Enhancing rotational placement of reconstruction prostheses of the distal femur after sarcoma resection

Introduction: Currently there are no accepted international guidelines for the correct placement of reconstruction prostheses in the axial plane of the femur after en bloc resection. The most accepted method is based on the linea aspera as an intraoperative landmark, indicating posterior. This study was conducted to address the reliability of the linea aspera as a landmark for rotational alignment. Material and methods: 50 CT angiographies of the right limb were used for this purpose. These 2D images were reconstructed into 3D models using proprietary software (materialize NV, Leuven, Belgium). The posterior condylar line was used as a reference axis. The orientation of the linea aspera was described as the angle between the perpendicular line to the PCL, through the center of the diaphysis, and the lateral (a) and medial labium (beta). Results: The linear mixed model shows that the alpha- and beta-angles are significantly associated with the distance from the joint line (p<0.001) and vary significantly between subjects (p<0.001). The alpha-angle has the lowest variance and approximates more closely true posterior, while the median beta-angle never overlaps true posterior. Discussion: When a surgeon would blindly rely on the linea aspera as a posterior landmark roughly 78% of the femoral implants would exceed the accepted +/- 3 degrees deviation around the surgical transepicondylar axis (sTEA) as defined in total knee replacement. The linea aspera is not a reliable landmark for axial rotation of femoral implants. The position is highly dependent on the osteotomy height and in addition differs between individual patients. Preoperative assessment of the linea aspera is advocated in order to reduce the risk of malrotation. As the height of the osteotomy cannot always be determined correctly preoperatively, a table was designed as a guideline for how much a deviation from the planned resection height will affect the rotation of the implant. (c) 2020 IPEM. Published by Elsevier Ltd. All rights reserved

The in ovo CAM-assay as a xenograft model for sarcoma

Sarcoma is a very rare disease that is heterogeneous in nature, all hampering the development of new therapies. Sarcoma patients are ideal candidates for personalized medicine after stratification, explaining the current interest in developing a reproducible and low-cost xenotransplant model for this disease. The chick chorioallantoic membrane is a natural immunodeficient host capable of sustaining grafted tissues and cells without species-specific restrictions. In addition, it is easily accessed, manipulated and imaged using optical and fluorescence stereomicroscopy. Histology further allows detailed analysis of heterotypic cellular interactions. This protocol describes in detail the in ovo grafting of the chorioallantoic membrane with fresh sarcoma-derived tumor tissues, their single cell suspensions, and permanent and transient fluorescently labeled established sarcoma cell lines (Saos-2 and SW1353). The chick survival rates are up to 75%. The model is used to study graft-(viability, Ki67 proliferation index, necrosis, infiltration) and host (fibroblast infiltration, vascular ingrowth) behavior. For localized grafting of single cell suspensions, ECM gel provides significant advantages over inert containment materials. The Ki67 proliferation index is related to the distance of the cells from the surface of the CAM and the duration of application on the CAM, the latter determining a time frame for the addition of therapeutic products

Expandable distal femur megaprosthesis : a European Musculoskeletal Oncology Society study on 299 cases

Background and Objectives Expandable distal femur prostheses have become more popular over the last decades, but scientific data is limited. Methods A retrospective study was performed, including cases treated between 1986 and 2019 in 15 European referral centers for bone sarcomas. Results A total of 299 cases were included. Average follow-up was 80 months (range, 8-287 months). Mean patient age was 10 years. Most (80%) of the implants were noninvasive growers and a fixed hinge knee was used more often (64%) than a rotating hinge. Most prosthetic designs showed good (>80%) implant survival at 10 years, but repeat surgery was required for 63% of the patients. The most frequent reason for revision procedure was the completion of lengthening potential. Noninvasive expandable implants showed less risk of infection compared to invasive growers (11.8% vs 22.9% at 10 years). No difference in aseptic loosening was found between cemented and uncemented stems. Conclusions This study shows the increasing popularity of expandable distal femur prostheses, with overall good results for function and implant survival. However, repeat surgery is frequently required, especially in patients under the age of 10 years old. Infection is less frequent in noninvasive growers compared to implants that require invasive lengthening procedures

MISpheroID: a knowledgebase and transparency tool for minimum information in spheroid identity

Spheroids are three-dimensional cellular models with widespread basic and translational application across academia and industry. However, methodological transparency and guidelines for spheroid research have not yet been established. The MISpheroID Consortium developed a crowdsourcing knowledgebase that assembles the experimental parameters of 3,058 published spheroid-related experiments. Interrogation of this knowledgebase identified heterogeneity in the methodological setup of spheroids. Empirical evaluation and interlaboratory validation of selected variations in spheroid methodology revealed diverse impacts on spheroid metrics. To facilitate interpretation, stimulate transparency and increase awareness, the Consortium defines the MISpheroID string, a minimum set of experimental parameters required to report spheroid research. Thus, MISpheroID combines a valuable resource and a tool for three-dimensional cellular models to mine experimental parameters and to improve reproducibility. © 2021, The Author(s)

Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement

Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and bio-banking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientifc progress, promote collaboration, and improve outcomes