Genetically engineered mouse model of pleomorphic liposarcoma: Immunophenotyping and histologic characterization.

INTRODUCTION: Pleomorphic liposarcoma is a rare and aggressive subset of soft-tissue sarcomas with a high mortality burden. Local treatment largely consists of radiation therapy and wide surgical resection, but options for systemic therapy in the setting of metastatic disease are limited and largely ineffective, prompting exploration of novel therapeutic strategies and experimental models. As with other cancers, sarcoma cell lines and patient-derived xenograft models have been developed and used to characterize these tumors and identify therapeutic targets, but these models have inherent limitations. The establishment of genetically engineered mouse models represents a more realistic framework for reproducing clinically relevant conditions for studying pleomorphic liposarcoma. METHODS: Trp53fl/fl/Rb1fl/fl/Ptenfl/fl (RPP) mice were used to reliably generate an immunocompetent model of mouse pleomorphic liposarcoma through Cre-mediated conditional silencing of the Trp53, Rb1, and Pten tumor suppressor genes. Evaluation of tumor-infiltrating lymphocytes was assessed with immunostaining for CD4, CD8, and PD-L1, and flow cytometry with analysis of CD45, CD3, CD4, CD8, CD19, F4/80, CD11b, and NKp46 sub-populations. RESULTS: Mice reliably produced noticeable soft-tissue tumors in approximately 6 weeks with rapid tumor growth between 100 and 150 days of life, after which mice reached euthanasia criteria. Histologic features were consistent with pleomorphic liposarcoma, including widespread pleomorphic lipoblasts. Immunoprofiling and assessment of tumor-infiltrating lymphocytes was consistent with other soft-tissue sarcomas. CONCLUSION: Genetically engineered RPP mice reliably produced soft-tissue tumors consistent with pleomorphic liposarcoma, which immunological findings similar to other soft-tissue sarcomas. This model may demonstrate utility in testing treatments for this rare disease, including immunomodulatory therapies.

Thermal properties of polymethyl methacrylate vary depending on brand and type.

Polymethyl methacrylate (PMMA) is commonly used in orthopedic surgery and has several applications, most often for fixation of arthroplasty components. While its overall safety and tolerance are well described, less is known regarding the thermal properties of PMMA as it sets from a liquid to solid state, as well as the potential for osseous thermal necrosis. This study addresses potential variations in the setting time and maximum temperature of PMMA formulations in common use and explores the potential clinical implications of this variability. Seven commercially available formulations of PMMA that varied by brand and/or viscosity were obtained and prepared according to manufacturer's instructions. Peak temperature and duration were measured in controlled settings for each type and compared to previously described thresholds for thermal bone necrosis. Depuy SmartSet (HV), Zimmer Palacos R (HV), and Zimmer Palacos (LV) exceeded the 56°C threshold reported to potentially induce immediate osseous thermal necrosis. Additionally, Biomet Cobalt (MV) and Stryker Simplex P (MV) had lower peak temperatures but exceeded thermal necrosis thresholds due to curing duration. The lowest peak temperature was observed for Smith & Nephew Versabond (MV), which was significantly lower than all types except Depuy SmartSet (MV). Setting time was not significantly different among groups. There are significant differences in the thermal properties of PMMA formulations in current use. Selection of specific PMMA formulations represents an additional route of procedural optimization depending on the needs of the treating surgeon.

Ewing sarcoma of the pelvis: Clinical features and overall survival.

INTRODUCTION: Primary Ewing Sarcoma of Bone is a malignancy whose treatment requires both systemic chemotherapy and local control through surgical resection and/or radiation. Ewing Sarcoma of the pelvis has been noted to confer a worse prognosis relative to other anatomic sites of Ewing Sarcoma. This study explores the presenting features, treatment modalities for local control, and overall survival of primary Ewing sarcoma of the pelvis in comparison to other commonly affected anatomic sites. METHODS: The National Cancer Institute Surveillance, Epidemiology, and End-Results (SEER) database was used to identify cases of pelvic Ewing sarcoma diagnosed between years 2004 and 2015. Demographic variables including sex, race, and age at diagnosis were described for each case, as well as therapeutic modalities including surgery and radiation. Bone-specific Collaborative Staging variables, including tumor size, tumor extension, and metastasis at diagnosis, were described for the same cohort. Univariate and multivariate assessments were performed for statistical comparison between presenting factors, treatment modalities, and between anatomic locations of presentation. RESULTS: Within the database, 296 patients with Ewing sarcoma of the pelvic bones were available for review, which represented 25.7% of the 1152 cases surveyed across all anatomic sites. In the subset of patients with Ewing Sarcoma of the pelvis, 63.5% were male; the median age of diagnosis was 17 years; extra-compartmental tumor extension was noted in 82.1%; average tumor size was 9.7 cm; and metastasis at diagnosis was noted in 46.1% of the cohort. Only 28.6% of the pelvis sarcoma patients received surgical resection as part or all of their local control treatment, while 67.6% received some form of radiation therapy. When compared to the presenting features of Ewing Sarcoma from other anatomic sites, patients with pelvic tumors had larger tumors at time of diagnosis, higher rates of metastatic disease, and were less likely to undergo surgical intervention. The 2-, 5-, and 10-year overall survival rates for the patients presenting with Ewing Sarcoma of the pelvis was 70.3%, 49.7%, and 41.9%, respectively, which were significantly lower across all time-points than any other anatomic site. DISCUSSION AND CONCLUSION: Ewing Sarcoma of the pelvis is an aggressive malignancy that presents with relatively large tumors and a high rate of metastatic dissemination. Surgical intervention is less frequent when Ewing Sarcoma presents in the pelvis than when it presents in other anatomic locations. These factors may contribute to the worse overall survival of Ewing Sarcoma when compared to the same diagnosis originating in other anatomic sites. Prospective, randomized study is required to determine the true causal effects of these factors on survival.

Extraskeletal myxoid chondrosarcoma: Clinical features and overall survival.

INTRODUCTION: Extraskeletal myxoid chondrosarcoma is a rare form of soft tissue sarcoma characterized by a unique chromosomal translocation involving the NR4A3 gene on chromosome 9. It is most frequently diagnosed in the proximal extremities of older adult males and is notable for its insidious growth with predilection for local recurrence and metastasis. Currently, extraskeletal myxoid chondrosarcoma is managed with wide resection, with recent investigations supporting the utility of adjuvant radiation and novel chemotherapeutic strategies. METHODOLOGY: A retrospective study was performed with the Surveillance, Epidemiology, and End-Results (SEER) database, which was searched for cases of extraskeletal myxoid chondrosarcoma diagnosed between years 2004 and 2015. Demographic variables were assessed, as well as Collaborative Staging variables including tumor size, metastatic disease, grade, and lymph node involvement. Cases were stratified according to the anatomic site of the primary tumor and were described by therapeutic intervention. A multivariate Cox proportional hazards model evaluated predictive factors for poor survival, and Kaplan-Meier analyses assessed effects of various staging, demographic, and therapeutic variables on overall survival. RESULTS: There were 270 cases of extraskeletal myxoid chondrosarcoma reviewed in this study, which were diagnosed most frequently in the lower limb or hip of older adult males. The 5-year overall survival was 76.5% and was worse on univariate assessment for patients with age > 60, high histologic grade, pelvic location, tumor size > 8.0 cm, metastatic or nodal spread, and in patients without surgical intervention. The Cox regression predicted significantly worse survival for older age, larger tumor size, non-surgical status, and high tumor grade. Metastasis did not significantly predict worse survival on multivariate assessment, and neither chemotherapy nor radiotherapy provided a discernable improvement in survival in this cohort. DISCUSSION AND CONCLUSION: As a rare soft tissue sarcoma, many of the presenting features and survival outcomes of extraskeletal myxoid chondrosarcoma remain poorly defined due to the limited prevalence of this disease. The findings of this study suggest the overall survival may be worse than previously reported, and poor prognostic factors are those associated with worse survival in other soft tissue sarcomas, including high histologic grade, older age, larger tumor size, and lack of wide resection. Radiation and chemotherapy did not demonstrably improve survival for patients with localized or metastatic disease.

Presenting features and overall survival of chondrosarcoma of the pelvis.

INTRODUCTION: Chondrosarcoma is the second most common sarcoma of bone. This sarcoma is generally unresponsive to chemotherapy and radiation and is primarily managed through surgical excision. Pelvic chondrosarcoma presents a distinct therapeutic challenge due the complexity of resection, frequent recurrence and metastasis, and high post-operative morbidity. METHODS: The SEER database was queried for pelvic chondrosarcoma diagnosed between 2004 and 2015. Cases were described by age, sex, tumor size, extension, grade, metastasis, and therapeutic intervention. These same variables were assessed for the upper extremities, lower extremities, skull and facial bones, thoracic bones, and vertebral column. RESULTS: In total, 472 cases of pelvic chondrosarcoma were identified, representing 18.4% out of 2571 cases of chondrosarcoma distributed throughout the skeletal system. Among pelvic cases, 288 were male and 184 were female, with a median age of diagnosis of 54. Median tumor size was 96 mm, 64.9% of tumors were considered extracompartmental, and 11.3% of tumors were metastatic at time of diagnosis. The 2, 5, and 10-year survival rates for all cases of primary chondrosarcoma of the pelvis are 76.7%, 61.8%, and 52.2%, respectively. Survival was worse for patients with metastasis, male sex, age >60, tumor size >8 cm, dedifferentiated histology, and no surgical resection. On multivariate assessment high grade and metastasis most significantly predicted worse overall survival. CONCLUSION: Pelvic chondrosarcoma commonly presents with high-risk features including larger tumor size, extracompartmental extension, and metastatic disease at diagnosis, predicting worse overall survival compared to non-pelvic tumors, and were the least amenable to surgical resection.

Yoga as an Adjunct Therapy for Musculoskeletal Pain and Burnout in Orthopedic Surgery: A Trainee's Perspective.

Orthopedic surgeons face significant physical and psychosocial stressors during their training as surgical residents and throughout their career. Aside from occupational hazards intrinsic to the profession, two notable and treatable concerns are musculoskeletal pain and emotional burnout, which have a reported prevalence as high as 97% and 56%, respectively, among orthopedic residents. Management of musculoskeletal pain and burnout is essential for promoting surgeon well being, education, and longevity as well as avoiding medical errors and compromises to patient care. This perspective manuscript describes the occupational challenges faced by orthopedic surgeons and promotes a habitual practice of yoga as an adjunct therapy for managing musculoskeletal pain and emotional burnout, and furthermore, introduces the need to reconsider gendered perceptions surrounding orthopedics and the practice of yoga in a profession largely comprised of men.

Osteosarcoma of the Pelvis: Clinical Presentation and Overall Survival.

INTRODUCTION: Osteosarcoma is the most common sarcoma of bone. Pelvic osteosarcoma presents a significant therapeutic challenge due to potential late symptom onset, metastatic dissemination at diagnosis, and inherent difficulties of wide surgical resection secondary to the complex and critical anatomy of the pelvis. The rates of survival are well reported for osteosarcoma of the appendicular skeleton, but specific details regarding presentation and survival are less known for osteosarcoma of the pelvis. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program was queried for primary osteosarcoma of the bony pelvis from 2004 to 2015. Cases with Collaborative Staging variables (available after 2004) were analyzed by grade, histologic subtype, surgical intervention, tumor size, tumor extension, and presence of metastasis at diagnosis. The 2-, 5-, and 10-year survival rates were assessed with respect to these variables. The SEER database was then queried for age, tumor size, surgical intervention, metastasis at time of presentation, and survivorship data for patients with primary osteosarcoma of the upper extremity, lower extremity, vertebrae, thorax, and face/skull, and rates for all anatomic locations were then compared to patients with primary pelvic osteosarcoma. RESULTS: A total of 292 cases of pelvic osteosarcoma were identified from 2004 to 2015 within the database, representing 9.8% of cases among all surveyed primary sites. The most common histologic subtype was osteoblastic osteosarcoma (69.9%), followed by chondroblastic osteosarcoma (22.3%). The majority of cases were high-grade tumors (94.3%), of size >8 cm (72.0%), and with extension beyond the originating bone (74.0%). For the entire pelvic osteosarcoma group, the 2-, 5-, 10-year survival rates were 45.6%, 26.5%, and 21.4%, respectively, which were the poorest among surveyed anatomic sites. The 5-year overall survival was an abysmal 5.3% for patients with metastatic disease at diagnosis, and 37.0% for non-metastatic pelvic osteosarcoma treated with surgery and chemotherapy. When compared to other locations, pelvic osteosarcoma had higher rates of metastatic disease at presentation (33.5%), larger median tumor size (11.0 cm), and older median age at diagnosis (47.5 years). While over 85% of patients with tumors at the extremities received surgery, only 47.4% of pelvic osteosarcomas in this cohort received surgical resection-likely influenced by larger tumor size, sacral involvement, frequency of metastasis, older age, or delayed referral to a sarcoma center. CONCLUSION: This study clarifies presenting features and clinical outcomes of pelvic osteosarcomas, which often present with large, high-grade tumors with extracompartmental extension, high likelihood of metastatic disease at diagnosis, and a potential limited ability to be addressed surgically. The survival rates of primary osteosarcoma of the pelvis are poor and are lower than osteosarcomas from other anatomic locations. While acknowledging the influence of metastasis, tumor characteristics, and advanced age on the decision to undergo surgical excision of a pelvic osteosarcoma, the rates of surgical resection are low and highlight the importance of understanding appropriate conditions for oncologic resection of pelvic sarcomas.