Analysis of risk factors for 1-year survival rate in patients with spinal metastasis secondary to lung cancer / 中华骨科杂志

Objective:To investigate the risk factors for 1-year survival rate in patients with spinal metastasis secondary to lung cancer.Methods:The data of 343 patients with spinal metastases secondary to lung cancer from January 2011 to December 2018 were retrospectively studied. There were 188 males (54.8%) and 155 females (45.2%) with an average age of 59.47±10.21 years old (range 23-91 years). The patients were divided into operation group (150 cases, 43.7%) and non operation group (193 cases, 56.3%). The demographics, types of primary tumor, non spinal metastasis, visceral metastasis, spinal metastasis and segments, pathological fractures of vertebra, Frankel classification, physical function status (Karnofsky performance scale, KPS), visual analogue score (VAS), the spinal instability neoplastic score (SINS) were recorded and analyzed. The impact of different treatments on the survival prognosis of patients with spinal metastasis was evaluated. The independent factors affecting survival in those patients were analyzed by Cox proportional hazards regression model.Results:The peak incidence of spinal metastases was found in the age group of 46-60 years (43.7%, 150/343). 38.5% (132/343) of the patients had pathological fractures of the involved vertebral body. 58.3% (200/343) of the patients had extraspinal bone metastasis. 36.2% (124/343) of the patients had visceral metastasis. Among the primary tumors, adenocarcinoma was the most common tpye (61.5%, 211/343), followed by large cell lung cancer (12.5%, 43/343), small cell lung cancer (6.4%, 22/343), squamous cell cancer (6.1%, 21/343) and mixed cell lung cancer (5.3%, 18/343). The type of lung cancer cells in about 8.2 (28/343) patients was unknown. Among the surgical patients, 21 patients underwent minimally invasive surgery (14.0%), 28 patients underwent simple decompression surgery (18.7%), 76 patients underwent separation surgery (50.7%), and 25 patients underwent radical surgery (16.6%). 59.3% (89/150) of the patients had a better neurological function than before surgery. The average survival time of all patients was 9.88 months with the median survival time of 8 (5,14) months. The survival rates were 62.1% (213/343), 30.0% (103/343), and 3.8% (13/343) at 6, 12, and 24 months, respectively. The average survival time of patients in the operation group was 10.24 months with the median survival time of 9 (5, 15) months, and the average survival time of patients in the non operation group was 9.41 months with the median survival time of 7 (5, 13) months with no significant difference between the groups (χ 2=0.300, P=0.584). Multivariate Cox proportional hazard regression model analysis showed that radiotherapy [ HR=1.913, 95% CI(1.471, 2.488), P<0.001], chemotherapy [ HR=1.313, 95% CI(1.040, 1.658), P=0.022], targeted drug therapy [ HR=1.683, 95% CI(1.221, 2.319), P=0.001], KPS [ HR=1.593, 95% CI(1.140, 2.225), P=0.006] and pathological type (non-small cell lung cancer) were independent factors affecting the 1-year survival rate of patients with spinal metastasis secondary to lung cancer [ HR=0.322, 95% CI(0.225, 0.460), P<0.001] with significant difference. Conclusion:Surgical treatment can improve both the neurological function and general status of patients with spinal metastasis. Treatments of radiotherapy, chemotherapy, and targeted drug therapy can significantly improve 1-year survival rate, while a KPS less than 50 points and a primary lung cancer other than adenocarcinoma were independent risk factors reducing 1-year survival rate.

An Amendment to the Neidre and MacNab Classification System for Lumbosacral Nerve Root Anomaly and Its Implication in Percutaneous Endoscopic Lumbar Discectomy.

BACKGROUND: Lumbar disc herniation complicated with nerve root anomaly presents great challenges to diagnosis and treatment. Improper selection of surgical procedures may cause inferior outcomes and neurologic injury. CASE DESCRIPTION: A 66-year old man presented with low back pain and radicular symptoms involving bilateral L5 and S1 nerve roots. Instead of percutaneous endoscopic lumbar discectomy, aggressive decompression was carried out because of a deviation between the examination and imaging findings. Surgical detection disclosed a confluent nerve root comprising 2 adjacent contributions that arose from the thecal sac exiting from the left L5/S1 foramen, in the absence of the root otherwise exiting through the caudal foramen. We found that the overwhelming left radicular symptoms were attributable to compression on this swelling anomalous root by a narrowed L5/S1 root cannula. Aggressive decompression and distraction of the intervertebral space successfully released the nerve root. Twenty months postoperatively, the patient experienced evident relief of the radicular symptoms and improvement of muscle strength with no complication. CONCLUSIONS: Lumbosacral nerve root anomaly should be remembered and ruled out before selecting surgical methods. Inappropriate procedures can not alleviate the symptoms associated with the anomalous roots and may expose such patients to the risk of neural injury. In clinical practice, surgeons should select percutaneous endoscopic lumbar discectomy with caution, and stop the procedure instantly when unexplainable radicular irritation is evoked.

Emphasis on precision intelligent medical research, positive response to the development trend of bone tumor diagnosis and treatment / 中华骨科杂志

Since the implementation of surgery-based comprehensive treatment, there have been great advances and breakthroughs in the diagnosis and treatment of bone tumors. The survival rate of primary malignant bone tumors has significantly improved, for example, the 5-year survival rate of osteosarcoma has increased from 5%-20% to 60%-70%. Characteristics of bone tumors are as follows: (1) have a wide range of lesion sites; (2) various types; (3) high heterogeneity; (4) structural reconstruction is as important as functional reconstruction; (5) metastatic tumors are more common than primary tumors. Based on the characteristics above, the combination of clinical, imaging and pathology is the basic principle in the diagnosis of bone tumors; Following the principle of tumor resection to achieve local control, it is necessary not only to carry out effective reconstruction of bone and soft tissue structural defects, but also to obtain as perfect motor function as possible. Due to the development of genetic research, bioinformatics technology, digital medicine and computer technology, the diagnosis and treatment of bone tumors have entered the stage of precision medicine with four characteristics: accuracy, punctuality, sharing and individualization. Using the multi-omics technology of genomics, transcriptomics, proteomics and metabolomics to explore the mechanism of the occurrence and development of bone tumors and find new target genes provides a direction for the application of precision medicine in bone tumors in the future. The application of Wise Information Technology of med based on artificial intelligence is of great significance for the auxiliary diagnosis and precise treatment.

Imaging evaluation of the efficacy and prognosis of neoadjuvant chemotherapy for osteosarcoma / 中国医师杂志

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Neoadjuvant chemotherapy is an important part of the standard treatment mode for osteosarcoma. Preoperative evaluation of the effect of neoadjuvant chemotherapy is of great significance to the selection of surgical plan and the adjustment of subsequent treatment plan. Imaging evaluation method is one of the important ways to evaluate the efficacy of neoadjuvant chemotherapy and the prognosis of patients. It has the advantages of simple, quick and non-invasive, and has become a research hotspot.

Design and clinical application of the distal femur spherical motion axis hinge knee prosthesis / 中华骨科杂志

Objective:To investigate the feasibility and early clinical efficacy of spherical motion axis hinge knee prosthesis to reconstruct distal femoral bone defects.Methods:A retrospective analysis was performed on 16 patients admitted to PLA 960th Hospital and Tianjin Hospital from October 2019 to November 2021, including 8 males and 8 females, with an average age of 43.3±17.8 years (range, 15-71 years). There were 13 patients of primary tumors of the distal femur and 3 patients of postoperative revision of knee joint prostheses. Among the 13 patients with distal femur tumors, there were 6 cases of osteosarcoma, 5 cases of giant cell tumor of bone, 1 case of leiomyosarcoma and 1 case of chondrosarcoma. The reasons for revision after prosthesis replacement in 3 cases were: 2 cases of aseptic loosening after tumor-type prosthesis and 1 case of periphery fracture of surface artificial knee prosthesis. A spherical shaft rotary hinged knee prosthesis was designed and fabricated to reconstruct postoperative femoral defects in 16 patients. Follow up regularly after the operation, recheck the X-ray film to evaluate the lower limb force line, evaluate the quality of life after the operation with the Chinese version of 36-item short-form (SF-36), and evaluate the postoperative limb function with the Musculoskeletal Tumor Society (MSTS) 93 evaluation system.Results:All 16 patients were successfully placed with prostheses, and except for 2 patients undergoing total femoral replacement, the length of bone defects was 18.2±11.7 cm (range, 8.6-47.1 cm) in other 14 patients, and the operation time was 138±19 min (range, 110-170 min), the intraoperative blood loss was 211±118 ml (range, 100-500 ml). The postoperative full length orthostatic X-ray film of the lower limbs showed that the distance between the mechanical axis of the lower limb and the center of the knee joint was 0.1 (0, 0.7) cm in 16 patients, and the hip-knee ankle angle was 179.0°±2.3°(range, 173.3°-182.2°). The patients were followed up for 12-36 months. No prosthesis complications were found in 16 patients. The SF-36 score was 56.7±7.0 (range, 42.7-67.4) for physiological function and 54.1±7.6 (range, 40.5-66.3) for psychological function. The maximum knee flexion angle was 120.0°±15.6° (range, 95°-130°). The MSTS 93 score of 15 patients with tumor was 25.0±1.7 (range, 22-28), including 7 excellent and 8 good. One patient developed liver and lung metastases 10 months after surgery and died 18 months after surgery. The remaining patients, as of the last follow-up, were alive and had no local recurrence or distant metastases. Tumor-free survival time was 25.8±8.4 months (range, 12-36 months).Conclusion:The spherical motion axis hinge knee prosthesis reconstruction for distal femoral bone defects is simple and fast in intraoperative prosthesis installation, and there are no prosthetic related complications during short-term follow-up. The clinical efficacy is satisfactory.

Analysis and revision surgical strategy of tumor prosthesis of knee joint / 中华骨科杂志

Objective:To explore the reasons for revision of tumor prosthesis of knee joint and summarize the experience of revision surgery.Methods:We conducted a retrospective study of 33 patients who underwent revision surgery for tumor prosthesis of knee joint in Tianjin Hospital and the 960th Hospital of the People's Liberation Army Hospital from June 2004 to June 2018. There were 25 male and 8 female patients, the mean age was 45±13.1 years (range 19-64 years) at the time of revision. Histological diagnosis was giant cell tumor in 17 patients, osteosarcoma in 9 patients, malignant fibrous histiocytoma in 3 patients and one for each of chondrosarcoma, peripheral schwannoma, ligamentoid fibroma and bone metastases. The reasons for revision were aseptic loosening in 23 cases, dislocation, stem breakage and periprosthetic fracture in 2 cases, infection in 3 cases, and local recurrence in 1 case. The general outcome, oncological outcome, reasons for prosthesis revision, postoperative limb function, and complications were summarized.Results:The median follow-up of the 33 patients was 48.0 (24.0, 107.0) months. The most common reason for revision was aseptic loosening (88%, 29/33), followed by infection (9%, 3/33) and local recurrence (3%, 1/33). The MSTS of 32 patients with survival more than 1 year was 24.28±4.74 points (range 9-30 points), which was statistically different from preoperative 11.78±5.23 points (range 4-21 points) ( t=10.02, P<0.001). The postoperative median TESS score of 32 patients with survival more than 1 year was 86.67(80.00, 91.67) points, and the preoperative median score was 56.0(43.17, 65.33) points, which was statistically significant ( Z=6.78, P<0.001). Postoperative complications occurred in 12 patients, most commonly mechanical problems (15%, 5/33) and infection (15%, 5/33), followed by local recurrence (6%, 2/33), with an overall complication rate of 36% (12/33). Conclusion:The main reason for revision of tumor prosthesis of knee joint is aseptic loosening. Revision surgery can achieve ideal postoperative function and should be the first choice for failure of prosthesis after initial replacement.

Chitinase-3-like protein 1 plays a role in lumbar facet joint degeneration / 中华骨科杂志

Objective:To investigate the effect of CHI3L1 on the biological function of chondrocytes and its role in lumbar facet joint degeneration.Methods:The human lumbar facet joint articular cartilage were collected, and the relative mRNA expression of CHI3L1 gene detected by quantitative fluorescence PCR. Then explored the correlation between joint degeneration and gender, age and relative mRNA expression of CHI3L1. Human chondrocytes were cultured in vitro. The effects of CHI3L1 on chondrocyte proliferation, cycling, and apoptosis, as well as expression of related inflammatory factors, were investigated. The mechanism by which CHI3L1 regulates the degeneration of articular cartilage was investigated using the signal transduction pathway protein chip.Results:There was a positive correlation between the grade of degeneration in lumbar facet joint and the relative expression of CHI3L1 gene mRNA ( r=0.76, P<0.001). There was no correlation with the patient's gender ( r=-0.12, P=0.500). A positive correlation between the age of patients and the relative expression of CHI3L1 gene mRNA was found ( r=0.47, P=0.005). Compared with the non-degenerative group, the expression of CHI3L1 gene mRNA significantly increased in the degenerative group, and the expression of CHI3L1 gradually increased with the aggravation in the grade of degeneration ( F=18.90, P<0.001). Compared with the non-degenerative group, the chondrocytes in the CHI3L1 group had significantly lower proliferation at 48 h (OD 490/fold=7.132), 72 h (OD 490/fold=4.803), 96 h (OD 490/fold=2.431) and 120 h (OD 490/fold=0.009). The ratio of chondrocytes in G1 phase, S phase and G2/M phase were 85.03%±3.05%, 12.78%±2.29% and 0.90%±0.76% in the CHI3L1 group, and 73.93%±2.73%, 22.81%±1.93% and 0.99%±0.87% in control group, respectively. There were significant differences in the percentage of chondrocytes in G1 phase ( t=4.70, P<0.001) and S phase ( t=5.80, P<0.001) between the two groups. The percentages of apoptosis in chondrocyte in CHI3L1 group and control group were 8.64%±0.76% and 5.68%±1.13%, which has a statistically difference ( t=4.47, P<0.001). The expression of IL-6 in chondrocytes of CHI3L1 group was 49.60±0.01 pg/ml, which was higher than that of 47.88±0.01 pg/ml in the control group ( t=132.70, P<0.001). The expression of TNF-α was 95.93±0.02 pg/ml, which was higher than 90.69±0.02 pg/ml in the control group ( t=376.10, P<0.001). There was significant difference in expression of IL-6 in chondrocytes between the CHI3L1 group and the control group ( t=132.72, P<0.001). The expression of TNF-α ( t=376.10, P<0.001) was statistically difference. Protein chip detected 53 proteins with significant differences in expression and 43 proteins with significant differences in protein phosphorylation levels. Bioinformatics analysis was used to identify 16 signaling pathways in which the above different proteins might be involved, including ErbB, PI3K, Akt, Ras, JAK, STAT3, MAPK pathway. In the MAPK pathway, the expression of MAPK1 and RAF1 proteins was higher in the chondrocytes of the CHI3L1 group than in the control group (1.094±0.00 vs. 0.814±0.00, 0.988±0.00 vs. 0.786±0.00; t=103.16, P<0.001; t=54.32, P<0.001). Compared with the control group, the expression of MAPK1 and RAF1 proteins was significantly increased in the chondrocytes of the CHI3L1 group. Conclusion:The expression of CHI3L1 is corrected to articular cartilage degeneration. CHI3L1 is able to inhibit the proliferation of articular chondrocytes, which regulated the cycling of chondrocytes from G1 phase to S phase, promote the apoptosis of chondrocytes, and promote the expression of IL-6 and TNF-α in chondrocytes. Regulation of chondrocytes biological function through the MAPK pathway, which is a potential biomarker for the clinical diagnosis and treatment of lumbar joint degeneration.

The trend of clinical and pathological characteristics and surgical treatment in patients with spinal metastases: A multicenter retrospective study / 中华骨科杂志

Objective:To retrospectively analyze the patients with spinal metastases who received surgical intervention and summarize the evolution of their clinical and pathological characteristics and surgical methods.Methods:The data of 703 patients with spinal metastases from January 2007 to December 2018 were collected retrospectively. There were 395 males (56.19%, 395/703) and 308 females (43.81%, 308/703) with an average age of 58.14±11.46 years (range 13-84 years). According to the degree of invasion and thoroughness of tumor resection, the surgical methods could be divided into minimally invasive surgery, decompression surgery, separation surgery, piecemeal resection and total en-bloc spondylectomy surgery. The operative methods were minimally invasive surgery in 89 cases (12.66%), decompression surgery in 96 cases (13.66%), separation surgery in 303 cases (43.10%), piecemeal resection in 182 cases (25.89%) and total en-bloc spondylectomy in 33 cases (4.69%). To analyze the trend of the clinical, pathological types and surgical treatment of patients with spinal metastases over the years, and determine the relevant factors affecting the decision-making of surgical methods by multivariate logistic regression.Results:The ratio of male to female was 1.28:1. 39.54% (278/703) of patients with single-segment involvement in 703 patients, 24.04% (169/703) of patients with double-segment metastasis and 36.42% (256/703) of patients with multi-segment metastasis. The most common type of primary tumor was lung cancer (34.57%, 243/703), followed by breast cancer (8.25%, 58/703), myeloma (8.11%, 57/703), gastrointestinal tumor (6.82%, 48/703) and renal malignant tumor (6.40%, 45/703). From 2007 to 2018, there was no significant difference in the percentage change of different age, gender and primary tumor source composition (age: χ 2=14.01, P=0.233; gender: χ 2=35.73, P=0.341; primary tumor: χ 2=120.09, P=0.074). The percentage of patients with sacrococcygeal metastasis decreased from 20.00% in 2008 to 1.89% in 2017 and the difference was statistically significant (χ 2=8.09, P=0.005). The percentage of patients with multi-level metastasis increased from 26.67% in 2008 to 52.83% in 2017, and the difference was statistically significant (χ 2=7.23, P=0.007). The percentage of patients with minimally invasive surgery decreased from 25.00% in 2007 to 5.88% in 2018, and the percentage of patients with segmented resection decreased from 53.33% in 2008 to 10.29% in 2018. The proportion of the two surgical methods showed a significant downward trend, and the differences were statistically significant (minimally invasive surgery: χ 2=1.46, P=0.026; segmented resection surgery: χ 2=19.56, P<0.001). The percentage of patients undergoing separation surgery increased from 13.33% in 2008 to 64.71% in 2018, and the proportion of patients undergoing total en-bloc spondylectomy increased from 0 in 2007 to 10.29% in 2018. Both surgical methods showed a significant growth trend and the differences were statistically significant (separation surgery: χ 2=27.09, P<0.001; χ 2=4.16, P=0.042). Multivariate Logistic regression analysis showed that age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score were independent factors influencing surgical decision-making ( P<0.05). Conclusion:With different time and age, the invasiveness and thoroughness of surgery are increasing, which shows that the percentage of patients who underwent separation surgery and to-tal en-bloc spondylectomy is significantly increasing. Age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score are independent factors affecting surgical decision-making.

The clinical value of the New England spinal metastases score system in predicting the survival of patients with spinal metastases / 中华骨科杂志

Objective:To evaluate the clinical value of the New England spinal metastasis score (NESMS) in predicting the prognosis of patients with spinal metastases by retrospectively analyzing the medical records of multicenter spinal metastases in China.Methods:The data of 179 patients with spinal metastases from January 2008 to December 2018 were retrospectively collected. There were 108 males (60.3%) and 71 females (39.7%) with an average age of 59.79±10.88 years old (range 27-84 years). The patient demographic characteristics, primary tumor type, spinal metastases and segments, vertebral pathological fractures, neurological Frankel classification, physical function status, Karnofsky performance scale (KPS), visual analogue score (VAS), the spinal instability neoplastic score (SINS), modified Bauer score, NESMS score, Tomita score and modified Tokuhashi score were collected. The clinical value of NESMS score, Tomita score and modified Tokuhashi score in predicting the survival of patients with spinal metastases were compared. The independent factors affecting survival in these patients were analyzed by Cox proportional hazards regression model.Results:Among the 179 patients, the peak incidence of spinal metastases was in the age group of 61-75 years (45.3%, 81/179) of all patients. Lung cancer was the most common primary tumor (46.9%, 84/179). 40.8% (73/179) of patients had multi-segment metastasisand thoracic spine was the most common site with single-site metastasis (26.3%, 47/179). 28.5% (51/179) of the patients had visceral metastases and 52.0% (93/179) of the patients had extraspinal bone metastases. 31.3% (56/179) of the patients had pathological fractures of the involved vertebral bodies.114 patients received surgical treatment (63.4%). The mortality rates in 3-months, 6-months and 1-year were 22.4% (40/179), 51.4% (92/179) and 77.1% (138/179), respectively. The median survival time of patients with NESMS score of 0-3 was 3, 4, 8, and 10 months respectively with the mean survival time was 3.60±2.10, 6.77±3.39, 9.69±5.71 and 10.53±6.25 months. The 1-year mortality rates were 100% (13/13), 87.5% (42/48), 71.6% (63/88) and 66.7% (20/30) respectively. The consistency of NESMS score, Tomita score and modified Tokuhashi score in predicting survival of all patients was 0.63, 0.58 and 0.55, respectively. For patients with spinal metastases, the NESMS score was better than the Tomita score and modified Tokuhashi score in predicting survival at 3-months (AUC=1.00, 0.63, 0.42) and 6-months (AUC=0.71, 0.63, 0.45). But the accuracy of Tomita score was best in predicting survival at 1-year (AUC=0.66, 0.61, 0.38). Multivariate Cox proportional hazards regression model analysis showed that growth rate of primary tumor, neurological function Frankel score, albumin level and surgical treatment were independent factors affecting the survival time of patients with spinal metastases ( P<0.05). Conclusion:The consistency and accuracy of NESMS score in predicting survival of patients with spinal metastases are better than Tomita score and modified Tokuhashi score, especially in predicting 3- and 6-month survival. The growth rate of primary tumor, Frankel classification, albumin level and surgical treatment were independent factors affecting the survival time of patients with spinal metastases.

Effects of cyclic tensile stress on biological function and degeneration of nucleus pulposus cells / 中华骨科杂志

Objective:To investigate the effects of cyclic tensile stress on the function and degeneration of nucleus pulposus cells.Methods:The human primary nucleus pulposus cells were isolated and cultured. The cyclic tensile stress (100 000 μ?, 10% tensile strain, 0.1 Hz, 8 640 cycles) was loaded on the cells for 24 h. The proliferation of the cells was examined by MTT method. The cell cycle and apoptosis were detected through flow cytometry. Gene expression profile chip was used to detect the differentially expressed genes between the tensile stress group and control group. The function of these gene was analyzed by bioinformatics. The expression of inflammatory related factors, TGF-β, matrix degrading enzymes and extracellular matrix molecules were examined by qRT-PCR.Results:The cyclic tensile stress significantly promoted proliferation and cell cycle of nucleus pulposus cells. The cell percentage of S phase ( t=5.336, P<0.05) and G2/M phase ( t=7.288, P<0.01) was significantly different between the tensile stress group and control group. The cyclic tensile stress inhibited apoptosis of nucleus pulposus cells (8.56%±0.48% vs 10.63%±0.32%, t=4.474, P<0.05). A total of 866 differentially expressed genes were detected. Gene ontology analysis showed the roles of these genes in cells including focal adhesion, extractable matrix, membrane raft, condensed chrome kinetochore, cytoskeleton, etc. The cyclic tensile stress significantly affected the mRNA expression of inflammatory related factors, TGF-β genes, matrix proteinase and extracellular matrix molecules. Compared with the control group, the mRNA expression of inflammatory related factors IL15 ( t=5.379, P<0.05), IGF1 ( t=5.454, P<0.05) and IGFBP7 ( t=13.57, P<0.01) were significantly decreased in the tensile stress group; The mRNA expression of TGF-β genes TGFB1 ( t=6.931, P<0.05), TGFB2 ( t= 15.56, P<0.01) and TGFB3 ( t=7.744, P<0.05) were significantly increased in the tensile stress group; The mRNA expression of matrix proteinase ADAMTS3 ( t=5.241, P<0.05) and MMP19 ( t=24.72, P<0.01) were significantly decreased, and TIMP3 ( t=8.472, P<0.01) increased in the tensile stress group; The mRNA expression of extracellular matrix molecules COL2A1 ( t=5.871, P<0.05), FLRT2 ( t=5.216, P<0.05) and FN1 ( t=4.289, P<0.05) were significantly increased. Conclusion:The cyclic tensile stress promoted cell cycle and proliferation and inhibited apoptosis of nucleus pulposus cells. The cyclic tensile stress may affect the function and degeneration of nucleus pulposus cells by regulating the expression of inflammatory related factors, TGF-β, matrix degradation enzymes and ECM molecules.

The basic principle and clinical outcomes of epiphysis preservation limb salvage in the treatment of limb osteosarcoma in children and adolescents / 中华骨科杂志

Epiphyseal preservation limb salvage is a method for the treatment of limb osteosarcoma in children and adolescents.The purpose is to avoid the unequal length of bilateral limbs and improve the affected limb function without increasing the occurrence of life-threatening complications.Strictly following the indications is the key to ensure the success of the operation.Before operation,epiphyseal distraction or imaging method is used to determine the position of osteotomy in operation,which has reached the safe boundary of tumor resection.Many ways were used to repair the tumor bone defect.A lot of studies confirmed that all kinds of surgical methods have achieved satisfied clinical outcomes,but there are different surgical complications.Only when the epiphyseal plate and epiphysis are kept at the same time can the length of the limb be ensured to be equal;the result of intraepiphyseal osteotomy is that the block of bone growth leads to the unequal length of the limb.The biological reconstruction of bone defect can restore the length of limbs by bone lengthening after bone growth stops.

The basic principle and clinical outcomes of epiphysis preservation limb salvage in the treatment of limb osteosarcoma in children and adolescents / 中华骨科杂志

Epiphyseal preservation limb salvage is a method for the treatment of limb osteosarcoma in children and adolescents. The purpose is to avoid the unequal length of bilateral limbs and improve the affected limb function without increasing the occurrence of life-threatening complications. Strictly following the indications is the key to ensure the success of the operation.Before operation, epiphyseal distraction or imaging method is used to determine the position of osteotomy in operation, which has reached the safe boundary of tumor resection. Many ways were used to repair the tumor bone defect. A lot of studies confirmed that all kinds of surgical methods have achieved satisfied clinical outcomes, but there are different surgical complications. Only when the epiphyseal plate and epiphysis are kept at the same time can the length of the limb be ensured to be equal; the result of intra-epiphyseal osteotomy is that the block of bone growth leads to the unequal length of the limb. The biological reconstruction of bone defect can restore the length of limbs by bone lengthening after bone growth stops.

Reconstruction for long segment bone defect of long bone malignant tumor in teenagers / 中华骨科杂志

Objective:To explore the method and curative effect evaluation of repairing and rebuilding the long segmental bone defect after resection of long bone malignant tumors in adolescents.Methods:Reviewed our experience in 10 patients. Among them, 4 were male and 6 were female. The age was 10.2 years old (range, 6-16 years old). Including 7 cases of osteosarcoma, 3 cases of Ewing's sarcoma; 2 cases of humerus tumors, 7 cases of femoral tumors, and 1 case of tibial tumors-who presented between April 2015 and October 2019, in which the proportion of bone defect account for 71.4%-89.3% of the total length of diseased bone after tumor resection, with an average value of 80.9%. Considering the epiphyseal growth of young people, on the premise of ensuring enlarged tumor resection, we use traditional fibula autograft and prosthesis combined with steel plate, 3D printing design to retain the super-prosthesis of the epiphysis, and 3D printing bone trabecular was processed for the sake of making it grow successfully into the binding part of prosthesis and bone as we expect, simultaneously, the design of the short-force arm retaining the bilateral epiphysis can assit the steel plate and interlocking screws to enhance the stability.Results:The operation was completed successfully, and there were no complications such as nerve and blood vessel injury during the operation. After follow-up of 4-8 months, with an average follow-up of 22.9 months. One patient's review of X-ray film after 2 years of the operation showed that the transplanted fibula had a sign of bone resorption, and the internal fixation was in it's original position without obvious abnormalities. Two cases' auxiliary steel plates had fractured within one and a half to two years after surgery. With replacing the fractured steel plates, the internal fixation was good until now. According to the evaluation standards of the International Society of Limb Salvation: 2 cases of humerus osteosarcoma were respectively scored 23 points, 26 points, an average of 24.5 points; 4 cases of femoral osteosarcoma and 3 cases of femoral Ewing's sarcoma respectively scored 26 points and 25 points, 19 points, 30 points, 27 points, 24 points, 28 points (average, 25.6 points); 1 case of tibial osteosarcoma scored 26 points; all obtained relative satisfying treatment results.Conclusion:The combination of 3D printing and traditional machining techniques to produce an individualized long segmental prosthesis that preserves the epiphysis which applicated in the limb salvage treatment of bone malignant tumors can achieve excellent therapeutic effect.

Progress of Denosumab in the treatment of giant cell tumor of bone / 中华骨科杂志

Denosumab is a fully human monoclonal antibody on receptor activator of NF-κB ligand that has shown adjuvant treatment for giant cell tumour of bone (GCT).Clinical trials show that over 85％ of patients have significantly improved their clinical symptoms,imaging and histology.Currently mainly used for central axis bone such as the sacrum and spine of difficult surgical excision or limb recurrence or refractory GCT patients.Case reports have demonstrated complete response or tumor stabilization with denosumab,allowing for surgical procedures in simplify.However,the duration of the medication and the optimal therapeutic dose and long-term effects are not yet known.The local high recurrence rate after discontinuation of the drug remains a problem with the accumulation of clinical research,and the follow-up time is prolonged.More noteworthy is the possibility of pseudosarcoma,even malignant transformation after Denosumab treatment.This sarcoma transformation requires further controlled studies and long-term of follow-up to reach a definitive conclusion.In this paper,we retrospective analysis of the application status,imaging and histology related research of Denosumab in the treatment of GCT.Correct understanding of the value and clinical significance of this drug in GCT treatment requires a multi-center study and a long-term follow-up to evaluate the clinical value.

Total Claviculectomy as Treatment of Clavicular Ewing's Sarcoma: a Case Report and Literature Review / 中华骨科杂志

Objective To analyze the efficacy of total claviculectomy in the treatment of Ewing's sarcoma and to discuss the impact of clavicular reconstruction on the outcome.Methods The clinical records of a 13-year-old male patient with left clavicular Ewing's sarcoma were reviewed.The subject received 2 cycles (at an interval of 2 weeks) of neoadjuvant chemotherapy comprising cisplatin 120 mg/m2 (1 d),adriomycin 30 mg/m2 (3 d),and ifosfamide 2.0 g/m2 (5 d).Total claviculectomy was carried out without clavicular reconstruction and the patient underwent 9 cycles of subsequent chemotherapy.The appearance and function of the operated limb,radiological examinations of the surgical site,ECT bone scans and pulmonary CT were followed up.The literatures regarding the total and subtotal excision of the clavicle were reviewed to investigate the importance of clavicular reconstruction.Results After 23-months of follow-up,the patient was subjectively free of limb function compromise.Physical examinations indicated drooping of the operated shoulder by 2 cm,whereas the appearance was similar between both shoulders.Functionality of the operated limb was recovered.The motion of the left shoulder:abduction 90°,adduction 40°,anterior flexion 90°,extension 45°,internal rotation 80°,external rotation 60°,and no restriction of limb elevation.Manual muscle strength tests showed V/V muscle strength of the operated limb.American Shoulder and Elbow Surgeons' form (ASES) and Musculoskeletal Tumor Society (MSTS) score were 96 and 30,respectively.Postoperative X-ray films demonstrated mild thoracic scoliosis.The patient did not appear recurrence and metastasis.Conclusion Total claviculectomy is efficacious for treating clavicular Ewing's sarcoma.Clavicular reconstruction may not be imperative for treatment of clavicular malignancy because of the increased technical difficulty and great risk of complications.

Clinical application of segmental prosthesis in reconstruction of diaphyseal tumors / 中华骨科杂志

Objective To investigate the clinical value of segmental prosthesis in the repair of diaphyseal defect.Methods The clinical data and follow-up information of 40 patients who accepted segmental prosthesis reconstruction of long bone defects in limbs were collected from June 2010 to June 2017 in General Hospital of Jinan Military Commanding and Tianjin Hospital.The parameters for outcome evaluation including general information,surgical complications,Musculoskeletal Tumor Society (MSTS) functional score,survival and prostheses status were analyzed.Results Forty patients were underwent segmental prosthesis surgery,including 18 males and 22 females,with a median age of 64 years and the age range of 13-83 years.The surgery was performed on 28 cases of femur,8 cases of humerus,3 cases of tibia,and 1 cases of ulna.There were 5 cases of primary tumor,3 cases of multiple myeloma and 32 cases of metastatic tumor of bone,in which lung cancer,breast cancer,kidney cancer,liver cancer and colorectal cancer are common.Pathological fracture of surgical site occurred in 32 cases.The average osteotomy length was 93.5 mm.The shortest osteotomy was 60 mm and the longest osteotomy was 190 mm.The average operation time was 104.6 minutes.The median bleeding volume was 600 ml.The least bleeding was 200 ml and the most bleeding was 2 800 ml.The patients median survival time was 8.5 months from 3 to 79 months.The prosthesis median survival time was 8 months from 3 to 79 months.According to the Henderson tumor prosthesis complications classification,there were 3 cases of type Ⅰ including 2 cases of incision delayed healing and 1 case of radial nerve paralysis.There was 1 case of type Ⅱ with humeral prosthesis aseptic loosening.There was 1 case of type Ⅲ with angulation deformity between femoral prosthesis force line and biological force line.There were 2 cases of type Ⅴ with tumor recurrence followed by amputation.The limb function score of MSTS was 20.4±4.1 points.Except for two patients with tumor recurrence and amputation,38 patients got stable prosthesis function until the death or follow-up cut-off.The similar tendency of patients survival curve and prosthesis survival curve indicated that survival was the main factor affecting postoperative prosthesis survivorship.Although the use rate of humeral plate (4/8,50.0％) was higher than that of femoral plate (5/28,17.9％),the difference was not statistically significant (F=3.426,P=0.064).The results of statistical analysis of complications showed that the type of tumor was an independent risk factor for complications (x2=7.446,P=0.024).The postoperative complications rate of primary tumor was significantly higher than that of multiple myeloma and bone metastasis.Patients with no complications have better limb function after surgery (F=9.709,P=0.003).Multivariate linear regression analysis showed that age,tumor type,preoperative pathologic fracture,surgery,osteotomy length did not affect limb functions after operation.The longer survival time mean better limb function (t=4.228,P=0.000).Conclusion Segmental prosthesis is a reliable method for the repair of bone metastases with defects.Combined with bone plate fixation,it can effectively reduce the occurrence of prosthetic complications.

A multicenter retrospective study of artificial joint replacement on giant cell tumor in distal femur / 中华骨科杂志

Objective To analyze clinical efficacy of artificial prosthesis in giant cell tumor in distal femur,and to investigate risk factors affecting prosthesis failure and functional outcomes.Methods 42 patients with giant cell tumor of bone in distal femur,who had undergo prosthesis replacement from January 2002 to May 2015,were enrolled in this study.There were 24 males and 18 females,with an average age of 38.53± 12.87 years.There were 28 primary patients and 14 relapsed patients,including 11 cases of recurrence once and 3 cases of twice.Three-dimensional finite element model was used to analyze the effect of different angles of deviation of the spinal needle on the deformation of the bone wall.The correlations between the factors such as age,sex,occupation,prosthesis type,and other factors on prosthesis loosening were compared.Biomechanical effect of lower limbs caused by prosthesis offset angle was analyzed through gait analysis.Analyzed the effects of primary tumor or recurrence,prosthesis service status,and length of surgical osteotomy on joint function.Results A total of 42 patients were followed up by 20-158 months,with an average of 68.7 months.The 3 year survival rate of prosthesis was 83.33％ for 3 years and 57.14％ for 5 years.The major reason of prosthesis failure was loose (18/42,42.8％).X-ray films showed 19 cases of prosthetic intramedullary nail and sagittal bias of medullary force line angle ＞ 3° in the first follow-up.Osteotomy length (OR=0.132,P=0.0027) and offset angle of needle (OR=25.000,P=0.000) were significantly correlated to prosthesis loose.A length more than 12 cm and angle more than 3° were easier to result in prosthesis loose.There were no significant correlation between prosthesis failure and patients age,gender,occupation and prosthesis type.Gait analysis shows that the unsuitable bias angle of the prosthesis can significantly change the joint force of the prosthesis.The average score of MSTS 93 function evaluation was 25.43±4.256,excellent in 33 cases,good in 7 cases and poor in 2 cases.Function of patients with primary GCT were better than that of recurrent ones.Patients with one 1 times recurrence were better than that of recurrence twice (P=0.003).Patients without prosthesis loosening and revision were better than that with loosening (P=0.001).Patients with an osteotomy length less than 12 cm had a poorer function than that with more than 12 cm (P=0.002).Conclusion The main factors affecting distal femoral prosthesis replacement therapy of GCT is loosening,which was caused by broach and medullary cavity mismatch,osteotomy length,prosthesis rotation,prosthesis position.The function of the prosthesis is mainly affected by operation times,prosthesis status,osteotomy length and low patella.

Analysis of risk factors for recurrence of spinal giant cell tumor / 中华骨科杂志

Objective To investigate the factors related to the local recurrence of spine giant cell tumor (GCT) after surgical treatment and provide a reference for the treatment.Methods A retrospective analysis of GCT of the spine from January 2000 to June 2016 was conducted.A total of 73 patients with GCT of the spine who underwent surgical treatment in Giant Cell Tumor Team of China (GTOC) were collected,including 29 males and 44 females.The average age was 33.73±11.34 years (range:13-60 years).Clinical characteristics including gender,age,history of recurrence,tumor position,Ennecking stage,Frankel score,clinical symptoms,surgery procedures,surgical approach,preoperative selective artery embolism (PAE),radiotherapy and bisphosphonate treatment history are collected.The correlation between the factors and tumor recurrence were analyzed by single factor analysis and multiple-factor logistic regression.Results The mean follow-up time was 61.81 ±53.21 months (range:4-210 months).Surgical procedures,bisphosphonate treatment,history of recurrence and radiotherapy were found significant correlation with tumor recurrence by single factor analysis.The result of multiple-factor logistic regression showed that surgical procedures (P=0.026) and bisphosphonate treatment (P=0.017) were independent risk factors for tumor recurrence.Conclusion Total spondylectomy and bisphosphonate treatment could significantly reduce the recurrence rate of GCT of the spine.

The establishment of a decision tree model for the individualized treatment of spinal metastases based on RPA / 中华骨科杂志

Objective To evaluate the prognostic factors of spinal metastases by recursive partitioning analysis (RPA)and establish a decision tree model that can guide clinicians to select individualized treatment.Methods Between January 2011 and December 2015,three institutional databases were searched to identify 169 patients with metastatic spinal tumors underwent surgery.The ratio of male and female was 1.48:1 (102 males and 67 females).The average age was 59.2±11.1 years.One-hundred eighteen cases of patients were randomly selected as training samples and the remaining 51 cases were verified samples.Preoperative factors were collected and analyzed by RPA methods,including primary tumor,KPS score,Frankel grade,gender,age,visceral metastasis,bone metastasis,spinal metastasis,blood glucose,blood pressure,surgery site,symptoms,surgery interval,serum albumin level and other risk factors.Pearson's Chi-square test was performed to judge the segmentation point of the decision tree model.The decision tree model is built using the Chi-square automatic interaction detector (CHIAD) algorithm and sensitivity and specificity was automatically calculated.Results The median postoperative survival time was 12.6±1.2 months [95％CI(10.1,15.0)].70％ were randomly selected as the experimental group (118 cases),and 30％ were the verification group (51 cases).The sensitivity was 96.9％.The specificity was 89.8％.The Kappa coefficient was 0.874 in the experimental group.The sensitivity was 95.4％.The specificity was 90.8％.The Kappa coefficient was 0.810 in the test group.The prognostic factors (weight from high to low) based on RPA were Frankel grade (F=8.132,P=0.005),the primary tumor and the KPS score (Equal,F=9.871,P=0.000 and F=1 1.945,P=0.003),serum albumin and movement time (Equal,F=7.566,P=0.018 and F=9.966,P=0.008).The decision tree model consists of 7 types.Survival time was 51 months,18 months,13 months,8 months,4 months,5 months,9 months in the class Ⅰ～Ⅶ,respectively.According to the difference of RPA survival time,the operation was classified as 3 grade.Total spinal resection was regarded as grade 1,including class Ⅰ and class Ⅱ,with an average survival time of over 18 months.Limited operation was regarded as grade 2,including class Ⅲ,Ⅴ and Ⅶ with survival time in 6-18 months.The conservative treatment was regarded as grade 3,including class Ⅳ and Ⅵ with the survival time was less than 6 months.Conclusion The decision tree model based on RPA for predicting the survival time of spinal metastases can not only identify the prognostic factors,but also classify and grade various prognostic factors;the decision tree model is simple and can guide clinicians to choose the best surgical plan by predicting the survival time.

Outcome of patients with osteosarcoma after recurrence and analysis of factors affecting the long-term survival——A long-term follow-up study of recurrent patients by multicenter / 中华骨科杂志

Objective To investigate the outcome and affecting factors of patients with osteosarcoma after recurrence.Methods Retrospective analysis was used to analyze the achieved data and prognosis-related factors of 72 patients with extremity osteosarcoma after recurrence from June 2000 to September 2012 through multicenter joint treatment.37 males and 35 females were included.The overall age was 7 to 61 years old (average age22.2 years old).Classification based on the tumor recurrent parts:42 cases (58.3％) on femur,18 cases (25％) on tibia,7 cases (9.7％) on humerus and 5 cases (6.9％) on fibula.Classification based on metastases:14 cases of simple recurrence (19.4％),58 cases (80.6％) of recurrence with metastasis:29 cases (40.3％) of recurrence occurred first,9 cases (12.5％) of metastasis occurred firstly,20 cases (27.8％) of simultaneous recurrence with metastasis;12/14 patients (16.7％) of simple recurrence had long-term survival,but 2 died (2.8％).Six of 58 patients (8.3％) of recurrence with metastasis had long-term survival but 52 died (72.2％).Results The overall 10-year postrelapse survival rate of the 72 patients was 25％.Kaplan-Meier univariate analysis revealed that postrelapse survival was significantly influenced by the continued treatment after recurrence and the number of postoperative chemotherapy,but it was not significantlyinfluenced by age,gender and the number of preoperative chemotherapy.Multivariate analysis revealed that the continued treatment after recurrence and the number of postoperative chemotherapy were independent prognostic factors (P=0.002,P=0.007).At the same time,according to the survival curve grouped by different indicators,the number of chemotherapy after recurrence has no significant effect on TFS.However,the continued treatment after recurrence has obvious statistical significance on improving TFS and OS of patients (P=0.026,P=0.002).Conclusion Resection and standard postoperative chemotherapy had significant effects on the postrelapse survival in patients with osteosarcoma.There are good prospects for further multimodal therapy and multicenter cooperation for osteosarcoma after recurrence.