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Chordoma is a rare primary bone malignancy that arises in the skull base, spine and sacrum and originates from remnants of the notochord. These tumors are typically resistant to conventional chemotherapy, and to date there are no FDA-approved agents to treat chordoma. The lack of in vivo models of chordoma has impeded the development of new therapies for this tumor. Primary tumor from a sacral chordoma was xenografted into NOD/SCID/IL-2R γ-null mice. The xenograft is serially transplantable and was characterized by both gene expression analysis and whole genome SNP genotyping. The NIH Chemical Genomics Center performed high-throughput screening of 2,816 compounds using two established chordoma cell lines, U-CH1 and U-CH2B. The screen yielded several compounds that showed activity and two, sunitinib and bortezomib, were tested in the xenograft. Both agents slowed the growth of the xenograft tumor. Sensitivity to an inhibitor of IκB, as well as inhibition of an NF-κB gene expression signature demonstrated the importance of NF-κB signaling for chordoma growth. This serially transplantable chordoma xenograft is thus a practical model to study chordomas and perform in vivo preclinical drug testing. [ABSTRACT FROM AUTHOR]

Background and Objective: Thymectomy as a management strategy for juvenile myasthenia gravis (JMG) has been increasingly adopted with the advent of minimally invasive surgical techniques. This review evaluates existing evidence regarding the surgical management of JMG, including the benefits of surgical compared to medical therapy, important considerations when evaluating surgical candidacy and determining optimal timing of intervention. In addition, we provide an overview of the open, thoracoscopic and robotic surgical approaches available for thymectomy and compare the existing data to characterize optimal surgical management., Methods: A thorough literature review was conducted for full length research articles, including systematic reviews, retrospective cohort studies and case series, published between January 2000 and July 2023 regarding open, thoracoscopic or robotic thymectomy for management of JMG. Reference lists of the identified articles were manually searched for additional studies. Evidence was summarized in a narrative fashion with the incorporation of the authors' knowledge gained through clinical experience., Key Content and Findings: Although data specific to JMG are limited to small retrospective cohort studies, available evidence supports equal to greater disease control following thymectomy versus pharmacologic management. Furthermore, outcomes may be optimized when surgery is performed earlier in the disease course, particularly for patients who are post-pubertal with generalized or severe disease and those necessitating high-dose steroid administration thereby limiting its metabolic and growth inhibitory effects. Open transsternal resection is the historic gold-standard; however, as surgeons become more comfortable with thoracoscopic and robotic-assisted thymectomy, an increasing proportion of patients are expected to undergo thymectomy. At present, the data available is unable to support conclusions regarding which surgical approach is superior; however, minimally invasive approaches may be non-inferior while offering superior cosmesis and decreased morbidity., Conclusions: Higher-level investigation through the use of multi-institutional databases and randomized prospective trials is warranted in order to understand which child warrants thymectomy, at what point in their disease course and their development, and which surgical approach will optimize postoperative outcomes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-23-41/coif). The authors have no conflicts of interest to declare., (2024 Mediastinum. All rights reserved.)