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IntroductionThe overall survival rate of patients with osteosarcoma (OS) and pulmonary metastases has remained stagnant at 15–30% for several decades. Disulfiram (DSF) is an FDA-approved aldehyde dehydrogenase inhibitor that reduces the metastatic phenotype of OS cells in vitro. Here we evaluate its in vivo efficacy, as compared to doxorubicin chemotherapy, in a previously-validated orthotopic model of metastatic OS.ResultsAll treatment groups displayed a significantly reduced quantitative OS metastatic burden compared with controls. The metastatic burden of Lo DSF-treated animals was equivalent to the DXR group. Ninety-five percent of control animals displayed evidence of metastatic disease, which was significantly greater than all treatment groups.DiscussionDisulfiram treatment resulted in a reduced burden of OS metastatic disease compared with controls. This was statistically-equivalent to doxorubicin. No additive effect was observed between these two therapies.Materials and MethodsOne-hundred twenty immunocompetent Balb/c mice received proximal tibia paraphyseal injections of 5 × 105 K7M2 murine OS cells. Therapy began three weeks after injection: saline (control), low-dose disulfiram (Lo DSF), high-dose disulfiram (Hi DSF), doxorubicin (DXR), Lo DSF + DXR, and Hi DSF + DXR. Transfemoral amputations were performed at 4 weeks. Quantitative metastatic tumor burden was measured using near-infrared indocyanine green (ICG) angiography.

Background Surgical resection with negative margins is the foundation of extremity sarcoma management. Failure to achieve negative surgical margins can result in local recurrence (LR), a potentially devastating complication. Indocyanine green (ICG) is a US FDA-approved fluorophore previously used to guide carcinoma resections. We investigated the potential of ICG as an intraoperative guide during experimental sarcoma resection. Methods Fifty 6-week-old immunocompetent Balb/c female mice received left proximal tibia paraphyseal injections of 5 × 10 5 K7M2 murine osteosarcoma cells. Animals were separated into two groups ( n = 25 each): (1) ICG-assisted surgical resection; and (2) no ICG-assisted resection. Resections were performed 4 weeks after primary tumor engraftment. All animals received 7.5 ug ICG via retro-orbital injection 12 h prior to surgery. ICG fluorescence measurements and clinical evaluations were performed 4 weeks after resection to detect LR. Results Eleven of 25 animals from each group developed gross tumors. Four weeks after resection, group 1 had 0/11 tumor recurrences, while group 2 had recurrences in 9/11 (81.8%) experimental mice ( p < 0.0002) (Fig. 2 ). There was a 100% NPV in group 1, and no tumor recurrence with fluorescence-free margins after the primary surgery. Group 2 had a 100% positive predictive value for the development of an LR if any fluorescent signal was present at the surgical margin after resection. Conclusion Intraoperative ICG guidance led to reliably negative surgical margins and a diminished LR rate. Given the benign safety profile of ICG and its prior clinical success, these results could be immediately translatable to the clinical realm.

Background: The importance of research in resident education has been emphasized in the orthopaedic surgery community, and a number of residency programs have incorporated a year or more of protected research time into their training. However, limited information exists as to what programs are looking for in applicants to research-track residency programs or the perceived benefits of completing such a program. Methods: We identified orthopaedic surgery programs that have tracks involving at least 1 year of protected research time and sent surveys to their program directors and to the 2012 through 2016 research-track graduates. Results: Twenty-three programs with research tracks were identified, and 19 program directors (83%) responded to the survey. The survey revealed that only 2 (11%) of these program directors were willing to accept lower scores and grades among applicants to their research track compared with their primary clinical (categorical) track. While most of the program directors (14 [74%]) preferred that applicants have an interest in academics, only a few (3 [16%]) considered it a failure if their research-track residents did not pursue academic careers. We obtained the e-mail addresses of 82 research-track graduates, and 66 (80%) responded to the survey. The survey revealed that those who went into academic careers were more likely than those who went into private practice to view completing a research track as beneficial for fellowship (73% versus 35%, respectively) and job (73% versus 22%, respectively) applications, believed that the income lost from the additional year of residency would be compensated for by opportunities gained from the research year (50% versus 17%, respectively), and said that they would pursue a research-track residency if they had to do it over again (81% versus 39%, respectively; all p values <0.05). Conclusions: The majority of program directors preferred that applicants to their research-track program have an interest in academics, although most did not consider it a failure if their research-track residents entered nonacademic careers. Graduates of research-track residency programs who entered academics more frequently viewed the completion of a research track as being beneficial compared with those who went into private practice.

OBJECTIVE The goal of this study was to use 4 prognostic indices to compare survival times of patients who underwent Gamma Knife stereotactic radiosurgery (SRS) to treat melanoma brain metastases. METHODS The authors analyzed 422 consecutive patients (1440 brain metastases) who underwent Gamma Knife SRS. The median total brain tumor volume was 4.7 cm (range 0.3-69.3 cm), and the median number of metastases was 2 (range 1-32). One hundred thirty-two patients underwent whole-brain radiation therapy. Survival times were compared using recursive partitioning analysis (RPA), the Score Index for Radiosurgery (SIR), the Basic Score for Brain Metastases (BSBM), and the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA). RESULTS The overall survival times after SRS were compared. With the RPA index, survival times were 2.6 months (Class III, n = 27), 5.5 months (Class II, n = 348), and 13.0 months (Class I, n = 47). With the DS-GPA index, survival times were 2.8 months (Scores 0-1, n = 67), 4.2 months (Scores 1.5-2.0, n = 143), 6.6 months (Scores 2.5-3.0, n = 111), and 9.4 months (Scores 3.5-4.0, n = 101). With the SIR, survival times were 3.2 months (Scores 0-3, n = 56), 5.8 months (Scores 4-7, n = 319), and 12.7 months (Scores 8-10, n = 47). With the BSBM index, survival times were 2.6 months (BSBM0, n = 47), 5.4 months (BSBM1, n = 282), 11.0 months (BSBM2, n = 86), and 8.8 months (BSBM3, n = 7). The DS-GPA index was the most balanced by case numbers in each class and provided the overall best prognostic index for overall survival. CONCLUSIONS The DS-GPA index proved most balanced and predictive of survival for patients with melanoma who underwent SRS as part of management for brain metastases. Patients whose DS-GPA score was ≥ 2.5 had predictably improved survival times after SRS.