Activating α7nAChR helps post-myocardial infarction healing by regulating macrophage polarization via the STAT3 signaling pathway.

BACKGROUND: Monocytes/macrophages play critical roles in inflammation and cardiac remodeling following myocardial infarction (MI). The cholinergic anti-inflammatory pathway (CAP) modulates local and systemic inflammatory responses by activating α7 nicotinic acetylcholine receptors (α7nAChR) in monocytes/macrophages. We investigated the effect of α7nAChR on MI-induced monocyte/macrophage recruitment and polarization and its contribution to cardiac remodeling and dysfunction. METHODS: Adult male Sprague Dawley rats underwent coronary ligation and were intraperitoneally injected with the α7nAChR-selective agonist PNU282987 or the antagonist methyllycaconitine (MLA). RAW264.7 cells were stimulated with lipopolysaccharide (LPS) + interferon-gamma (IFN-γ) and treated with PNU282987, MLA, and S3I-201 (a STAT3 inhibitor). Cardiac function was evaluated by echocardiography. Masson's trichrome and immunofluorescence were used to detect cardiac fibrosis, myocardial capillary density, and M1/M2 macrophages. Western blotting was used to detect protein expression, and the proportion of monocytes was measured using flow cytometry. RESULTS: Activating the CAP with PNU282987 significantly improved cardiac function and reduced cardiac fibrosis and 28-day mortality after MI. On days 3 and 7 post-MI, PNU282987 reduced the percentage of peripheral CD172a + CD43low monocytes and the infiltration of M1 macrophages in the infarcted hearts, whereas it increased the recruitment of peripheral CD172a + CD43high monocytes and M2 macrophages. Conversely, MLA exerted the opposite effects. In vitro, PNU282987 inhibited M1 macrophage polarization and promoted M2 macrophage polarization in LPS + IFN-γ-stimulated RAW264.7 cells. These PNU282987-induced changes in LPS + IFN-γ-stimulated RAW264.7 cells were reversed by administering S3I-201. CONCLUSION: Activating α7nAChR inhibits the early recruitment of pro-inflammatory monocytes/macrophages during MI and improves cardiac function and remodeling. Our findings suggest a promising therapeutic target for regulating monocyte/macrophage phenotypes and promoting healing after MI.

Two cases of spindle cell tumors with S100 and CD34 co-expression showing novel RAF1 fusions.

BACKGROUND: Recently, a novel group of CD34 and S100 co-expression spindle cell tumors with distinctive stromal and perivascular hyalinization harboring recurrent gene fusions involving RET, RAF1, BRAF, and NTRK1/2 gene has been identified. CASE PRESENTATION: In this study, we reported two Chinese male patients with soft tissue tumors presenting in the right knee joint and the left thigh, respectively. For both patients, the tumors were completely excised with clear margin. Microscopically, case 1showed morphological overlap with neurofibroma, and case 2 showed overlap with lipomatous solitary fibrous tumor. Both tumors showed co-expression of S100 and CD34, and absence of SOX10. Genomic profiling with DNA-based next-generation sequencing (NGS) assay was performed and revealed KIF5B-RAF1 (K16:R8) and TLN2-RAF1 (T54:R8) rearrangements. RNA-based NGS and RT-PCR were performed to confirm the gene fusion. CONCLUSIONS: Though systemic therapy was not indicated in these two patients, identification of targetable kinase fusions may help to refine tumors with an ambiguous immunoprofile, and provides suggestions for targeted therapy in rare aggressive cases.

Phase I study of pegylated liposomal doxorubicin and cisplatin in patients with advanced osteosarcoma.

PURPOSE: The repeated use of doxorubicin is limited due to dose-limiting cardiac toxicity. Pegylated liposomal doxorubicin (PEG-LD, Duomeisu) has a reduced cardiac toxicity. This phase I study aimed to investigate the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of the PEG-LD and cisplatin combination in patients with metastatic and recurrent osteosarcoma. METHODS: Patients were given PEG-LD at a dose of 40, 50, or 60 mg/m2 on day 1 of each 21-day cycle, according to a 3 + 3 approach for dose escalation. Cisplatin was administered as a fixed dose of 100 mg/m2 for every cycle. Toxicities and tumor response were observed. RESULTS: A total of 15 patients were enrolled in this trial, and nine of the patients had received prior doxorubicin. The MTD of PEG-LD was reached at 50 mg/m2 in this regimen, with neutropenic fever and stomatitis as DTLs. The main adverse event (AE) was myelosuppression. The most common non-hematological AEs were vomiting, hypoproteinemia, stomatitis and transient sinus arrhythmia. Grade 3-4 toxicity was neutropenia, leukopenia, thrombocytopenia, anemia and stomatitis in the whole cohort. All the AEs were relieved after symptomatic and supportive treatment. Totally, the overall response rate was 13.3% and disease control rate was 66.7%. For the six patients who have not received prior doxorubicin, one partial response and five stable diseases were observed. CONCLUSION: We provide the data showing that PEG-LD 50 mg/m2 combined with cisplatin 100 mg/m2 demonstrated an acceptable safety profile and promising clinical activity in advanced osteosarcoma, which merits further evaluation in phase II studies. TRIAL REGISTRATION: ChiCTR1900021550.

Computer navigation-aided joint-preserving resection and custom-made endoprosthesis reconstruction for bone sarcomas: long-term outcomes.

BACKGROUND: Computed tomography (CT) and magnetic resonance imaging (MRI) data can be fused to identify the tumor boundaries. This enables surgeons to set close but tumor-free surgical margins and excise the tumor more precisely. This study aimed to report our experience in performing computer navigation-aided joint-preserving resection and custom-made endoprosthesis reconstruction to treat bone sarcoma in the diaphysis and metaphysis of the femur and tibia. METHODS: Between September 2008 and December 2015, 24 patients with bone sarcomas underwent surgical resection and joint-sparing reconstruction under image-guided computer navigation. The cohort comprised 16 males and eight females with a median age of 19.5 years (range: 12-48 years). The tumor location was the femoral diaphysis in three patients, distal femur in 19, and proximal tibia in two. The tumors were osteosarcoma (n = 15), chondrosarcoma (n = 3), Ewing sarcoma (n = 3), and other sarcomas (n = 3). We created a pre-operative plan for each patient using navigation system software and performed navigation-aided resection before reconstructing the defect with a custom-made prosthesis with extracortical plate fixation. RESULTS: Pathological examination verified that all resected specimens had appropriate surgical margins. The median distance from the tumor resection margin to the joint was 30 mm (range: 13-80 mm). The median follow-up duration was 62.5 months (range: 24-134 months). Of the 24 patients, 21 remain disease free, one is alive with disease, and two died of the disease. One patient developed local recurrence. Complications requiring additional surgical procedures occurred in six patients, including one with wound hematoma, one with delayed wound healing, one with superficial infection, one with deep infection, and two with mechanical failure of the prosthesis. The mean Musculoskeletal Tumor Society score at the final follow-up was 91% (range: 80%-100%). The 5- and 10-year implant survival rates were 91.3% and 79.9%, respectively. CONCLUSIONS: Computer navigation-aided joint-preserving resection and custom-made endoprosthesis reconstruction with extracortical plate fixation is a reliable surgical treatment option for bone sarcoma in the diaphysis and metaphysis of the femur and tibia.

[Result analysis of percutaneous core needle biopsy for bone tumors in upper limbs with pathological fracture].

OBJECTIVE: To analyze the results of percutaneous core needle biopsy for bone tumors in upper limbs with pathologic fracture and to find the possible factors that could impact the results. METHODS: The including criteria for this study was the patients who had received percutaneous core needle biopsy and definitive surgery, whose tumor was located at upper limb with pathologic fracture. From January 2015 to December 2019, seventy-seven patients were enrolled. There were 55 males and 22 females. The median age was 27 years old (range:5 to 88 years old). The tumor located at humerus in 67 cases, radius in 8 cases and ulna in 2 cases. If the pathologic diagnosis of core needle biopsy was the same with the definitive surgery, it was defined as "correct". If the pathologic diagnosis of biopsy for benign or malignant was right but the exact diagnostic name was not the same with definitive surgery, it was defined as "supportive". If the pathologic diagnosis of biopsy for benign or malignant was not correct, it was defined as "wrong". We retrospectively analyzed the accuracy and impact factors for core needle biopsy. RESULTS: The result was "correct" in 63 cases(81.8%), "supportive" in 14 cases(18.2%), and "wrong" in 0 cases. We analyzed the gender, age, location, fracture displacement, the destroyed type for bone tumor, soft tissue mass, fluid area in the tumor as the factors. The results showed the rate for "correct" was significantly higher when the tumor had soft tissue mass (P< 0.05) and lower when the fluid area existed inside the tumor (P<0.05). CONCLUSION: The accuracy of percutaneous core needle biopsy for upper limb bone tumor with pathologic is high and acceptable. The biopsy chosen the soft tissue mass area can increase the accuracy.

Frequent amplification of HDAC genes and efficacy of HDAC inhibitor chidamide and PD-1 blockade combination in soft tissue sarcoma.

BACKGROUND: The advent of immune checkpoint therapy has been a tremendous advance in cancer treatment. However, the responses are still insufficient in patients with soft tissue sarcoma (STS). We aimed to identify rational combinations to increase the response to immune checkpoint therapy and improve survival. METHODS: Whole-exome sequencing (WES) was performed in 11 patients with liposarcoma. Somatic copy number alterations (SCNAs) were analyzed at the gene level to identify obvious amplification patterns in drug-target genes. The expression and prognostic value of class I histone deacetylases (HDACs) was evaluated in 49 patients with sarcoma in our center and confirmed in 263 sarcoma samples from The Tumor Cancer Genome Atlas (TCGA) database. Q-PCR, flow cytometry and RNA-seq were performed to determine the correlations between class I HDACs, chidamide and PD-L1 in vitro and in vivo. The efficacy of combining chidamide with PD-1 blockade was explored in an immunocompetent murine model and a small cohort of patients with advanced sarcoma. Western blot, ChIP assay and dual luciferase assessment were applied in the mechanistic study. RESULTS: The HDAC gene family was frequently amplified in STS. SCNAs in the HDAC gene family were extensively amplified in 8 of 11 (73%) patients with liposarcoma, based on a drug-target gene set, and we verified amplification in 76.65% (197/257) of cases by analyzing TCGA sarcoma cohort. Class I HDAC expression is associated with a poor prognosis for patients with STS, and its inhibition is responsible for promoting apoptosis and upregulating of programmed cell death ligand 1 (PD-L1). The HDAC class I inhibitor chidamide significantly increases PD-L1 expression, increased the infiltration of CD8+ T cells and reduced the number of MDSCs in the tumor microenvironment. The combination of chidamide with an anti-PD-1 antibody significantly promotes tumor regression and improves survival in a murine model. Moreover, chidamide combined with the anti-PD-1 antibody toripalimab is effective in patients with advanced and metastatic sarcoma, and the side effects are tolerable. Mechanistically, chidamide increases histone acetylation at the PD-L1 gene through the activation of the transcriptional factor STAT1. CONCLUSIONS: The combination of chidamide and anti-programmed cell death 1 (PD-1) therapy represents a potentially important strategy for STS.

Feasibility of MRI Radiomics for Predicting KRAS Mutation in Rectal Cancer.

The mutation status of KRAS is a significant biomarker in the prognosis of rectal cancer. This study investigated the feasibility of MRI-based radiomics in predicting the mutation status of KRAS with a composite index which could be an important criterion for KRAS mutation in clinical practice. In this retrospective study, a total of 127 patients with rectal cancer were enrolled. The 3D Slicer was used to extract the radiomics features from the MRI images, and sparse support vector machine (SVM) with linear kernel was applied for feature reduction. The radiomics classifier for predicting the KRAS status was then constructed by Linear Discriminant Analysis (LDA) and its performance was evaluated. The composite index was determined with LDA model. Out of 127 rectal cancer subjects, there were 44 KRAS mutation cases and 83 wild cases. A total of 104 radiomics features were extracted, 54 features were filtered by linear SVM with L1-norm regularization and 6 features that had no significant correlations within them were finally selected. The radiomics classifier constructed using the 6 features featured an AUC value of 0.669 (specificity: 0.506; sensitivity: 0.773) with LDA. Furthermore, the composite index (Radscore) had statistically significant difference between the KRAS mutation and wild groups. It is suggested that the MRI-based radiomics has the potential in predicting the KRAS status in patients with rectal cancer, which may enhance the diagnostic value of MRI in rectal cancer.

Comparative Analysis of Early Follow-up of Biologic Fixation and Cemented Stem Fixation for Femoral Tumor Prosthesis.

OBJECTIVE: To compare the safety and efficacy between biologic fixation and traditional cement stems for the fixation of distal femoral prostheses for reconstruction following tumor resection. METHODS: Retrospective analysis was performed of patients who received a first distal femoral tumor prosthesis, with a rotating hinge, in the Department of Orthopaedic Oncology of Beijing Jishuitan Hospital between October 2011 and January 2016. Two hundred and sixty eligible cases were enrolled, with a cemented fixation used in 199 of these cases and a biologic fixation in 61 cases. Survival rates and survival time of prostheses were analyzed, with prosthetic failure considered as the endpoint event for survival time of the prosthesis. Kaplan-Meier survival curve and the log-rank test were used to compare survival rates between the two types of fixation methods, and factors that may affect the survival rate of prosthesis were evaluated. RESULTS: Of the 260 cases forming our study group, 138 were males and 122 females, with 102 males and 97 females in the cemented fixation group (mean age, 25.8 years; range, 8-72 years) and 36 males and 25 females in the biologic fixation group (mean age, 25.5 years; range, 12-59 years). Osteosarcoma was the most common type of tumor (188 cases, 72.3%), of which 145 cases (72.9%) were in the cemented and 45 cases (72.1%) in the biologic fixation group. Among the 260 cases enrolled into the study group, 13 patients were lost to follow-up. The average duration of follow-up for the remaining 247 cases was 28.8 months (median, 28.8 months; range, 4-61 months). The 3-year overall survival rate of prostheses was 87.2% for the biologic fixation group and 80.4% in the cemented fixation group (P = 0.389). The 3-year mechanical survival rate (excluding cases of infection and oncologic progression) was 100% for the biologic fixation and 97.6% for the cemented fixation group (P = 0.468). Complications were identified in 21 cases: 3 cases (5%) in the biologic and 18 cases (9.6%) in the cemented fixation group (P = 0.264). Two revisions were required in the cemented fixation group, but no revision was required in the biologic fixation group. A total of 10 patients required amputation after prosthesis implantation. Of these, 7 cases (4 cement and 3 biologic) were due to tumor recurrence; 3 cases were due to infection, with all cases occurring in the cement fixation group. CONCLUSION: The current study provides a baseline reference for future mid-term to long-term follow-up, laying the foundation for further studies and comparison of the incidence of aseptic loosening of both types of prosthesis.

Elevated Circulating Fibrocytes Is a Marker of Left Atrial Fibrosis and Recurrence of Persistent Atrial Fibrillation.

BACKGROUND: In atrial fibrillation (AF), a more extensively fibrotic left atrium (LA) provides a substrate for arrhythmias and increases risk of relapse following ablation. Fibrocytes are bone marrow-derived circulating mesenchymal progenitors that have been identified in the atrium of patients with AF who have valvular diseases. The present study investigates the associations between circulating fibrocytes and LA fibrosis or the prevalence of recurrence after ablation in patients with persistent AF. METHODS AND RESULTS: We measured the proportion, differentiation, and migration of circulating fibrocytes from patients with persistent AF (n=40), those with paroxysmal AF (n=30), and sinus rhythm controls (n=30). LA low-voltage (fibrosis) area was identified by an electroanatomic mapping system, and patients were followed up for 1 year after ablation. The relationship between circulating fibrocyte percentage and LA low-voltage area or recurrence was assessed by multivariate regression analysis. Circulating fibrocyte percentage positively associated with LA low-voltage area in the persistent AF group, and circulating fibrocyte (≥4.05%) was a significant predictor of 1-year recurrence after ablation. Cultured fibrocytes exhibited enhanced potential of differentiation in the persistent AF group (67.58±1.54%) versus the paroxysmal AF group (56.67±1.52%) and sinus rhythm controls (48.43±1.79%). Furthermore, expression of fibroblast activation markers and cell migratory ability were also elevated in differentiated fibrocytes from patients with persistent AF. Transforming growth factor ß1 and stromal cell-derived factor 1 were elevated in the plasma of patients with persistent AF and were shown to promote fibrocyte differentiation and migration, respectively. CONCLUSIONS: In patients with persistent AF, increased circulating fibrocytes served as a marker of LA fibrosis and recurrence.

Magnetic Resonance Imaging for the Assessment of Long Bone Tumors.

BACKGROUND: Wide resection margins of osseous tumors are associated with a low incidence of local recurrence, making accurate measurement of the intraosseous extent of primary malignant long bone tumors is crucial. We compared the intraosseous tumor extent assessed by magnetic resonance imaging (MRI) with the gross specimen to evaluate the accuracy of MRI. METHODS: A total of 255 patients with primary malignant tumors in the long bones were included. Using MRI, we defined the length of tumor as the distance from the articular surface to the boundary between abnormal and normal marrow signal. The extent of the abnormal intraosseous signal was measured on unenhanced T1-weighted (T1WI) magnetic resonance images after chemotherapy. All gross surgical specimens were sectioned, and tumor extent was measured. Wilcoxon signed-rank test was used to test the differences between MRI and gross specimen findings. Spearman's correlation analysis was used to test the correlation between groups. RESULTS: Median tumor length by gross specimen (112 mm; range, 45-300 mm) was longer than that by MRI (108 mm; range, 45-304 mm; Z = -6.916, P < 0.001). Of 255 images, tumor length was accurately represented on 27 T1WI magnetic resonance images, overestimated on 79 images, and underestimated on 149 images. The median difference between imaging and gross specimen measurements was 2.0 mm (range: 1.0-15.0 mm) for the 79 cases where tumor length was overestimated, and 5.0 mm (range: 1.0-18.0 mm) for the 149 cases where tumor length was underestimated. The Spearman correlation demonstrated a high correlation of tumor length on gross specimen with the tumor length on MRI (R = 0.99, P < 0.01). CONCLUSIONS: We conclude that preoperative MRI could be a useful method in determining intramedullary malignant bone tumor boundaries and may serve as an accepted assessment method of long bone tumors before limb-sparing surgery.

Transition from Tumor Tissue to Bone Marrow in Patients with Appendicular Osteosarcoma after Neoadjuvant Chemotherapy.

BACKGROUND:: Limb-salvage surgery is the standard procedure for the treatment of appendicular osteosarcoma. Precise resection is the trend in limb-salvage surgery. The aim of this study was to evaluate a large series of cases to identify the histological relationship between the tumor and marrow and determine the intramedullary transition type and width from the tumor to normal marrow in patients with osteosarcoma after neoadjuvant chemotherapy. METHODS:: One hundred and six osteosarcoma specimens were evaluated. The tissue specimens were sectioned through the coronal axis by an electronic saw. The tissue was immersed in formalin solution for fixation and subsequently decalcified. The interface between the tumor and normal bone marrow was grossly determined and submitted for microscopic evaluation to detect the relationship between the tumor and bone marrow and identify the transition type and width. All histological slides were examined by experienced orthopedic pathologists. RESULTS:: Histologically, the interface between the tumor and normal bone marrow was classified into two patterns: "clear" and "infiltrated." The clear pattern, characterized by a clear boundary between the tumor and marrow, was identified in sixty cases (56.6%). A subtype of the clear type, characterized by fibrous bands between the tumor and marrow, was found in 13 cases (12.3%). The infiltrated pattern, characterized by a boundary with tumor cell clusters embedded in the marrow, was found in 46 cases (43.4%). The infiltrating depth varied from 1 to 4 mm (mean, 2.6 ± 0.7 mm). No tumor cells were observed in the normal bone marrow areas next to the interface. CONCLUSIONS:: The transition from osteosarcoma tissue to bone marrow after neoadjuvant chemotherapy can be divided into two histological patterns: clear and infiltrated. The greatest infiltration width was 4 mm from tumor to normal marrow in this study. This depth should be considered in the presurgical plan.

Treatment and outcomes of tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors: retrospective review of 12 patients.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia. Nonspecific symptoms make the diagnosis elusive. In addition, locating the responsible tumor(s) is challenging. The aim of this study was to investigate the clinical management and outcomes of TIO. METHODS: The clinical features, diagnostic procedures, treatment, and outcomes of 12 patients were reviewed retrospectively. RESULTS: The cohort comprised six men and six women (mean age 45.5 ± 9.9 years, range 23-61 years). The mean duration of disease was 3.7 ± 2.6 years. All patients manifested progressive bone pain, muscle weakness, and/or difficulty walking. Serum phosphorus concentrations were low in all patients (mean 0.42 ± 0.12 mmol/L). Technetium-99m octreotide scintigraphy was performed in 11 patients and showed lesions in the right distal femur, left femoral head, and right tibial plateau, respectively, in three patients. Magnetic resonance imaging (MRI) was negative for lesions in one patient. Two patients underwent biopsies that showed negative histopathology. Two patients, at 2 years and 8 months, respectively, after having negative technetium-99m octreotide studies, underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT), which revealed lesions in the sacrum and soft tissue of the left palm, respectively. One tumor was detected by CT and MRI. Overall, lesion sites were the head (two patients, 16.7%), thoracic and lumbar region (two, 16.7%), pelvis (three, 25%), lower limbs (four, 33.3%), and upper limbs (one, 8.3%). All patients underwent surgery, and histopathology showed phosphaturic mesenchymal tumors in each. Postoperatively, serum phosphorus concentrations normalized within 2-7 days in 11 patients. With follow-ups of 1-41 months, surgery was effective in 10 patients. One patient developed local recurrence and another had metastases. CONCLUSIONS: Locating tumors responsible for tumor-induced osteomalacia is often challenging. Although complete tumor resection confers a good prognosis in most patients, surveillance for recurrence and metastasis is necessary. Before surgery or when surgery is not indicated, oral phosphate can alleviate symptoms and metabolic imbalance.

Delayed High-dose Methotrexate Excretion and Influencing Factors in Osteosarcoma Patients.

BACKGROUND: High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is "gold standard" therapy for osteosarcoma. Plasma concentrations of methotrexate (MTX) are closely related to its efficacy and toxicity. Delayed excretion of MTX can lead to serious adverse reactions that may result in treatment cessation, irreversible organ damage, and death. This study focused on the incidence of delayed excretion of MTX in Chinese osteosarcoma patients. METHODS: A total of 1277 osteosarcoma patients were treated with HD-MTX chemotherapy (4291 cycles) from 2010 to 2015. Factors that could influence delayed excretion of MTX (gender, age, number of chemotherapy cycles, and serum concentration of MTX) were analyzed. RESULTS: The incidence of delayed excretion of MTX (serum concentrations at 24 h [C24 h] >5 µmol/L) and severe delayed excretion of MTX (C24 h >20 µmol/L) were 6.19% and 0.86% per patient, and 2.31% and 0.26% per cycle of treatment, respectively. The incidence of severe delayed excretion of MTX was associated with gender, age, and C24 h. CONCLUSIONS: Precaution of delayed excretion of MTX is needed during osteosarcoma treatment using HD-MTX. An optimal individualized rescue strategy can be created with consideration of gender, age, and C24 h.

Is There a Reliable Method to Predict the Limb Length Discrepancy after Chemotherapy and Limb Salvage Surgery in Children with Osteosarcoma?

BACKGROUND: For a child with osteosarcoma, prediction of the limb length discrepancy at maturity is important when planning for limb salvage surgery. The purpose of this study was to provide a reliable prediction method. METHODS: A retrospective review of Chinese children receiving chemotherapy for osteosarcoma before skeletal maturity was conducted. Standing full-length radiographs of the lower extremity were used for length measurements. Length-for-age curves were constructed using the LMS method. The lower limb multiplier for a specific age and gender was calculated using the formula M = Lm/L, where M was the gender- and age-specific multiplier, Lmwas the bone length at maturity, and L was the age-specific bone length. Prematurity and postmaturity radiographs were used to assess the accuracy of the prediction methods. RESULTS: A total of 513 radiographs of 131 boys and 314 radiographs of 86 girls were used to calculate the coefficients of the multiplier. The multipliers of 8-, 9-, 10-, 11-, 12-, 13-, 14-, 15-, 16-, 17-, and 18-year-old boys after chemotherapy for osteosarcoma were 1.394, 1.306, 1.231, 1.170, 1.119, 1.071, 1.032, 1.010, 1.004, 1.001, and 1.000, respectively; while for girls at the same ages, the multipliers were 1.311, 1.221, 1.146, 1.092, 1.049, 1.021, 1.006, 1.001, 1.000, 1.000, and 1.000, respectively. Prematurity and postmaturity femoral and tibial lengths of 21 patients were used to assess the prediction accuracy. The mean prediction error was 0 cm, 0.8 cm, and 1.6 cm for the multiplier method using our coefficients, Paley's coefficients, and Anderson's method, respectively. CONCLUSIONS: Our coefficients for the multiplier method are reliable in predicting lower limb length growth of Chinese children with osteosarcoma.

Computer Navigation-aided Resection of Sacral Chordomas.

BACKGROUND: Resection of sacral chordomas is challenging. The anatomy is complex, and there are often no bony landmarks to guide the resection. Achieving adequate surgical margins is, therefore, difficult, and the recurrence rate is high. Use of computer navigation may allow optimal preoperative planning and improve precision in tumor resection. The purpose of this study was to evaluate the safety and feasibility of computer navigation-aided resection of sacral chordomas. METHODS: Between 2007 and 2013, a total of 26 patients with sacral chordoma underwent computer navigation-aided surgery were included and followed for a minimum of 18 months. There were 21 primary cases and 5 recurrent cases, with a mean age of 55.8 years old (range: 35-84 years old). Tumors were located above the level of the S3 neural foramen in 23 patients and below the level of the S3 neural foramen in 3 patients. Three-dimensional images were reconstructed with a computed tomography-based navigation system combined with the magnetic resonance images using the navigation software. Tumors were resected via a posterior approach assisted by the computer navigation. Mean follow-up was 38.6 months (range: 18-84 months). RESULTS: Mean operative time was 307 min. Mean intraoperative blood loss was 3065 ml. For computer navigation, the mean registration deviation during surgery was 1.7 mm. There were 18 wide resections, 4 marginal resections, and 4 intralesional resections. All patients were alive at the final follow-up, with 2 (7.7%) exhibiting tumor recurrence. The other 24 patients were tumor-free. The mean Musculoskeletal Tumor Society Score was 27.3 (range: 19-30). CONCLUSIONS: Computer-assisted navigation can be safely applied to the resection of the sacral chordomas, allowing execution of preoperative plans, and achieving good oncological outcomes. Nevertheless, this needs to be accomplished by surgeons with adequate experience and skill.

The Surgical Treatment and Outcome of Nonmetastatic Extremity Osteosarcoma with Pathological Fractures.

BACKGROUND: Recent studies have suggested that the presence of a pathological fracture does not impact on oncologic outcomes and the feasibility of limb salvage surgery (LSS) in appropriately selected patients when combined with neoadjuvant chemotherapy. These have largely been single institutional studies with limited numbers. The Eastern Asian Musculoskeletal Oncology Group reviewed the data from three large volume Asian orthopedic oncology centers to determine whether the presence of a pathologic fracture affected outcomes in osteosarcoma patients. METHODS: A retrospective review of the data was conducted. Ninety-five cases of nonmetastatic extremity osteosarcoma with a pathological fracture and 887 cases without fracture treated during the same period were compared. RESULTS: In the fracture group, the LSS rate was 62.1%, and the rate of amputation was 37.9%. In the nonfracture group, the LSS rate was 74.7%, and the amputation was 25.3%. In patients with a pathologic fracture, the rate of local recurrence for LSS and amputation groups was 8.5% and 2.8%, respectively. In this group, the 5-year survival in the LSS group was 66% as against. 46.8% in the amputation group. CONCLUSIONS: Our study suggests that surgically treated patients with pathologic fractures in osteosarcoma have adequate local control and do not have a poorer outcome compared to patients without a fracture. Though osteosarcoma with a pathologic fracture is not a contraindication for limb salvage, appropriate case selection is important when deciding local control options to ensure adequate oncologic clearance.

Radiofrequency ablation under 3D intraoperative Iso-C C-arm navigation for the treatment of osteoid osteomas.

OBJECTIVE: To evaluate the efficacy of intraoperative three-dimensional (3D) Iso-C C-arm-navigated percutaneous radiofrequency ablation (RFA) of osteoid osteomas. METHODS: 35 patients (20 males and 15 females) with osteoid osteomas underwent treatment with intraoperative 3D Iso-C C-arm navigation-guided RFA. The tumour was first biopsied for pathological examination, the core needle was removed and the RFA needle was inserted into the nidus. Post-operative X-rays and CT scans were performed to evaluate the degree of ablation and to assess for recurrence at 3-month follow-up. Patients also completed a visual analogue scale (VAS) both pre-operatively and 3 days post-operatively to subjectively assess pain. RESULTS: Pathological diagnosis confirmed osteoid osteoma in 19 cases. The other 16 cases were not pathologically diagnosed owing to inadequate biopsy specimens. In all cases, localized pain was immediately relieved following RFA. Patients reported significantly decreased pain, with mean pre-operative VAS scores of 3.4 reducing to 0.80 at 3 days post-operatively and further to 0.06 at 3-month follow-up (p < 0.05). The mean follow-up time was 15.5 months (range: 3-38 months). CONCLUSION: 3D Iso-C C-arm navigation-guided RFA is a safe and effective option for the treatment of osteoid osteomas and may be considered in place of intraoperative CT-guided and open resection. ADVANCES IN KNOWLEDGE: C-arm image-guided percutaneous RFA mitigates the need for pre-operative CT as well as intraoperative scintigraphy, provides real-time imaging of the anatomy, facilitates accurate resection of the tumour and enables immediate confirmation of excision.

[Alkaloids from cervi cornu pantotrichum and its effect on murine splenocytes proliferation].

OBJECTIVE: To study the alkaloids of Cervi Cornu Pantotrichum and its effect on murine splenocytes proliferation. METHODS: The constituents isolation and purification from Cervi Cornu Pantotrichum was carried out by reported column chromatography including Sephadex LH-20 and MCI (CHP20P) and their structures were elucidated on the basis of spectral compounds. The method of MTT was used to examine the effects of eight alkaloids and total alkaloids content (TAC) of Cervi Cornu Pantotrichum on murine splenocytes proliferation. RESULTS: Eleven compounds were isolated from Cervi Cornu Pantotrichum, and their structures were identified as follows: uracil (1), hypoxanthine (2), uridine (3) inosine (4), guanosine (5), 2'-deoxyguanosine (6), guanine (7), thymidine (8), thymine (9), cytidine (10) and adenosine (11). By the experiment of murine splenocytes proliferation activity in vitro, the results showed that the total alkaloids, uracil and adenosine had significantly promoted the proliferation of mouse spleen cells. CONCLUSION: Compounds 4 - 11 are isolated from Cervi Cornu Pantotrichum for the first time. The total alkaloids is one of the material basis of immunomodulatory effects of Cervi Cornu Pantotrichum, and uracil and adenosine are the most active.

[Diagnosis and treatment of giant cell tumor of bone in skeletal immature patients].

OBJECTIVE: To demonstrate the common characteristics of giant cell tumor of bone in immature skeletons. METHODS: From 1989 to 2009, the 8 skeletal immature patients were pathologically diagnosed with giant cell tumor (GCT) in our department, which accounted for 1.3% (8/621) of all GCT patients in an extremity. All patients were identified with an open epiphyseal plate by retrospective review of the radiograph, CT or MRI by senior consultants. Oncological and functional outcome were followed for a mean 44.1 months. There were 5 boys and 3 girls. The mean age was 13.8 years. All cases had a primary lesion. The distal femur is the most common site involved (3 cases), followed by the proximal tibia (2 cases). The proximal humerus, the distal tibia and the distal radius accounted for 1 case respectively. Oncological and functional outcome are followed for a mean 44.1 months. RESULTS: All lesions were lytic. Six lesions involved both the epiphysis and metaphysis. Two lesions located in the metaphysis area. Six lesions were treated with extended curettage and were reconstructed with allograft and (or) bone cement. Internal fixations were used in 2 cases. Two cases were treated with segmental resection. And one was reconstructed with cement spacer and the other one with segmental allograft and internal fixation. One patient (1/6) developed a bone recurrence after extended curettage. No extremity deformity and discrepancy were found during the follow up after the curettage. No metastasis was found during the follow up. CONCLUSION: Histologically GCT occurs in skeletal immature bone has the same pathological appearance but radiologically has its unique features. These lesions share same behavior as that in adults. A low local recurrence rate and good function can be achieved after a proper surgery.

Subchondral bone grafting reduces degenerative change of knee joint in patients of giant cell tumor of bone.

BACKGROUND: Giant cell tumors (GCTs) most commonly occur around the knee. The most beneficial procedure for this disease has been extensive curettage with reconstruction. However, since many GCTs may compromise the subchondral bone, surgery can further jeopardize the articular cartilage and result in secondary osteoarthritis. In this study, we aimed to determine the factors associated with the development of degenerative arthritis and the effect of bone grafting on the prevention of secondary osteoarthritis. METHODS: We retrospectively analyzed 76 patients with GCT around the knee. The mean age at first diagnosis was 31.1 years. Surgical treatments included extensive curettage and cementation with or without bone grafting in the subchondral bone. Patient follow-up was a median duration of 35 months, ranging from 18 to 113 months. RESULTS: The local recurrence rate was 5.3% (4/76). Secondary degenerative changes occurred in 30.3% (23/76) of the patients. Less than 10 mm of the residual thickness of the remaining subchondral bone was correlated with secondary degenerative changes in 57 patients (P < 0.001). Of these 57 patients, 56.5% (13/23) treated with bone cement reconstruction alone developed secondary degenerative changes; following bone grafting, the rate decreased to 29.4% (10/34), with a statistically significant difference (P = 0.041). CONCLUSIONS: GCT patients with less residual thickness of the subchondral bone are more likely to develop degenerative arthritis after curettage. Bone grafting in the subchondral bone area is recommended when the residual thickness of the subchondral bone is less than 10 mm.