Revision surgery for periprosthetic fracture of distal femur after endoprosthetic replacement of knee joint following resection of osteosarcoma.

Purpose: Periprosthetic fracture (PPF) is one of the severe complications in patients with osteosarcoma and carries the risk of limb loss. This study describes the characteristics, treatment strategies, and outcomes of this complication. Methods: Patients were consecutively included who were treated at our institution between 2016 and 2020 with a PPF of distal femur. The treatment strategies included two types: 1) open reduction and internal fixation with plates and screws and 2) replacement with long-stem endoprosthesis and reinforcement with wire rope if necessary. Results: A total of 11 patients (mean age 12.2 years (9-14)) were included, and the mean follow-up period was 36.5 (21-54) months. Most fractures were caused by direct or indirect trauma (n = 8), and others (n = 3) underwent PPF without obvious cause. The first type of treatment was performed on four patients, and the second type was performed on seven patients. The mean Musculoskeletal Tumor Society (MSTS) score was 20 (17-23). All patients recovered from the complication, and limb preservation could be achieved. Conclusion: PPF is a big challenge for musculoskeletal oncologists, particularly in younger patients. Additionally, PPF poses a challenge for orthopedic surgeons, as limb preservation should be an important goal. Hence, internal fixation with plates and endoprosthetic replacement are optional treatment strategies based on fracture type and patient needs.

Association of circulating tumor cells and IMP3 expression with metastasis of osteosarcoma.

Background: Circulating tumor cells (CTCs) have been identified as a prognostic biomarker of tumors such as breast cancer and nasopharyngeal carcinoma, because they are obtained through a simple and noninvasive blood draw or liquid biopsy, but its clinical significance in osteosarcoma is still unclear. In this study, we analyzed the relationship between CTCs and clinicopathological features and discussed whether CTCs could be used as a biomarker for metastasis in osteosarcoma. Methods: We enrolled 50 osteosarcoma patients with Enneking Stage IIB and Stage III and detected CTCs in 5 ml of peripheral blood samples collected from patients using the Canpatrol® CTC detection platform. Subsequently, multiplex RNA in situ hybridization (RNA-ISH) based on various molecular markers was performed to identify and classify CTCs. The relationships between clinical pathological features and CTC counts, subtypes (epithelial type, E type; hybrid epithelial/mesenchymal type, H type; mesenchymal type, M type), and insulin-like growth factor mRNA-binding protein 3 (IMP3) expression in CTCs were analyzed. Results: CTCs were detected in 86% (43/50) of the osteosarcoma patients. The CTC counts, especially the total CTCs and H-type CTCs, signifcantly differed between Enneking Stage IIB and Stage III patients (P < 0.05). No significant differences were observed between the CTC count or type and other clinicopathological features (P > 0.05). There were significant differences in the expression of IMP3 in different types of CTCs, and the IMP3 positive rates in E/H/M type CTCs were 38.4, 65.6, and 62.0%, respectively (P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that IMP3-positive CTC count had the best performance for diagnostic metastasis, with the largest area under the curve of 0.873 and cutoff value of four cells/5ml blood (sensitivity = 87.5%; specificity = 82.4%). Serial CTC monitoring in one patient suggested that total CTCs and H-type CTCs were associated with disease progression. Conclusion: This study demonstrates that the CTCs, especially the IMP3-positive CTCs and H/M-type CTCs, are related to the metastasis of osteosarcoma.

HMGB1 Positive Feedback Loop Between Cancer Cells and Tumor-Associated Macrophages Promotes Osteosarcoma Migration and Invasion.

Numerous studies have demonstrated the key roles of tumor-associated macrophages (TAMs) in osteosarcoma metastasis. Higher levels of high mobility group box 1 (HMGB1) promote osteosarcoma progression. However, whether HMGB1 is involved in the polarization of M2 macrophages into M1 macrophages in osteosarcoma remains largely unknown. Here, HMGB1 and CD206 mRNA expression levels were measured by a quantitative reverse transcription-polymerase chain reaction in osteosarcoma tissues and cells. HMGB1 and receptor for advanced glycation end products (RAGE) protein expression levels were measured by western blotting. Osteosarcoma migration was measured using transwell and wound-healing assays, while a transwell assay determined osteosarcoma invasion. Macrophage subtypes were detected using flow cytometry. HMGB1 expression levels were aberrantly enhanced in osteosarcoma tissues compared with normal tissues and were positively correlated with AJCC III and IV stages, lymph node metastasis, and distant metastasis. Silencing HMGB1 inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells. Furthermore, reduced HMGB1 expression levels in conditioned media derived from osteosarcoma cells induced the polarization of M2 TAMs to M1 TAMs. In addition, silencing HMGB1 inhibited the liver and lung metastasis of tumors and reduced the expression levels of HMGB1, CD163, and CD206 in vivo. HMGB1 was found to regulate macrophage polarization through RAGE. Polarized M2 macrophages induced osteosarcoma migration and invasion, activating HMGB1 expression in osteosarcoma cells to form a positive feedback loop. In conclusion, HMGB1 and M2 macrophages enhanced osteosarcoma migration, invasion, and EMT through positive feedback regulation. These findings reveal the significance of tumor cell and TAM interactions in the metastatic microenvironment.

En bloc resection of huge primary tumors with epidural involvement in the mobile spine using the "rotation-reversion" technique: Feasibility, safety, and clinical outcome of 11 cases.

Background: En bloc resection of spinal tumors provides better local control and survival outcomes than intralesional resection. Safe margins during en bloc resection of primary spinal tumors with epidural involvement are required for improved outcomes. The present study describes a "rotation-reversion" technique that has been used for en bloc resection of huge primary tumors in the mobile spine with epidural involvement and reported the clinical outcomes in these patients. Methods: All patients with primary spinal tumors who were treated with the rotation-reversion technique at our institution between 2015 and 2021 were evaluated retrospectively. Of the patients identified, those with both huge extraosseous soft-tissue masses and epidural involvement were selected for a case review. Clinical and radiological characteristics, pathologic findings, operative procedures, complications, and oncological and functional outcomes of these patients were reviewed. Results: Of the 86 patients identified with primary spinal tumors who underwent en bloc resection using the rotation-reversion technique between 2015 and 2021, 11 had huge extraosseous soft-tissue masses with epidural involvement in the mobile spine. The average maximum size of these 11 tumors was 8.1 × 7.5 × 9.7 cm. Median follow-up time was 28.1 months, mean operation time was 849.1 min (range 465-1,340 min), and mean blood loss was 6,972.7 ml (range 2,500-17,700 ml), with 10 (91%) of the 11 patients experiencing perioperative complications. The negative margin rate was 91%, with only one patient (9%) experiencing local recurrence. Ten patients were able to walk normally or with a crutch at the last follow-up, whereas one was completely paralyzed preoperatively. Conclusion: The rotation-reversion technique is an effective procedure for the en bloc resection of huge primary spinal tumors, with the extension of invasion in selected patients including not only the vertebral body but also the pedicle and part of the posterior arch.

Image-guided percutaneous biopsy and pathological diagnosis in atypical tuberculous spondylitis: a case series and clinical outcomes.

Background: Tuberculous spondylitis can be difficult to distinguish from alternative spinal pathologies such as malignancy, particularly if the imaging features are not typical. Biopsy and histopathological analysis are facilitative to the early and accurate diagnosis of atypical tuberculous spondylitis and the clinical management. The purpose of this study is to describe some of the atypical imaging features of tuberculous spondylitis diagnosed by image-guided percutaneous biopsy, as well as associated treatment outcomes. Methods: We performed a retrospective analysis of all patients diagnosed with tuberculous spondylitis after image-guided percutaneous biopsy at The Third Affiliated Hospital of Southern Medical University between 2013 and 2020. Of the patients identified, those with atypical imaging features were selected for case review. All patients were given anti-tuberculous medication treatment with or without surgery. The imaging features, histological and microbiological results, and clinical presentations and outcomes were evaluated. Neurological function was evaluated according to the Frankel grading system. The clinical outcomes were evaluated by Visual Analogic Scale (VAS) scores for pain, imaging [X-ray, computed tomography (CT), and magnetic resonance imaging (MRI)] results, and laboratory examinations. Comparison of VAS scores was made by Student t-test. Results: Of the 102 patients identified with tuberculous spondylitis between 2013 and 2020, eight patients (two females and six males) with a mean age of 41.6 years (range, 18-61 years) demonstrated atypical imaging findings, including central vertebral body lesion, multiple skip vertebral lesions, extradural mass lesion and anterior subperiosteal lesion. All eight patients received anti-tuberculous medication treatment, and six underwent surgery. One patient developed a pleural effusion after debridement of the thoracic lesion. The mean follow-up period was 16.2 months (6-37 months). The VAS scores before treatment and at the final follow-up showed significant differences (7.25±1.49 and 0.0±0.0, respectively, P<0.01). Improved neurological function were observed in all patients. Solid fusion and osteogenic osteosclerosis were observed at the final follow-up, and no recurrence was observed in any cases. Conclusions: All eight patients had a good prognosis. Image-guided biopsy and histopathological analysis are helpful for the early diagnosis of tuberculous spondylitis, especially when imaging features are not typical for this condition.

mGluR5 promotes the progression of multiple myeloma in vitro via Ras-MAPK signaling pathway.

BACKGROUND: Multiple myeloma (MM) is a malignant plasma cancer which remains difficult to be cured. Recently, numerous research studies have appeared, exploring MM from molecular level. However, there is no study about the impact of metabotropic glutamate receptors (mGluRs), especially mGluR5, on MM progression. Thus, the present research was dedicated to the exploration of the influence of mGluR5 on MM. OBJECTIVES: In this research, we used quantitative real-time polymerase chain reaction (qRT-PCR) to check the gene expression in MM, western blot assay to check the protein expression of the gene, MTT assay to quantify the cell viability, and flow cytometry (FCM) apoptosis method to evaluate cell apoptosis in order to acquire the results. The purpose was to assess the role of mGluR5 in MM cells. MATERIAL AND METHODS: The qRT-PCR was used and it was found that mGluR5 was overexpressed in MM cell lines and MM tissues compared to normal ones. To better observe the function of mGluR5 in MM, cell viability and apoptosis were checked using MTT and FCM apoptosis assays after the treatment with agonists and antagonists. RESULTS: Agonist-induced mGluR5 upregulation could promote MM cell viability and inhibit apoptosis. The same results were obtained through MTT and FCM apoptosis assays after upregulation and downregulation of mGluR5 by transfection. To further investigate the inner mechanism, the effect of mGluR5 on Ras-MAPK pathway was checked using western blot. It was found that the upregulation of mGluR5 could activate the Ras-MAPK pathway. CONCLUSIONS: The mGluR5 might be involved in promoting cell proliferation and inhibiting cell apoptosis in MM. It can be an essential biomarker in the screening for MM and a potential part of future MM therapies.

Application of a novel porous tantalum implant in rabbit anterior lumbar spine fusion model: in vitro and in vivo experiments.

BACKGROUND: Some porous materials have been developed to enhance biologic fusion of the implants to bone in spine fusion surgeries. However, there are several inherent limitations. In this study, a novel biomedical porous tantalum was applied to in vitro and in vivo experiments to test its biocompatibility and osteocompatibility. METHODS: Bone marrow-derived mesenchymal stem cells (BMSCs) were cultured on porous tantalum implant. Scanning electron microscope (SEM) and Cell Counting Kit-8 assay were used to evaluate the cell toxicity and biocompatibility. Twenty-four rabbits were performed discectomy only (control group), discectomy with autologous bone implanted (autograft group), and discectomy with porous tantalum implanted (tantalum group) at 3 levels: L3-L4, L4-L5, and L5-L6 in random order. All the 24 rabbits were randomly sacrificed at the different post-operative times (2, 4, 6, and 12 months; n = 6 at each time point). Histologic examination and micro-computed tomography scans were done to evaluate the fusion process. Comparison of fusion index scores between groups was analyzed using one-way analysis of variance. Other comparisons of numerical variables between groups were made by Student t test. RESULTS: All rabbits survived and recovered without any symptoms of nerve injury. Radiographic fusion index scores at 12 months post-operatively between autograft and tantalum groups showed no significant difference (2.89 ±â€Š0.32 vs. 2.83 ±â€Š0.38, F = 244.60, P = 0.709). Cell Counting Kit-8 assay showed no significant difference of absorbance values between the leaching liquor group and control group (1.25 ±â€Š0.06 vs. 1.23 ±â€Š0.04, t = -0.644, P = 0.545), which indicated the BMSC proliferation without toxicity. SEM images showed that these cells had irregular shapes with long spindles adhered to the surface of tantalum implant. No implant degradation, wear debris, or osteolysis was observed. Histologic results showed solid fusion in the porous tantalum and autologous bone implanted intervertebral spaces. CONCLUSION: This novel porous tantalum implant showed a good biocompatibility and osteocompatibility, which could be a valid biomaterial for interbody fusion cages.

[Minimally invasive treatment of Gartland type III humerus supracondylar fracture in children].

OBJECTIVE: To explore minimally invasive surgical techniques for Gartland type III humeral supracondylar fracture in children and evaluate the outcomes of the patients. METHODS: We retrospectively analyzed 62 children (43 boys and 19 girls, aged 1 year and 8 months to 13 years and 2 months, mean 6 years and 3 months) with Gartland type III humeral supracondylar fracture treated in our department from July, 2011 to September, 2013, including 42 with extension-ulnar type humeral supracondylar fracture and 20 with deviation-ulnar type. The injury to operation time ranged from 6 to 48 h with a mean of 13.5 h. Close reduction and percutaneous pinning internal fixation was performed by a single surgeon in all cases with plaster cast fixation for 3 to 4 weeks. The patients were followed up regularly and Flynn elbow scoring criteria was used to evaluate the outcomes. RESULTS: The mean operation time was 26.8 ± 15.6 min with a mean intraoperative fluoroscopy frequency of 9.2 ± 2.6 and a mean follow-up for 16.5 months (6 to 30 months). Clinical healing was achieved in 3 to 4 weeks without fracture displacement after removal of the internal fixation, and active and passive functional exercise was initiated. According to the Flynn elbow scoring criteria, excellent outcome was achieved in 53 (85%) cases at 3 months in 62 (100%) cases at 6 months after the surgery. No such complications as osteofascial compartment syndrome or vascular injuries occurred in these patients. Three children had alnar nerve injury symptoms after the operation but all recovered in 3 months. CONCLUSION: The minimally invasive method with closed reduction and percutaneous pinning internal fixation is feasible for treatment of Gartland type III humerus condyle fracture in children. This approach involves relatively simple operation with shorter operation time, minimal trauma, and less complications after operation, and promotes early functional recovery of the elbow joint.