Pedicled flap transfer after chest wall malignant tumor resection and potential risk of postoperative respiratory problems for patients with low FEV1.0.

Introduction: Musculoskeletal transfer for chest wall tissue defects is a crucial method, and pedicled flaps around the chest wall are preferred in terms of location and simplicity of transfer. These require special care because of complications such as partial necrosis, fistula, wound dehiscence, infection, hematoma and restricted function of the arm or shoulder. However, studies of respiratory function are rare. In the present study, we investigated the complications including respiratory problems after wide resection for malignant chest wall tumors with musculoskeletal pedicle transfer. Methods: A total of 13 patients (15 operations) who underwent wide resection of primary, recurrent, or metastatic malignant chest wall tumors and musculoskeletal pedicle transfer for coverage of tissue defects were enrolled in the present study. A retrospective review of all patients was performed using data collected from hospital records and follow-up information. The complications of musculoskeletal transfer after chest wall wide resection, including respiratory problems, are evaluated. Results: Rib or sternal resection was performed in 12 operations, and only soft tissue resection was performed in 3 operations. Latissimus dorsi (LD) pedicle transfer was performed in 13 operations, and pectoralis major (PM) pedicle transfer was performed in 2 operations; basically, wounds were closed primarily. Surgical complications were observed following 5 of the 15 operations (33.3%). Respiratory complications were seen in 7 of the 15 operations (46.7%). Patients with respiratory complications showed significantly lower preoperative FEV1.0% values than those without respiratory complications (p = 0.0196). Skin resection area tended to be higher in the complication group than in the no complication group (p = 0.104). Discussion: Pedicled myocutaneous flap transfers such as LD, PM, and rectus abdominus can be used following multiple resections. After harvesting LD or PM, the wound can be closed primarily for an 8-10-cm skin defect in patients with normal respiratory function. However, for patients with low FEV1.0%, after primary closure of LD or PM transfer for wide soft tissue defects, attention should be paid to postoperative respiratory complications.

The Combined Use of Inflammation Markers, Modified Glasgow Prognostic Score, and Sarculator Nomogram in Extremity Soft Tissue Sarcoma: A Multicenter Observational Study.

BACKGROUND: Sarculator is a validated nomogram designed to predict overall survival (OS) in extremity soft tissue sarcoma (STS). Inflammation plays a critical role in cancer development and progression. There were no reports which investigated the relationship between Sarculator and inflammation. METHODS: A total of 217 patients with extremity STS were included. The Sarculator-predicted 10-year probability of OS (pr-OS) was stratified into two subgroups: lower risk (10-year pr-OS ≥ 60%) and higher risk (10-year pr-OS < 60%). The modified Glasgow prognostic score (mGPS) varied from 0 to 2. RESULTS: Out of the 217 patients, 67 were classified as higher risk, while 150 were lower risk. A total of 181 patients had an mGPS of 0, and 36 had a score of 1 or 2. The 5-year OS was 83.3%. When patients were divided into two groups according to the 10-year pr-OS, those with a higher risk had poorer OS than those with a lower risk. Among the patients with a higher risk, those with an mGPS of 1 or 2 had poorer OS compared to those with a score of 0. CONCLUSIONS: The mGPS could potentially play an important role in identifying patients who are at high risk of death and metastasis in the higher-risk group on the Sarculator.

Screening for Synergistic Reagents With Pazopanib Against Osteosarcoma Using a Compound Library.

BACKGROUND/AIM: Osteosarcoma (OS) is the most common malignant bone tumor. As the same agents have been in use since the mid-1970s, new therapeutic approaches are needed to improve prognosis. Pazopanib (PZP) has already demonstrated marked antitumor activity clinically and can be effective in patients with metastatic OS. We investigated the combination treatment of candidate agents with PZP and examined effects on tumor growth using an in vivo model. MATERIALS AND METHODS: A library of 324 compounds was used. MG63 OS cells were treated with PZP and each compound. Cell viability was measured. The antiproliferative effects of compound combination on four OS cell lines was tested. Cell signaling was evaluated by western blot analysis. In vivo antitumor testing was performed using 143B-bearing mice. RESULTS: The screening process identified crizotinib (CRZ) as the most effective drug for combination with PZP. The combination of PZP and CRZ demonstrated effects compared to control or single therapy. Cell signal investigation showed that dual therapy down-regulated c-MYC, p-AKT, p-STAT3, p-cyclin D1 and survivin and up-regulated cleaved caspase-3 and cleaved PARP compared to control or single therapy. In vivo analysis showed dual therapy achieved synergic effects for tumor growth compared to control or single-treatment groups. No significant difference in the change in body weight was observed among groups. CONCLUSION: Combined use of PZP and CRZ offers synergic anti-tumor effects against OS, inducing apoptosis in vitro and in vivo by down-regulating AKT and STAT3. Our data suggest that these agents can be used for patients clinically.

The Effect of Photodynamic Therapy Using 5-Aminolevulinic Acid in Bone and Soft Tissue Sarcoma Cells.

BACKGROUND/AIM: 5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of protoporphyrin IX (PpIX). Following light irradiation, the PpIX generates reactive oxygen species (ROS) in the presence of oxygen. Increased ROS levels can cause apoptotic cell death and necrosis of targeted cancer cells. This study examined whether photodynamic therapy using 5ALA (5-ALA PDT) could be used as a potential adjuvant therapy for bone and soft tissue sarcomas. MATERIALS AND METHODS: The human osteosarcoma (143B), mouse osteosarcoma (LM8), human fibrosarcoma cell (HT1080) cell lines were used. In vitro, cultured cells were exposed to 5-ALA at various concentrations followed by strobe scope light irradiation for 10 min as 5-ALA PDT. Cell viability was then measured. In vivo, each tumor cell line was inoculated subcutaneously into the backs of mice. In the 5-ALA PDT group, 5-ALA (250 mg/kg) was administered intraperitoneally followed by light irradiation. Change in tumor volume by 5-ALA PDT were primarily evaluated. RESULTS: In vitro, treatment of sarcoma cells with 100 and 200 µg/ml 5-ALA PDT significantly inhibited cell proliferation at 24 and 48 h compared with the group treated with 0 and 10 µg/ml 5-ALA PDT. In vivo, in all cell lines, a significant inhibition of the tumor volume was observed in the 5-ALA-PDT group as compared to that in control, strobe scope light, and 5-ALA groups. CONCLUSION: 5-ALA PDT effectively inhibited proliferation of bone and soft tissue sarcoma cell lines. Further in vivo research using other subtypes of bone and soft tissue sarcoma is warranted to confirm the applicability in the clinical setting.

C­reactive protein and related predictors in soft tissue sarcoma (Review).

C-reactive protein (CRP) is a useful predictor of poor survival in patients with several types of cancer because inflammation is strongly associated with cancer progression. The production of CRP in hepatocytes appears to be primarily induced at the transcriptional level following the elevation of circulating interleukin-6 (IL-6), which is produced by various cell types, including cancer cells and cancer-associated fibroblasts. Serum CRP levels are associated with serum IL-6 levels in patients with soft tissue sarcoma (STS). Additionally, patients with elevated CRP levels had worse oncological outcomes than those with normal CRP levels. It has been attempted to combine CRP levels with other inflammatory or immune markers, and the utility of this has been demonstrated. Therefore, a novel treatment strategy should be developed for patients with STS with elevated CRP levels. The present review aimed to clarify the role of CRP levels and related tools in predicting clinical outcomes in patients with STS.

Histological Assessment of Synovial Sarcoma Before and After TCR-T Cell Therapy and Cryoablation: A Case Report.

BACKGROUND/AIM: Cancer/testis antigens (CTAs) are well-known molecular targets with expression restricted to testicular germ cells and malignant tumors. T-cell receptor (TCR)-engineered T-cell (TCR-T) therapy against CTAs in patients with sarcoma has shown substantial progress, but resistance to TCR-T therapy remains a critical problem. In this report, we present a case of synovial sarcoma treated with TCR-T therapy targeting the New York-esophageal squamous cell carcinoma (NY-ESO)-1 protein. Histological findings were compared before and after TCR-T therapy and before and immediately after cryoablation. CASE REPORT: A 68-year-old man received additional wide resection for synovial sarcoma in the left leg. Due to multiple metastases, he was enrolled in a clinical trial of TCR-T therapy for NY-ESO-1. The tumor demonstrated a 34.9% reduction in diameter. However, disease progression occurred by day 84 after TCR-T therapy. Six months after disease progression, cryoablation was performed for right posterior rib lesion and tumor specimens were obtained by needle biopsy both before and immediately after cryoablation. Ten months after the diagnosis of disease progression, the patient died. Expression levels of NY-ESO-1, human leukocyte antigen, and immune checkpoint proteins remained unchanged before and after TCR-T therapy. Beta catenin was up-regulated in recurrent tumor tissues after TCR-T therapy compared to levels observed before TCR-T therapy. Immediately after cryoablation, immunoreactivity for NY-ESO-1 showed a slightly reduction. CONCLUSION: Up-regulation of beta-catenin in synovial sarcoma with recurrence after TCR-T therapy may be involved in T-cell exclusion and resistance to TCR-T therapy. Needle biopsy after cryoablation can be performed with sufficient pathological diagnostic accuracy including immunostaining.

Clinical Outcome in Patients With High-grade Soft-tissue Sarcoma Receiving Prosthetic Replacement After Tumor Resection of the Lower Extremities: Tokai Musculoskeletal Oncology Consortium Study.

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

Gastric metastasis in patients with leiomyosarcoma: A case report.

Soft tissue sarcomas (STS) are very rare tumors, accounting for <1% of all malignancies. Leiomyosarcoma (LMS), accounts for 10-20% of STS. Gastric metastasis of LMS is extremely rare, and only a few cases have been reported. In the present report, two clinical cases of LMS with gastric metastasis. In the present cases, the metastases presented as a solitary lesion and was located in the upper body anterior wall in case 1, and body-greater curvature in case 2. It is debatable whether to perform any local treatment for gastric metastasis due to its poor prognosis. However, the progression of metastatic cancer in the stomach can lead to gastric bleeding, abdominal pain, and dysphagia, which may further shorten survival and decrease a patient's quality of life. Therefore, metastasectomy was performed in the present cases. This should be considered if digestive tract symptoms occur during the treatment of LMS.

What is a useful marker for predicting survival in patients with high-grade soft tissue sarcoma who have non-inflammatory conditions?

BACKGROUND: The modified Glasgow prognostic score (mGPS) is a reliable system for identifying patients at high risk of death among patients with soft tissue sarcoma (STS). The scoring systems use a combination of C-reactive protein (CRP) and albumin levels. Although patients with high-grade STS are at risk of metastasis and death, even if their mGPS is 0, the prognostic indicators in these patients are unknown. Therefore, we investigated useful prognostic indicators for survival and the development of metastasis in patients with high-grade STS and an mGPS of 0. METHODS: One hundred and four patients with CRP and albumin levels of <1.0 mg/dl and >3.5 g/dl, respectively, indicating an mGPS of 0, were included. The mean follow-up period was 79 months. RESULTS: The 5-year disease-specific survival (DSS) rate was 79.2%. Cox proportional analysis showed that tumor size and absolute neutrophil count (ANC) were prognostic variables in multivariate analyses. Patients with higher ANC (ANC>3370/µl) had a worse DSS than those with lower ANC. The 5-year DSS was 74.7% vs. 91.7%, respectively (p = 0.0207). The 5-year metastasis-free survival was 67.2%. Tumor size and ANC remained significant variables for predicting the development of metastasis in the multivariate analysis. Patients with higher ANC had a worse metastasis-free survival than those with lower ANC. The 5-year metastasis-free survival was 59.5% vs. 87.3%, respectively (p = 0.00269). CONCLUSIONS: When patients with high-grade STS have an mGPS of 0, the ANC and tumor size should be carefully evaluated. A higher neutrophil count and larger tumor size may increase the risk of metastasis development.

Artifactual hypoglycaemia may be common in patients with soft tissue sarcoma who received pegfilgrastim-supported chemotherapy.

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.

Full-thickness chest wall resection for malignant chest wall tumors and postoperative problems.

Background: Chest wall malignant tumor (including primary and metastatic lesions) is rare, representing less than 5% of all thoracic malignancies. Local control of chest wall malignancies requires wide resection with tumor-free margins. These requirements increase the risk of thoracic cavity failure and subsequent pulmonary failure. The restoration strategy for chest wall defects comprises chest wall reconstruction and soft-tissue coverage. Various reconstruction methods have been used, but both evidence and guidelines for chest wall reconstruction remain lacking. The purposes of this study were to collate our institutional experience, evaluate the outcomes of full-thickness chest wall resection and reconstruction for patients with chest wall malignant tumor, and identify problems in current practice for chest wall reconstruction with a focus on local control, complications, pulmonary function and scoliosis. Methods: Participants comprised 30 patients with full-thickness chest wall malignant tumor who underwent chest wall resection and reconstruction between 1997 and 2021 in Mie University Hospital. All patients underwent chest wall resection of primary, recurrent or metastatic malignant tumors. A retrospective review was conducted for 32 operations. Results: Recurrence was observed after 5 operations. Total 5-year recurrence-free survival (RFS) rate was 79.3%. Diameter ≥5 cm was significantly associated with poor RFS. The postoperative complication rate was 18.8%. Flail chest was observed with resection of ≥3 ribs in anterior and lateral resections or with sternum resection without polyethylene methylmethacrylate reconstruction. Postoperative EFV1.0% did not show any significant decrease. Postoperative %VC decreased significantly with resection of ≥4 ribs or an area of >70 cm2. Postoperative scoliosis was observed in 8 of 28 patients. Posterior resection was associated with a high prevalence of scoliosis (88.9%). Conclusion: With chest wall reconstruction, risks of pulmonary impairment, flail chest and scoliosis were significantly increased. New strategies including indications for rigid reconstruction are needed to improve the outcomes of chest wall reconstruction.

A Novel Approach to Reducing Lung Metastasis in Osteosarcoma: Increasing Cell Stiffness with Carbenoxolone.

AIM: Primary malignant bone tumor osteosarcoma can metastasize to the lung. Diminishing lung metastasis would positively affect the prognosis of patients. Our previous studies demonstrated that highly metastatic osteosarcoma cell lines are significantly softer than low-metastasis cell lines. We therefore hypothesized that increasing cell stiffness would suppress metastasis by reducing cell motility. In this study, we tested whether carbenoxolone (CBX) increases the stiffness of LM8 osteosarcoma cells and prevents lung metastasis in vivo. METHODS: We evaluated the actin cytoskeletal structure and polymerization of CBX-treated LM8 cells using actin staining. Cell stiffness was measured using atomic force microscopy. Metastasis-related cell functions were analyzed using cell proliferation, wound healing, invasion, and cell adhesion assays. Furthermore, lung metastasis was examined in LM8-bearing mice administered with CBX. RESULTS: Treatment with CBX significantly increased actin staining intensity and stiffness of LM8 cells compared with vehicle-treated LM8 cells (p < 0.01). In Young's modulus images, compared with the control group, rigid fibrillate structures were observed in the CBX treatment group. CBX suppressed cell migration, invasion, and adhesion but not cell proliferation. The number of LM8 lung metastases were significantly reduced in the CBX administration group compared with the control group (p < 0.01). CONCLUSION: In this study, we demonstrated that CBX increases tumor cell stiffness and significantly reduces lung metastasis. Our study is the first to provide evidence that reducing cell motility by increasing cell stiffness might be effective as a novel anti-metastasis approach in vivo.

Combination of Everolimus and Bortezomib Inhibits the Growth and Metastasis of Bone and Soft Tissue Sarcomas via JNK/p38/ERK MAPK and AKT Pathways.

The combination of the mammalian target of rapamycin and proteasome inhibitors is a new treatment strategy for various tumors. Herein, we investigated the synergistic effect of everolimus and bortezomib on tumor growth and metastasis in bone and soft tissue sarcomas. The antitumor effects of everolimus and bortezomib were assessed in a human fibrosarcoma (FS) cell line (HT1080) and mouse osteosarcoma (OS) cell line (LM8) by MTS assays and Western blotting. The effects of everolimus and bortezomib on HT1080 and LM8 tumor growth in xenograft mouse models were evaluated using tumor volume and the number of metastatic nodes of the resected lungs. Immunohistochemistry was used to evaluate cleaved PARP expression. The combination therapy decreased FS and OS cell proliferation compared with either drug alone. This combination induced more intense p-p38, p-JNK, and p-ERK and activated apoptosis signals, such as caspase-3, compared with single-agent treatment. The combination treatment reduced p-AKT and MYC expression, decreased FS and OS tumor volumes, and suppressed lung metastases of OS. The combination therapy inhibited tumor growth in FS and OS and metastatic progression of OS via the JNK/p38/ERK MAPK and AKT pathways. These results could aid in the development of new therapeutic strategies for sarcomas.

Protocol for the 2ND-STEP study, Japan Clinical Oncology Group study JCOG1802: a randomized phase II trial of second-line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin and pazopanib.

BACKGROUND: Soft tissue sarcomas (STS) are a rare type of malignancy comprising a variety of histological diagnoses. Chemotherapy constitutes the standard treatment for advanced STS. Doxorubicin-based regimens, which include the administration of doxorubicin alone or in combination with ifosfamide or dacarbazine, are widely accepted as first-line chemotherapy for advanced STS. Trabectedin, eribulin, pazopanib, and gemcitabine plus docetaxel (GD), which is the empirical standard therapy in Japan, are major candidates for second-line chemotherapy for advanced STS, although clear evidence of the superiority of any one regimen is lacking. The Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group (JCOG) conducts this trial to select the most promising regimen among trabectedin, eribulin, and pazopanib for comparison with GD as the test arm regimen in a future phase III trial of second-line treatment for patients with advanced STS. METHODS: The JCOG1802 study is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m2 intravenously, every 3 weeks), eribulin (1.4 mg/m2 intravenously, days 1 and 8, every 3 weeks), and pazopanib (800 mg orally, every day) in patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. The principal eligibility criteria are patients aged 16 years or above; unresectable and/or metastatic STS; exacerbation within 6 months prior to registration; histopathological diagnosis of STS other than Ewing sarcoma, embryonal/alveolar rhabdomyosarcoma, well-differentiated liposarcoma and myxoid liposarcoma; prior doxorubicin-based chemotherapy for STS, and Eastern Cooperative Oncology Group performance status 0 to 2. The primary endpoint is progression-free survival, and the secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. The total planned sample size to correctly select the most promising regimen with a probability of > 80% is 120. Thirty-seven institutions in Japan will participate at the start of this trial. DISCUSSION: This is the first randomized trial to evaluate trabectedin, eribulin, and pazopanib as second-line therapies for advanced STS. We endeavor to perform a subsequent phase III trial comparing the best regimen selected by this study (JCOG1802) with GD. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials ( jRCTs031190152 ) on December 5, 2019.

New screw technique for posterior column and ischial fixation from the anterior approach for acetabular fractures.

Management of the ischial fragment in acetabular fractures is a considerable problem. In this report, we presented how to drill or screw around the posterior column and ischium from the anterior approach using a novel 'sleeve guide technique' and the difficulty of plating. A sleeve, drill, depth gauge and driver from DepuySynthes were prepared. The portal was about 2-3 cm inside the anterior superior iliac spine opposite to the side of the fracture. The sleeve was inserted to the screw point around quadrilateral area through the retroperitoneal space. Drilling, measuring screw length by a depth gauge and the screwing were performed through the sleeve. Case 1 used a one-third plate and case 2 used a reconstruction plate. With this technique, the approach angles to the posterior column and ischium were inclined, and plating and screw insertion could be performed with a low risk of organ injury.

The Characteristics of magnetic resonance imaging and immunohistochemical findings in de-differentiated liposarcoma.

PURPOSE: Radiological imaging in Dedifferentiated liposarcoma (DDLPS) often shows the coexistence of fatty and non-fatty solid components; however, it has been shown that when fatty components were not identified on magnetic resonance imaging (MRI), the diagnosis of DDLPS would not have been diagnosed if immunohistochemical (IHC) staining had not been performed. The aim of this study was to investigate the pattern of MRI and relationship between MRI and IHC findings in DDLPS. METHODS: We retrospectively reviewed the cases of 25 patients with DDLPS. To identify the MRI spectrum of DDLPS, tumors were classified into the following four categories based on MRI findings: I = a well-defined fatty mass and juxtaposed well-defined non-fatty mass, II = a non-fatty component within a predominantly fatty mass, III = a focal fatty component within a large non-fatty mass, and IV = a non-fatty mass with atypical MRI findings. IHC staining for CDK4, MDM2, and p16 were evaluated. RESULTS: Category IV tumor was the most common tumor in this population. Of the 22 patients who underwent IHC staining, MDM2, CDK4, and p16 were positive in 21, 20, and 19 patients, respectively. MDM2 was positive in all 11 patients with category IV tumors; CDK4 and p 16 were positive in 10 and eight patients, respectively. There was no difference of survival between the patients with category I, II and III and category IV. CONCLUSIONS: DDLPS without fatty components on MRI scans was mostly found. We recommend IHC staining to screen for DDLPS even if the tumors in STS cases have a non-fatty component.

Thin Cartilage Cap May Be Related to the Spontaneous Regression in Pediatric Patients with Osteochondroma.

BACKGROUND: The spontaneous regression of osteochondromas is rare, and only a few cases have been reported. Furthermore, the precise mechanism underlying spontaneous regression is unknown. This study aimed to examine the radiological findings of osteochondromas that had spontaneous regression and to identify potential indicators of this uncommon phenomenon in skeletally immature patients with osteochondromas. METHODS: We included 28 patients (15 males and 13 females) who met the eligibility criteria between 2002 and 2019. The mean age at initial diagnosis was 9.7 years old (2-16 years). The mean follow-up period was 6.4 years (3-16 years). RESULTS: Of the 28 patients, 10 (35.7%) had osteochondroma resolution. The osteochondroma resolved in one patient and regressed in nine. Tumor shrinkage is related to the thickness of the cartilage cap. The thickness of the cartilage cap did not correlate with age. CONCLUSIONS: Tumor shrinkage is associated with a thinner cartilage cap on magnetic resonance imaging. The thickness of the cartilage cap may be an important predictor of spontaneous regression in pediatric patients with osteochondroma.

Macrophages and vimentin in tissues adjacent to megaprostheses and mesh in reconstructive surgeries.

In reconstructive surgery using artificial materials after wide resection, soft tissues are usually adjacent to metal surfaces or mesh. The purpose of this study was to provide histological evaluation of the soft tissues adjacent to the metal surfaces of megaprostheses and mesh. Tissues from revision surgery of megaprosthesis and from wide resection after recurrent thoracic wall sarcoma were used. Histological analysis was evaluated by hematoxylin/eosin (HE) and Masson's trichrome staining, and by immunohistochemical staining for markers including cluster of differentiation 68 (CD68), vimentin, collagen type and S100A4. Soft tissue adherence to the smooth metal surface of Ti alloy was not observed. On the surface of capsule, CD68- and vimentin-positive cells formed a thin layer. In contrast, soft tissue adherence to a rough-surface cobalt chrome alloy was observed. Capsule was not apparent for this tissue, in which CD68- and vimentin-positive cells were aggregated randomly. In the resected tissues of recurrent chest wall sarcoma, muscles showed connections to connective soft tissues but did not invade to the inside of the mesh. Around the polypropylene mesh, large numbers of CD68- and vimentin-positive cells were seen. On the ePTFE, small numbers of CD68-positive cells were observed, while a larger number of the cells were vimentin positive. High accumulation of S100A4-positive cells was observed at the metal surface and polypropylene surface. Cells were strongly positive for CD68 and vimentin in tissues adjacent to metal and mesh surfaces. Macrophages and vimentin may play important roles in the foreign body reaction to metal and mesh, and so may contribute to encapsulation and fibrosis.

Is Lymphocyte C-Reactive Protein Ratio Useful for Predicting Survival in Patients with Non-Metastatic Soft Tissue Sarcoma?

Background: Recently, the lymphocyte-to-CRP ratio (LCR) was found to have a prognostic role in many cancers. However, the clinical significance of LCR in patients with soft tissue sarcoma (STS) has not yet been established. This study aimed to determine whether LCR can predict disease-specific survival (DSS) and event-free survival (EFS) in patients with STS. Methods: In this study, 132 patients were enrolled. The mean follow-up periods were 76.5 months. Blood examinations were performed prior to treatment for all patients. Results: The 5-year DSS in patients with higher and lower LCR was 86.5% and 52.8%, respectively (p < 0.001). Patients with lower LCR had worse survival than those with higher LCR. The 5-year EFS in patients with higher and lower LCR was 66.2% and 31.2%, respectively (p < 0.001). On Receiver operating characteristic analysis, however, there was no significant difference in the area under curve (AUC) between CRP level (AUC = 0.72) and LCR (AUC = 0.711). Conclusions: LCR may be a prognostic factor for predicting oncological events in multivariate analysis, although ROC analysis could not show the superiority of LCR to CRP for predicting oncological outcomes in patients with STS.

Radiodynamic therapy with acridine orange local administration as a new treatment option for primary and secondary bone tumours.

AIMS: Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. METHODS: We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 µg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. RESULTS: The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 µg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. CONCLUSION: AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo.Cite this article: Bone Joint Res 2022;11(10):685-692.