Autophagy in Osteosarcoma.

Osteosarcoma (OS) remains a difficult disease to treat. The standard chemotherapy regimen has not improved survival for the past three decades. Resistance to chemotherapy remains a challenge and constitutes a major concern to clinical investigators. Autophagy has been recognized as a survival mechanism implicated in resistance to chemotherapy. We previously demonstrated chemotherapy to induce autophagy in OS. However, whether induction of autophagy will lead to survival or death has been the focus of many laboratories. Autophagy is a very context-dependent process, and no specific biomarker has been identified to define whether the process will lead to survival or death. In the present chapter, we present some of the mechanisms involved in the process of autophagy and summarize some of the most recent work related to autophagy in OS and the challenges encountered with the use of old and new autophagy inhibitors.

Posttreatment Maturation of Medulloblastoma into Gangliocytoma: Report of 2 Cases.

INTRODUCTION: We report 2 cases of medulloblastoma maturing into gangliocytoma after receiving multimodal therapy. Here we present 2 cases of diagnosed medulloblastoma which on re-resection were noted to be gangliocytoma without heterogeneity, which is an extremely rare occurrence. CASE PRESENTATION: The first patient, an 11-year-old boy diagnosed with high-risk (non-WNT, non-SHH) medulloblastoma, was treated with near-total surgical resection followed by craniospinal radiation therapy with weekly vincristine. He then received maintenance chemotherapy with vincristine, cyclophosphamide, and cisplatin. On surveillance MR imaging studies residual tumor in the lateral aspect of the tumor bed was noted to be slowly growing, eliciting gross-total resection of the residual tumor. Histopathology showed benign gangliocytoma without residual medulloblastoma. The second patient, a 3-year-old girl, was diagnosed with medulloblastoma, desmoplastic nodular variant. She was initially treated with gross total resection and chemotherapy with etoposide, carboplatin, and high-dose methotrexate. At 4 months off therapy, she was noted to have local recurrence along the resection cavity. Second-line therapy was started with irinotecan and temozolomide, but MRI assessment during treatment showed further disease progression. She then received craniospinal radiation. Eleven months off therapy, further radiographic progression was noted, and the patient underwent second-look surgery, with pathology showing gangliocytoma and treatment-related gliosis. DISCUSSION/CONCLUSION: The maturation of medulloblastoma into a ganglion cell-rich lesion is very rare, with few well-characterized previous reports. Given the rare nature of this entity, it would be of great value to understand the process of posttreatment maturation and the genetic and treatment factors which contribute to this phenomenon.

Group Evaluations of Individual Faculty Hospitalists.

INTRODUCTION: Faculty evaluations are important tools for improving faculty-to-resident instruction, but residents in our pediatric and internal medicine/pediatric residency programs would seldom evaluate individual pediatric faculty hospitalists. Our objectives were to: (1) increase the percentage of completed evaluations of individual pediatric hospitalists to greater than 85%, (2) improve the quality of pediatric hospitalist feedback as measured by resident and faculty satisfaction surveys, and (3) to reduce the resident concern of lack of anonymity of evaluations. METHODS: Members of the resident inpatient team (pediatric and internal medicine/pediatric residents) completed group-based evaluations of individual pediatric hospitalists. A survey to evaluate this change in process was distributed to the pediatric hospitalists (n = 6) and another survey was distributed to residents, both based on a 5-point Likert-type scale. Surveys were completed before and four months after implementation of the changes. Pre- and post-survey data of resident and hospitalist responses were compared using the Mann-Whitney test and probability proportion test. RESULTS: The percent of completed evaluations increased from 0% to 86% in one month and to 100% in two months. Thereafter, the percent of completed evaluations remained at 100% through the end of the data collection period at seven months. Hospitalists reported (n = 6, 100% participation) their satisfaction regarding the feedback they received from residents significantly increased for all survey questions. Resident satisfaction (n = 24, 89% participation in post-intervention surveys) increased significantly with regards to the evaluation process. CONCLUSIONS: For hospitalists, group-based resident evaluations of individual hospitalists led to an increased percentage of completed evaluations, improved the quality and quantity of feedback to hospitalists, and increased satisfaction with evaluations. For residents, these changes led to increased satisfaction with the evaluation process.