Novel candidate metastasis-associated genes for synovial sarcoma.

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with poor prognosis due to late recurrence and metastasis. Metastasis is an important prognostic factor of SS. This study aimed to identify the core genes and mechanisms associated with SS metastasis. Microarray data for GSE40021 and GSE40018 were obtained from the Gene Expression Omnibus database. 186 differentially expressed genes (DEGs) were identified. The biological functions and signalling pathways closely associated with SS metastasis included extracellular matrix (ECM) organization and ECM-receptor interaction. Gene set enrichment analysis showed that the terms cell cycle, DNA replication, homologous recombination and mismatch repair were significantly enriched in the metastasis group. Weighted gene co-expression network analysis identified the most relevant module and 133 hub genes, and 31 crossover genes were identified by combining DEGs. Subsequently, four characteristic genes, EXO1, NCAPG, POLQ and UHRF1, were identified as potential biomarkers associated with SS metastasis using the least absolute shrinkage and selection operator algorithm and validation dataset verification analysis. Immunohistochemistry results from our cohort of 49 patients revealed visible differences in the expression of characteristic genes between the non-metastatic and metastatic groups. Survival analysis indicated that high expression of characteristic genes predicted poor prognosis. Our data revealed that primary SS samples from patients who developed metastasis showed activated homologous recombination and mismatch repair compared to samples from patients without metastasis. Furthermore, EXO1, NCAPG, POLQ and UHRF1 were identified as potential candidate metastasis-associated genes. This study provides further research insights and helps explore the mechanisms of SS metastasis.

Efficacy and safety of a 3D-printed arthrodesis prosthesis for reconstruction after resection of the proximal humerus: preliminary outcomes with a minimum 2-year follow-up.

BACKGROUND: The purpose of this study was to investigate the feasibility of using a three-dimensional (3D)-printed arthrodesis prosthesis for reconstruction of the proximal humeral defect after tumor resection. METHODS: A novel proximal humeral prosthesis was designed to restore bone continuity and shoulder arthrodesis and was fabricated via 3D printing technology. Ten patients with primary malignancies in the proximal humerus underwent intra-articular resection and replacement with this prosthesis from 2017 to 2019. Baseline and operative data, oncological and prosthetic survival, and functional status were summarized. RESULTS: This cohort consisted of 9 males and 1 female with a mean age of 32.1 ± 16.1 years. Diagnoses included 5 cases of osteosarcoma, 3 cases of chondrosarcoma and 1 each case of undifferentiated pleomorphic sarcoma and malignant myoepithelioma. The mean operative duration, intraoperative hemorrhage and postoperative length of hospitalization were 151.5 ± 61.0 min, 410.0 ± 353.4 ml and 5.3 ± 1.9 d, respectively. The mean follow-up duration was 29.3 ± 6.4 months, with a minimum of 24 months for the surviving patients. Two patients experienced local recurrence, and four patients developed distant metastases. Detachment of the taper occurred in two patients. One was managed conservatively, and the other received amputation due to concurrent tumor recurrence. The mean MSTS-93 and ASES scores and ranges of forwards flexion and abduction were 24.9 ± 3.1, 79.4 ± 8.3, 71.3 ± 19.4°, and 61.3 ± 16.4°, respectively. The functional outcomes were independent of the preservation of the axillary nerve. Histological study of the glenoid component showed evidence of bone ingrowth at the bone-prosthesis porous interface. CONCLUSION: Application of the 3D-printed arthrodesis prosthesis might be a safe and efficacious method for functional reconstruction in patients who underwent resection of the proximal humerus, especially for those without preservation of the axillary nerve.

Differences in clinical characteristics and tumor prognosis between primary and secondary conventional pelvic chondrosarcoma.

BACKGROUND: Chondrosarcoma (CS) most commonly involves the pelvis. This study aimed to analyze differences in clinical characteristics and prognostic factors between primary and secondary conventional pelvic CS, and provide reference for clinical diagnosis and treatment. METHODS: Eighty patients (54 primary cases and 26 secondary cases) with pelvic CS were included in this retrospective study. The tumor site, Enneking stage, soft tissue mass, margin, initial tumor grade, incidence of local recurrence and distant metastasis were evaluated. Kaplan-Meier method was used to calculate the overall survival rate. X2 test and log-rank test were used for univariate analysis, and Cox test was used in multivariate analysis. RESULTS: The average age of patients with secondary CS was significantly younger than that of patients with primary CS (P < 0.001). The soft tissue mass of patients with secondary CS was significantly larger than that of patients with primary CS (P = 0.002). There was a significant difference in initial tumor pathologic grade between the two groups (P = 0.002). No statistically significant difference was observed in the local recurrence rate between the two groups. The median recurrence time of patients with primary CS after the first treatment was significantly shorter than that of patients with secondary CS (P < 0.001). The overall survival rate of patients with secondary CS was much higher than that of patients with primary CS (P = 0.003). Cox regression analysis showed that the initial tumor grade was an independent factor in the overall survival rate of patients with CS. CONCLUSION: There were significant differences in age, soft tissue mass, initial tumor grade, and overall survival rate between the two groups. The overall survival rate of pelvic CS was related to the initial tumor grade of CS.

Prognosis and risk factors for malignant peripheral nerve sheath tumor: a systematic review and meta-analysis.

BACKGROUND: No available meta-analysis was printed to systematically introduce the MPNST clinic outcome and risk factors based on largely pooled data. This systematic review and meta-analysis aimed to investigate 5-year OS rate, 5-year EFS rate, and LR rate for MPNST, and to assess potential risk factors for prognosis. METHODS: Electronic articles published between January 1, 1966 and February 29, 2020 were searched and critically evaluated. The authors independently reviewed the abstracts and extracted data for 5-year OS rate, 5-year EFS rate, LR rate, and potential risk factors for prognosis. RESULTS: Twenty-eight literatures were finally included for meta-analysis. The pooled 5-year OS rate, 5-year EFS rate, and LR rate were 49%, 37%, and 38%, respectively. The significant prognostic factors for survival were NF1 status, tumor size, depth, location, malignant grade, margin status, chemotherapy, and radiotherapy. Age and sex were not associated with survival. CONCLUSION: Survival and local recurrence of MPNST are poor. Worse prognosis is mainly associated with NF 1, large size, deep to fascia, high grade, metastases, and location (trunk and head and neck). Complete resection with adequate surgical margins is the mainstay protective factor of MPNST patients, following necessary adjuvant therapies.

Is a Modular Pedicle-hemipelvic Endoprosthesis Durable at Short Term in Patients Undergoing Enneking Type I + II Tumor Resections With or Without Sacroiliac Involvement?

BACKGROUND: Functional reconstruction after Enneking Type I + II resections of the pelvis (those involving both the ilium and the acetabulum) is challenging, especially if resection of part of the sacrum is included. To assess the clinical outcomes of a newly designed modular pedicle-hemipelvic endoprosthesis, we performed a preliminary retrospective study on its clinical use in a small group of patients. QUESTIONS/PURPOSES: The purposes of this study were (1) to evaluate in a small case series whether the new endoprosthesis restored lower limb function and lumbopelvic stability in the short term; (2) to identify the complications associated with use of the new prosthesis; and (3) to assess the 5-year cumulative survival, the cumulative incidence of a major postoperative event, and the cumulative incidence of implant failure in this group of patients. METHODS: Between August 2012 and August 2014, our center performed 274 internal hemipelvectomies for oncologic indications. Among these, 20 were treated with the new endoprosthesis, which was designed for fixation both to the residual sacrum as well as the lumbar spine. An earlier version of the device had been removed from the market because of an unacceptable risk of serious complications. All of the 20 tumors were sarcomas necessitating en bloc resection. The implant is modular and can meet the different-sized defects in each patient. The general indication for use of the new implant was a total acetabular defect with extensive iliac involvement or total loss of the sacroiliac joint and/or hemisacrum. All 20 patients were followed up for a minimum of 24 months or until death in those patients who survived < 2 years (median, 36 months; range, 6-60 months). The clinical data were retrieved from the database and the study endpoints (function according to the Musculoskeletal Tumor Society [MSTS] score, complications, and survivorship of patients and implants) were ascertained by chart review. Lumbopelvic stability was defined as an excellent or good rating according to the International Society of Limb Salvage radiologic implant evaluation system. The cumulative survival of patients was estimated using the Kaplan-Meier approach. The cumulative incidence of major postoperative events including local recurrence, metastasis, and reoperation was estimated using a competing events analysis; the cumulative incidence of implant failure, including mechanical failure or deep infection, in patients who underwent reoperation was also estimated using a competing events analysis. RESULTS: In the 16 patients who survived > 12 months, the median MSTS score was 19 of 30 (range, 5-26). Radiographic assessments demonstrated lumbopelvic stability in all of the 16 patients. Twelve of 20 patients developed postoperative complications, primarily including deep infection (one), hip dislocation (two), and local recurrence (three). Major revision surgery was performed in five of 20 patients. The estimated 5-year Kaplan-Meier patient survival rate was 69% (95% confidence interval [CI], 59%-79%), whereas the cumulative incidence of major postoperative events and implant failure using the competing risk estimator was 42% (95% CI, 23%-60%) and 15% (95% CI, 4%-34%) at 5 years, respectively. CONCLUSIONS: Preliminary results with hemipelvic reconstruction using this new endoprosthesis achieved fair functional results and the complications that were observed appeared comparable to other reconstruction options at short-term followup. Longer-term surveillance is called for to see whether this implant will be durable compared with other available reconstructive alternatives such as a custom-made megaendoprosthesis or an autograft/allograft-prosthetic composite. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Comparison between uncemented and cemented fixation for the tibial component in distal femoral replacement: a clinical and radiological study.

PURPOSES: We performed a retrospective, cohort study to compare uncemented tibial fixation with cemented tibial fixation in distal femoral replacement (DFR). METHODS: Sixty-two cases with uncemented tibial fixation and 58 cases with cemented tibial fixation were included. Inter-group comparisons were performed for baseline data, oncological and prosthetic outcomes, and changes of cortical thickness of tibial diaphysis. Radiological signs of bone adaptations around the uncemented tibial stem were identified through evaluation of plain films during follow-up. RESULTS: Uncemented tibial fixation shortened operative duration by 26 minutes, achieved equivalent oncological and prosthetic outcomes, and helped preserve anterior cortical thickness of tibia compared with the cemented counterpart after a mean follow-up of over 40 months. Radiological signs of osseointegration and reactive line were observed in 64.3 and 17.9% cases with uncemented tibial fixation. The two signs had different patterns of distribution and no significant predisposing factors could be identified. CONCLUSIONS: For DFR, the uncemented tibial fixation was safe and effective in functional reconstruction and in preservation of anterior cortex of tibial diaphysis. It could achieve osseointegration and might permit adaptive micromotion of the tibial stem post-operatively. LEVEL OF EVIDENCE: level III Therapeutic.

One-step reconstruction with a 3D-printed, custom-made prosthesis after total en bloc sacrectomy: a technical note.

BACKGROUND: Surgeries for primary malignancies involving upper sacrum require total en bloc sacrectomy followed by complex mechanical reconstruction, which might be simplified by application of the three-dimensional (3D) printing technique. PURPOSES: To describe the design of a 3D-printed custom-made prosthesis for reconstruction after total en bloc sacrectomy, the surgical technique, and the clinical and functional outcome of a patient. METHODS: A 62-year-old patient with recurrent sacral chordoma was admitted in our center. One-stage total en bloc sacrectomy through posterior approach was planned, and a 3D-printed sacral prosthesis was prepared for reconstruction according to the anticipated osteotomic planes. RESULTS: The patient received one-stage total en bloc sacrectomy through posterior approach followed by reconstruction with the 3D-printed sacral prosthesis. The whole procedure took 5 h, and intra-operative blood loss was 3400 ml. The patient recovered uneventfully and started ambulation at 3 weeks after surgery. An asymptomatic instrument failure was found radiographically at 8-month follow-up. At 1 year after surgery, the patient was disease free and could walk over short distance with crutches without pain or any mechanical instability. CONCLUSIONS: The advantages of our reconstruction method included: (1) the prosthesis provided an optimal reconstruction of lumbosacral and pelvic ring by integrating spinal pelvic fixation, posterior pelvic ring fixation, and anterior spinal column fixation in one step and (2) its porous surface could induce bone ingrowth and might enhance stability. Although there was an instrumental failure, we considered that it could be one reconstructive option. More research is warranted focusing on the modification of locations, diameters, and quantity of screws and biomechanical characteristics. The long-term functional and bone in-growth outcome will be followed to validate the use of the prosthesis.

Lateral lumbar vertebral body screw predisposes to neuralgia after limb-salvage surgery for pelvic tumors: a single-center, retrospective study of 349 cases.

PURPOSE: To investigate the incidence and risk factors of neuralgia after limb-salvage surgery for pelvic tumors with focus on the reconstruction methods. METHODS: We included 349 cases of pelvic tumors treated with internal hemipelvectomy and reconstruction in our center from January 2009 to May 2015. None of these cases had major lumbosacral nerves invaded by the tumors. Demographic and medical data were reviewed and documented for statistical analyses. The locations of lateral lumbar vertebral body screws (LLVBSs) were evaluated in 26 cases. RESULTS: The overall incidence of post-operative neuralgia was 8.3 %. Pre-admission requirement of analgesics (OR 4.089; 95 % CI 1.711-9.774) and application of LLVBS (OR 11.848; 95 % CI 4.369-32.129) were independent risk factors of neuralgia. The horizontal location of LLVBS did not affect the incidence of neuralgia when it was placed near the midline of the vertebra. CONCLUSIONS: The incidence of post-operative neuralgia was 8.3 % in this study cohort. The LLVBS technique could increase the risk of post-operative neuralgia.

Fluoroscopically calibrated 3D-printed patient-specific instruments improve the accuracy of osteotomy during bone tumor resection adjacent to joints.

BACKGROUND: Inadequate surface matching, variation in the guide design, and soft tissue on the skeletal surface may make it difficult to accurately place the 3D-printed patient-specific instrument (PSI) exactly to the designated site, leading to decreased accuracy, or even errors. Consequently, we developed a novel 3D-printed PSI with fluoroscopy-guided positioning markers to enhance the accuracy of osteotomies in joint-preserving surgery. The current study was to compare whether the fluoroscopically calibrated PSI (FCPSI) can achieve better accuracy compared with freehand resection and conventional PSI (CPSI) resection. METHODS: Simulated joint-preserving surgery was conducted using nine synthetic left knee bone models. Osteotomies adjacent to the knee joint were designed to evaluate the accuracy at the epiphysis side. The experiment was divided into three groups: free-hand, conventional PSI (CPSI), and fluoroscopically Calibrated PSI (FCPSI). Post-resection CT scans were quantitatively analyzed. Analysis of variance (ANOVA) was used. RESULT: FCPSI improved the resection accuracy significantly. The mean location accuracy is 2.66 mm for FCPSI compared to 6.36 mm (P < 0.001) for freehand resection and 4.58 mm (P = 0.012) for CPSI. The mean average distance is 1.27 mm compared to 2.99 mm (p < 0.001) and 2.11 mm (p = 0.049). The mean absolute angle is 2.16° compared to 8.50° (p < 0.001) and 5.54° (p = 0.021). The mean depth angle is 1.41° compared to 8.10° (p < 0.001) and 5.32° (p = 0.012). However, there were no significant differences in the front angle compared to the freehand resection group (P = 0.055) and CPSI (P = 0.599) group. The location accuracy observed with FCPSI was maintained at 4 mm, while CPSI and freehand resection exhibited a maximum deviation of 8 mm. CONCLUSION: The fluoroscopically calibrated 3D-printed patient-specific instruments improve the accuracy of osteotomy during bone tumor resection adjacent to joint joints compared to conventional PSI and freehand resection. In conclusion, this novel 3D-printed PSI offers significant accuracy improvement in joint preserving surgery with a minimal increase in time and design costs.

Clinical outcomes in patients with neurological disorders following periacetabular tumor removal and endoprosthetic reconstruction of the hemipelvis.

Background: Surgical treatment of musculoskeletal tumors in the periacetabular region present extremely difficult due to the complex anatomy and need for reconstruction. Orthopedic surgeons face more difficulties in patients with neurological conditions, which can cause increased muscle tone, an elevated risk of fractures, and compromised bone quality. There is limited evidence regarding endoprosthetic reconstruction for periacetabular tumors in individuals with neurological disorders. Methods: We conducted a single-center retrospective study to examine the outcomes of patients with preexisting neurological conditions who underwent surgery to remove periacetabular tumors and who underwent endoprosthesis reconstruction. Clinical presentation, detailed neurological conditions, complications, and functional outcomes were studied. Results: Sixteen out of the 838 patients were identified (1.91%), with a mean follow-up time of 33 months. The primary neurological conditions encompassed Parkinson's disease, Alzheimer's disease, dementia, and cerebral ischemic stroke. Every patient was diagnosed with periacetabular lesions that were either primary or oligometastatic. They underwent tumor resection and subsequently received endoprosthetic reconstruction of the hemipelvis. Three patients developed metastasis lesions later, and two patients experienced tumor recurrence. Five cases experienced hip dislocation-one with periprosthetic fracture and one with surgical site infection. The position of the prosthetic rotating center was not correlated with dislocation. The reoperation rate was 31.25%. The cohort of patients all presented with more extended hospital stays and rehabilitation. In 3 patients, the general functional score was good, while in 6 patients, it was fair; in 7 patients, it was regarded as poor. The average MSTS93 score was 49.71%. Conclusion: Endoprosthetic reconstruction after periacetabular tumor resection is an effective way to eliminate tumors and salvage limbs. However, this group of patients has an increased likelihood of secondary surgery, complications, extended hospital stay, and no significant improvement in functional outcomes. Despite the diverse nature of the cohort, it is recommended to consider enhanced soft tissue reconstruction, supervised functional recovery and rehabilitation training.

Artificial intelligence assisted preoperative planning and 3D-printing guiding frame for percutaneous screw reconstruction in periacetabular metastatic cancer patients.

Background: The percutaneous screw reconstruction technique, known as the "Tripod Technique," has demonstrated favorable clinical outcomes in the management of metastatic periacetabular lesions, as evidenced by our prior investigations and corroborated by independent studies. Nevertheless, there is a steep learning curve in handling this technique, with possible complications such as intraarticular screw placement. Methods: Preoperative pelvic CT scans were acquired before surgery and utilized for the guiding frame design. A convolutional neural network model was trained with annotated data to identify the starting point and trajectory of each potential screw. A model boundary intersection detection technology was used to determine the optimal diameter and length of each screw. A non-rigid registration technology was matched with a prefabricated model of the body surface to design personalized anchoring skin pads. Finally, a polylactic acid-based guiding frame for intraoperative was custom-made with a 3D printer. Results: 12 patients underwent a guiding frame-assisted Tripod procedure for treatment of periacetabular metastatic lesions. An intraoperative CT scan was performed in all cases to confirm screw trajectories. Among 36 screws that were implanted, 26 screws were implanted as designed. The remaining ten screws drifted, but all remained within the intra-osseous conduit without any complications. The mean surgical time was 1.22 h with the guiding frame compared with 2.3 h without the guiding frame. Following the surgical procedure, a noteworthy enhancement in pain management, as evidenced by a reduction in scores on the visual analog scale (p < 0.01), and an improvement in functional status, as assessed through the Eastern Cooperative Oncology Group score (p < 0.01), were observed when compared to the patient's pre-operative condition. Conclusion: This proof-of-concept investigation demonstrates that the amalgamation of AI-assisted surgical planning and additive manufacturing can improve surgical accuracy and shorten surgical duration. While access to this technology is currently constrained during its early stages of development, it is anticipated that these limitations will diminish as the potential of AI and additive manufacturing in facilitating complex orthopedic procedures becomes more evident, leading to a surge in interest and adoption of this approach.

Outcomes of Semiknee Replacement in Skeletally Immature Bone Sarcoma Patients.

INTRODUCTION: A semiknee mega endoprosthesis (SKMEP) was used to replace the resected distal femur or proximal tibia in skeletally immature bone sarcoma patients. This study investigated the surgical technique, endoprosthesis survival rate, functional outcome, complications, and approaches to resolve limb-length discrepancy (LLD) following this procedure. PATIENTS AND METHODS: In total, 15 girls and 16 boys with a mean age of 9.1 years (range, 4-12) and 8.9 years (range, 5-13), respectively, were included in this study. The mean length of the resected distal femur (15 cases) and proximal tibia (16) was 145.0 and 122.8 mm, respectively. Altogether, 19 custom-made SKMEPs and 12 modular units were used to reconstruct the bone and joint defects. RESULTS: The average follow-up was 82.8 months (range, 4-225 months). Five patients died of disease. Seven SKMEPs were revised to total knee endoprosthesis after a mean of 40.3 months. Nineteen patients retained the original SKMEP, and the mean LLD was 4.3 cm (range, 0-10 cm). One case each of Henderson type 1B, type 2A, type 2B, and type 5B failures was observed. Knee subluxation occurred in two cases. Although a slight laxity of the knee was identified on physical examination, the average Musculoskeletal Tumor Society 93(MSTS93) functional score was 84.5% (range, 57-97%). The estimated implant survival was 70.5% at 5 years. CONCLUSION: This was the largest retrospective study reporting the application of SKMEP in bone sarcoma patients. For selected skeletally immature bone sarcoma patients, SKMEP is an option with satisfactory functional outcomes and survival rates. However, heightening pads or shoes to compensate the LLD were indispensable before subsequent LLD was adjusted by further operation(s).

Integrated analysis of single-cell and bulk RNA sequencing data reveals an immunostimulatory microenvironment in tumor thrombus of osteosarcoma.

Tumor thrombus of bone sarcomas represents a unique reservoir for various types of cancer and immune cells, however, the investigation of tumor thrombus at a single-cell level is very limited. And it is still an open question to identify the thrombus-specific tumor microenvironment that is associated with the tumor-adaptive immune response. Here, by analyzing bulk tissue and single-cell level transcriptome from the paired thrombus and primary tumor samples of osteosarcoma (OS) patients, we define the immunostimulatory microenvironment in tumor thrombus of OS with a higher proportion of tumor-associated macrophages with M1-like states (TAM-M1) and TAM-M1 with high expression of CCL4. OS tumor thrombus is found to have upregulated IFN-γ and TGF-ß signalings that are related to immune surveillance of circulating tumor cells in blood circulation. Further multiplexed immunofluorescence staining of the CD3/CD4/CD8A/CD68/CCL4 markers validates the immune-activated state in the tumor thrombus samples. Our study first reports the transcriptome differences at a single-cell level between tumor thrombus and primary tumor in sarcoma.

Hypertriglyceridemia: A Neglected Risk Factor for Ischemic Stroke?

Hypertriglyceridemia is caused by defects in triglyceride metabolism and generally manifests as abnormally high plasma triglyceride levels. Although the role of hypertriglyceridemia may not draw as much attention as that of plasma cholesterol in stroke, plasma triglycerides, especially nonfasting triglycerides, are thought to be correlated with the risk of ischemic stroke. Hypertriglyceridemia may increase the risk of ischemic stroke by promoting atherosclerosis and thrombosis and increasing blood viscosity. Moreover, hypertriglyceridemia may have some protective effects in patients who have already suffered a stroke via unclear mechanisms. Therefore, further studies are needed to elucidate the role of hypertriglyceridemia in the development and prognosis of ischemic stroke.

Elbow hemiarthroplasty with a 3D-printed megaprosthesis for defects of the distal humerus or proximal ulna after tumour resection : a preliminary report.

AIMS: The aim of this study was to investigate the feasibility of application of a 3D-printed megaprosthesis with hemiarthroplasty design for defects of the distal humerus or proximal ulna following tumour resection. METHODS: From June 2018 to January 2020, 13 patients with aggressive or malignant tumours involving the distal humerus (n = 8) or proximal ulna (n = 5) were treated by en bloc resection and reconstruction with a 3D-printed megaprosthesis with hemiarthroplasty, designed in our centre. In this paper, we summarize the baseline and operative data, oncological outcome, complication profiles, and functional status of these patients. RESULTS: Preparation of the prosthesis was a mean of 8.0 days (SD 1.5), during which time no patients experienced tumour progression. The mean operating time and intraoperative blood loss were 158.1 minutes (SD 67.6) and 176.9 ml (SD 187.8), respectively. All of the prostheses were implanted successfully. During a mean follow-up of 25.7 months (SD 7.8), no patients died, but four had complications (two superficial wound problems, one temporary palsy of radial nerve, and one dislocation). No aseptic loosening, structural failure, infection, heterotopic ossification, or degenerative arthritis was seen in this study. The mean flexion of the elbow was 119.6° (SD 15.9°) and the mean extension lag was 11.9° (SD 13.8°). The mean Musculoskeletal Tumor Society 93 score and Mayo Elbow Performance Score were 28.4 (SD 0.9) and 97.7 (SD 4.4), respectively. CONCLUSION: The custom-made, 3D-printed megaprosthesis with hemiarthroplasty is a feasible option for functional reconstruction after resection of a tumour in the distal humerus or proximal ulna. Cite this article: Bone Joint J 2022;104-B(6):747-757.

Reconstruction With a 3D-Printed Megaprosthesis With Ankle Arthrodesis After Distal Tibial Tumor Resection.

BACKGROUND: Reconstruction after en bloc resection of the distal tibia has remained an unsettled issue despite many attempts with bone grafts or prostheses in the past. Failures of the previous methods have been attributed to inadequate mechanical strength, poor articular stability, failed osseointegration, and poor soft tissue coverage. To overcome these shortcomings, we designed and applied a 3D-printed megaprosthesis with ankle arthrodesis. METHODS: A total of 13 patients underwent resection of a distal tibial tumor and reconstruction with a 3D-printed distal tibial megaprosthesis between January 2017 and November 2020. Mean age was 14.9±6.5 years. Diagnoses included 11 cases of osteosarcoma and 1 case each of low-grade phosphaturic mesenchymal tumor and rhabdomyosarcoma. Baseline characteristics, operative data, complication profiles, and oncologic, and functional outcomes were reviewed and analyzed. RESULTS: All 13 cases attained a wide or marginal resection. During a mean follow-up of 26.8±10.6 months, 1 patient experienced local recurrence and distant metastasis, whereas 3 other patients only developed distant metastasis. Periprosthetic infection subsequent to paronychia occurred in 1 patient 24 months after the operation. No other complications were observed. By the last follow-up, the mean MSTS-93 score was 28.0±1.5. CONCLUSION: In this relatively small cohort with short-term follow-up, reconstruction with the 3D-printed megaprosthesis with ankle arthrodesis was found to be a safe and efficacious method after resection of a distal tibial malignancy.

Ultra-Short Course of Neo-Adjuvant Denosumab for Nerve-Sparing Surgery for Giant Cell Tumor of Bone in Sacrum.

STUDY DEIGN: This was a retrospective study about sacral giant cell tumor of bone (GCTB). OBJECTIVE: This study aimed to investigate whether ultra-short course of neo-adjuvant denosumab treatment for sacral GCTB could (1) induce radiological and histological response? (2) Facilitate nerve-sparing surgery? (3) Achieve satisfactory oncological and functional outcomes? SUMMARY OF BACKGROUND DATA: Previous reports on long course of neo-adjuvant denosumab treatment for GCTB showed significant tumor response and a relatively high recurrent rate after curettage. METHODS: Sixty-six patients with sacral GCTB treated with neoadjuvant denosumab and nerve-sparing surgery were categorized into ultra-short course group (≤3 doses and operation within D21 since 1st dose, 41 patients) or conventional group (>3 doses or operation after D21 since 1st dose, 25 patients). The radiological and histological response, operative data, oncological and functional outcomes were compared. RESULTS: The ultra-short course group demonstrated fewer doses of neo-adjuvant denosumab (mean: 2.1 vs. 4.8, P  < 0.001) and shorter time to surgery (12.2 days vs. 72.3 days, P < 0.001). Similar patterns of radiological and histological response were observed in the two groups with less fibrosis and ossification in the ultra-short course group. The operative duration (199.9 min vs. 187.8 min, P = 0.364) and estimated blood loss (1552.4 mL vs. 1474.0 mL, P = 0.740) were comparable. Most (94.8%) of the patients received adjuvant denosumab. After a mean follow-up of 29.4 months, three cases (8.8%) and five cases (20.8%) showed local recurrence in each group (P = 0.255). The estimated recurrence-free survival (56.2 vs. 51.2 months, P = 0.210) and the functional status [Motor-Urination-Defecation scores: 25.9 vs. 25.7, P = 0.762] did not differ between the two groups. CONCLUSION: Ultra-short course of neo-adjuvant denosumab for sacral GCTB could elicit radiological and histological responses as conventional course did. The less degree of fibrosis and ossification might facilitate nerve-sparing surgery and help to achieve satisfactory local control and functional status.Level of Evidence: 4.

Venous Tumor Thrombus in Primary Bone Sarcomas in the Pelvis: A Clinical and Radiographic Study of 451 Cases.

BACKGROUND: Few investigations of venous tumor thrombus (VTT) in primary pelvic bone sarcomas are available. We aimed to identify the prevalence, associated factors, and prognosis of VTT across different types of pelvic sarcomas and to propose an algorithm for management. METHODS: We included 451 consecutive cases of primary, bone-derived, treatment-naive, pelvic sarcomas in this study. Demographic data and the results of initial laboratory tests, imaging examinations, and oncological evaluations were extracted and analyzed. Forty-four cases of VTT were diagnosed with radiographic examinations, and 18 of them were verified histologically. RESULTS: The cohort consisted of chondrosarcomas (41.2%), osteosarcomas (30.4%), Ewing sarcomas (15.5%), bone-derived undifferentiated pleomorphic sarcomas (5.8%), and other bone sarcomas (7.1%). The prevalence of VTT was 9.8% in the whole group, and associated factors included a lactate dehydrogenase (LDH) level of ≥230.5 U/L and invasion of the L5-S1 intervertebral foramen. Patients with pelvic osteosarcoma had a high prevalence of VTT (22.6%), and the associated factors in this group included a chondroblastic subtype, an LDH level of ≥187 U/L, and invasion of the obturator foramen and the L5-S1 intervertebral foramen. Patients with VTT had a poor prognosis with a median overall survival time of 14 months. Subgroup analyses of localized pelvic osteosarcoma indicated that the presence of VTT decreased the median overall survival time (21.5 versus 54.0 months for those without VTT, p = 0.003), median recurrence-free survival time (18.6 versus 32.4 months, p = 0.020), and median metastasis-free survival time (11.2 versus 41.0 months, p < 0.001). CONCLUSIONS: VTT is most common in patients with pelvic osteosarcoma as compared with patients with other primary bone sarcomas, and it is associated with several factors. It is a negative prognostic factor. An algorithm for management of pelvic sarcomas with VTT stratified by the classification of the VTT might be beneficial, but further validation is necessary. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

3D-Printed Modular Hemipelvic Endoprosthetic Reconstruction Following Periacetabular Tumor Resection: Early Results of 80 Consecutive Cases.

BACKGROUND: Reconstruction with an endoprosthesis following pelvic tumor resection has increased over the years. However, the long-term results reflect a disappointing frequency of mechanical complications and failures. In an attempt to enhance implant fixation, an electron beam melting (EBM)-based modular hemipelvic endoprosthesis was introduced. Our aim was to explore the preliminary clinical outcomes for patients who have been managed with this prosthesis. METHODS: We reviewed the records of 80 consecutive patients who had been managed at a single center between June 2015 and September 2017. Chondrosarcoma was the predominant diagnosis (31.3%). Osseous metastases were diagnosed in 16 patients (20.0%). The position of the reconstructed metallic acetabulum was measured on an anteroposterior pelvic radiograph. Bone ingrowth was evaluated in 2 samples harvested from patients with tumor recurrence. RESULTS: After a median duration of follow-up of 32.5 months (range, 9 to 52 months), no acetabular component instability was detected on radiographs. Histological sectioning of specimens harvested from 2 patients with tumor recurrence showed bone trabeculae extending toward the implant and bone ingrowth within the porous network. At the time of the latest follow-up, 59 patients (73.8%) were alive with no evidence of disease, 5 patients (6.3%) were alive with disease, and 16 patients (20.0%) had died of disease. Local recurrence occurred in 9 patients (11.3%). The mean Musculoskeletal Tumor Society score at the time of the latest follow-up was 83.9% (range, 43% to 100%). Complications occurred in 16 patients (20%), with wound dehiscence being the most common complication (8 patients; 10%). No aseptic loosening was found. Five patients (6.3%) had deep infection, and 2 patients (2.5%) had dislocation. CONCLUSIONS: The use of a 3-dimensional (3D)-printed modular hemipelvic endoprosthesis with a highly porous metal interface represents a potential choice as a pelvic endoprosthesis after internal hemipelvectomy for the treatment of a primary or metastatic tumor. These preliminary results demonstrate stable fixation with acceptable early functional and radiographic outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Retrospective cohort study of 68 sacral giant cell tumours treated with nerve-sparing surgery and evaluation on therapeutic benefits of denosumab therapy.

AIMS: To investigate the benefits of denosumab in combination with nerve-sparing surgery for treatment of sacral giant cell tumours (GCTs). METHODS: This is a retrospective cohort study of patients with GCT who presented between January 2011 and July 2017. Intralesional curettage was performed and patients treated from 2015 to 2017 also received denosumab therapy. The patients were divided into three groups: Cohort 1: control group (n = 36); cohort 2: adjuvant denosumab group (n = 9); and cohort 3: neo- and adjuvant-denosumab group (n = 17). RESULTS: There were 68 patients within the study period. Six patients were lost to follow-up. The mean follow-up was 47.7 months (SD 23.2). Preoperative denosumab was found to reduce intraoperative haemorrhage and was associated with shorter operating time for tumour volume > 200 cm3. A total of 17 patients (27.4%) developed local recurrence. The locoregional control rate was 77.8% (7/9) and 87.5% (14/16) respectively for cohorts 2 and 3, in comparison to 66.7% (24/36) of the control group. The recurrence-free survival (RFS) rate was significantly higher for adjuvant denosumab group versus those without adjuvant denosumab during the first two years: 100% vs 83.8% at one year and 95.0% vs 70.3% at two years. No significant difference was found for the three-year RFS rate. CONCLUSION: Preoperative denosumab therapy was found to reduce intraoperative haemorrhage and was associated with shorter operating times. Adjuvant denosumab was useful to prevent early recurrence during the first two years after surgery. Cite this article: Bone Joint J 2020;102-B(2):177-185.