0.769-0.993]. Univariate Cox linked NRP3, STC2, ANGPT1, MASP1, SDC4, NEDD4, TYROBP to prognosis (P<0.05). Intersection identified MASP1 as the core gene, significantly downregulated in OS tissue. Survival analysis across GEO/TARGET confirmed higher MASP1 expression correlated with better outcomes (P<0.05). MASP1 inversely correlated with resting CD4+ T-cell infiltration (r=-0.14, P=0.04), a poor prognostic marker. Drug sensitivity analysis associated MASP1 with enhanced response to doxorubicin, vinblastine, gemcitabine, and sorafenib. qPCR validated MASP1 downregulation in OS samples. Conclusions:MASP1 is a promising diagnostic biomarker and therapeutic target for OS. These findings could help to improve patient prognosis and the treatment response. Further studies should be conducted explore MASP1 clinical applications.

Background: Few studies have compared the clinical outcomes of patients with pelvic bone sarcomas treated surgically and those treated with particle beam therapy. This is a multicenter retrospective cohort study which compared the clinical outcomes of patients with pelvic bone sarcoma who underwent surgical treatment and particle beam therapy in Japan. Methods: A total of 116 patients with pelvic bone sarcoma treated at 19 specialized sarcoma centers in Japan were included in this study. Fifty-seven patients underwent surgery (surgery group), and 59 patients underwent particle beam therapy (particle beam group; carbon-ion radiotherapy: 55 patients, proton: four patients). Results: The median age at primary tumor diagnosis was 52 years in the surgery group and 66 years in the particle beam group (P < 0.001), and the median tumor size was 9 cm in the surgery group and 8 cm in the particle beam group (P = 0.091). Overall survival (OS), local control (LC), and metastasis-free survival (MFS) rates were evaluated using the Kaplan-Meier method and compared among 116 patients with bone sarcoma (surgery group, 57 patients; particle beam group, 59 patients). After propensity score matching, the 3-year OS, LC, and MFS rates were 82.9% (95% confidence interval [CI], 60.5-93.2%), 66.0% (95% CI, 43.3-81.3%), and 78.4% (95% CI, 55.5-90.5%), respectively, in the surgery group and 64.9% (95% CI, 41.7-80.8%), 86.4% (95% CI, 63.3-95.4%), and 62.6% (95% CI, 38.5-79.4%), respectively, in the particle beam group. In chordoma patients, only surgery was significantly correlated with worse LC in the univariate analysis. Conclusions: The groups had no significant differences in the OS, LC, and MFS rates. Among the patients with chordomas, the 3-year LC rate in the particle beam group was significantly higher than in the surgery group. (c) 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Synovial sarcoma (SS) is the most common soft tissue sarcoma in children and adolescents. Despite the availability of new agents such as pazopanib and trabectedin, the prognosis after recurrence remains poor. Adoptive cell therapy is an emerging therapeutic strategy based on the modulation, manipulation, and selection of autologous T-cells in vitro to overcome immune system tolerance to tumor cells. Cancer-testis antigens are particularly attractive targets for immune therapy because male germ cells lack human leukocyte antigen class I molecules, limiting T-cell responses triggered by antigen presentation. T-cell receptor (TCR) engineered T-cell therapy targeting NY-ESO-1 and MAGE-A4 holds significant promise because of the high positive expression of these antigens in tumors. This approach facilitates the reprogramming of T lymphocytes by a transgenic TCR through gene transfer of TCR α and β chains specific to tumor antigens, offering potential therapeutic advances for patients with advanced SS. Clinical trials of TCR-engineered T-cell therapy targeting NY-ESO-1 and MAGE-A4 have been conducted, with an objective response rate reported to be 40–60

Background Procedural techniques such as dissection and separation of blood vessels or nerves from the tumor for preserving limbs and functions involves high surgical difficulty. We hypothesized the relation of vessel and/or nerve preservation to surgical time and blood loss, accurately reflecting surgical difficulty. In this study, we elucidated the variables affecting surgical time and intraoperative bleeding in patients with malignant soft tissue tumors who did not undergo any reconstruction after tumor resection.Methods We included 153 patients with malignant oft tissue tumors in the trunk (n = 72), thigh (n = 68), and upper arm (n = 13) at nine institutions. We analyzed the possible predictive variables affecting surgical time and intraoperative bleeding.Results Overall, the study included 153 patients (85 men and 68 women) with a mean age of 65 years. The tumors were primary soft tissue sarcoma (STS) (n = 114), local recurrent STS (n = 25), and soft tissue metastasis (n = 14). The median number of participating surgeons was three. The mean and median surgical time were 144.6 and 123 min, respectively. The mean and median intraoperative bleeding were 157.1 and 55 mL, respectively. Tumor size, depth, dissection and separation of blood vessels from the tumor, dissection and separation of nerve from the tumor, and the number of participating surgeons were significantly related to the surgical time and intraoperative bleeding.Conclusions The procedure of dissection and separation of blood vessels and nerves from the tumor were related to surgical time and intraoperative bleeding in patients with malignant soft tissue tumors, especially large and deep tumors. The procedure of dissection and separation of blood vessels and nerves from the tumor, which involves high surgical difficulty, were related to surgical time in patients with malignant soft tissue tumors.

The primary aim of this study was to compare the surgical invasiveness of internal fixation for pathological fractures caused by metastatic bone tumors with that for traumatic fractures. The secondary aim was to identify factors contributing to the complexity of surgeries for metastatic bone disease and provide insights for improving surgical strategies by analyzing operative time and blood loss. Patients undergoing internal fixation for femoral fractures at 10 institutions between January 2021 and December 2023 were included. Traumatic and metastatic pathological fractures were analyzed, excluding patients aged <18 years and those with benign or atypical fractures. Factors influencing blood loss and operative time were assessed using univariate regression and multivariate modeling (P < 0.05). A total of 275 patients (male = 97, female = 178) with a mean age of 76 years were included. Patients had 230 traumatic and 45 metastatic fractures, with proximal fractures being the most common (n = 225). Intramedullary nailing was the predominant fixation method (n = 231). Blood loss and operative times were significantly affected by the fracture cause, site, and reduction procedures (P < 0.05). Metastatic, distal, or diaphyseal fractures and reduction procedures resulted in higher blood loss and longer operative times. Multivariate analysis confirmed these factors as significant predictors. Surgeries for metastatic fractures are more invasive than those for traumatic fractures because of compromised bone integrity and procedural complexity. Operative time is a key indicator of surgical invasiveness, highlighting the need for tailored surgical approaches to manage metastatic bone disease effectively.

Introduction: Osteochondromas are benign tumors that arise primarily in the metaphyseal region of long bones. The malignant transformation rate is estimated to be less than 1% and 1–3% in solitary and multiple osteochondromas, respectively. Transformation to osteosarcoma is very rare. Little information is available on treatment or outcome. A rare case of osteosarcoma arising from hereditary multiple osteochondromas of the right iliac bone is reported. Case Presentation: A 66-year-old woman presented with recurrent right abdominal pain. Computed tomography (CT) showed a mass protruding into the pelvic cavity, 9 cm × 7 cm × 7 cm, with bone destruction and internal calcification in the right iliac bone. A CT-guided biopsy was performed, and the diagnosis was osteosarcoma. After one course of chemotherapy with doxorubicin and ifosfamide, extensive resection of the tumor was performed. The pathology showed proliferation of highly pleomorphic dysplastic cells with bone formation inside the tumor just below the osteochondroma tissue, which led to the diagnosis of osteosarcoma arising from the osteochondroma. Three years after surgery, there was no evidence of recurrence or metastasis, and the patient was able to walk unassisted. Conclusion: A case of osteosarcoma arising from an iliac lesion of hereditary multiple osteochondromas was described. Although no recurrence or metastasis has been observed 3 years after surgery, further follow-up is necessary due to the short time after surgery.

(1) Background: Exosomal PD-L1 has garnered attention owing to its role in instigating systemic immune suppression. The objective of this study is to elucidate whether bone and soft tissue sarcoma cells possess the capacity to secrete functionally active exosomal PD-L1 and whether radiotherapy (RT) induces the exosomal PD-L1 release. (2) Methods: Human osteosarcoma cell line 143B and human fibrosarcoma cell line HT1080 were utilized. Exosomes were isolated from the culture medium and blood via ultracentrifugation. The expression of PD-L1 on both tumor cells and exosomes was evaluated. The inhibitory effect on PBMC was employed to assess the activity of exosomal PD-L1. Post radiotherapy, changes in PD-L1 expression were compared. (3) Results: Exosomal PD-L1 was detected in the culture medium of tumor cells but was absent in the culture medium of PD-L1 knockout cells. Exosomal PD-L1 exhibited an inhibitory effect on PBMC activation. In tumor-bearing mice, human-derived exosomal PD-L1 was detected in the bloodstream. Following radiotherapy, tumor cells upregulated PD-L1, and human-derived exosomal PD-L1 were detected in the bloodstream. (4) Conclusions: Exosomal PD-L1 emanates from bone and soft tissue sarcoma cells and is disseminated into the circulatory system. The levels of PD-L1 in tumor cells and the release of exosomal PD-L1 were augmented after irradiation with RT.

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. (c) 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.