Left Ventricle Size Correlates with Peak Exercise Capacity in Pediatric Cancer Survivors Exposed to Anthracycline Chemotherapy.

Cancer survivors exposed to anthracycline chemotherapy are at risk for developing cardiomyopathy, which may have delayed clinical manifestation. In a retrospective cross-sectional study, we evaluated the utility of cardiopulmonary exercise testing (CPET) for detecting early cardiac disease in 35 pediatric cancer survivors by examining the associations between peak exercise capacity (measured via percent predicted peak VO2) and resting left ventricular (LV) function on echocardiography and cardiac magnetic resonance imaging (cMRI). We additionally assessed the relationships between LV size on resting echocardiography or cMRI and percent predicted peak VO2 since LV growth arrest can occur in anthracycline-exposed patients prior to changes in LV systolic function. We found reduced exercise capacity in this cohort, with low percent predicted peak VO2 (62%, IQR: 53-75%). While most patients in our pediatric cohort had normal LV systolic function, we observed associations between percent predicted peak VO2 and echocardiographic and cMRI measures of LV size. These findings indicate that CPET may be more sensitive in manifesting early anthracycline-induced cardiomyopathy than echocardiography in pediatric cancer survivors. Our study also highlights the importance of assessing LV size in addition to function in pediatric cancer survivors exposed to anthracyclines.

Kaposiform hemangioendothelioma of the bone in children and adolescents.

Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor that mainly occurs during infancy or early childhood. Approximately 70% of cases are complicated by Kasabach-Merritt phenomenon. Although osseous extension of the primary lesion is relatively common, primary bone involvement by KHE is rare. Given the paucity of literature on primary KHE of the bone, we report a case series of primary KHE of the bone treated at our institution and describe the clinical presentation, radiologic and pathologic findings, management and outcomes.

Young Adult With Osteosarcoma of the Mandible and the Challenge in Management: Review of the Pediatric and Adult Literatures.

Neoadjuvant chemotherapy for osteosarcoma of the jaw (OSJ) remains controversial despite being a standardized treatment in osteosarcoma of the long bones. We present a case of a 22-year-old male with OSJ and performed a retrospective systemic review of previously published literatures of OSJ. We identified 27 articles: 7% recommended neoadjuvant chemotherapy, 22% recommended adjuvant chemotherapy, 19% recommended both neoadjuvant and adjuvant chemotherapy, 33% recommended against chemotherapy and 19% stated the role of chemotherapy is unknown. The lack of consensus regarding the use of chemotherapy in OSJ, despite its benefits, demonstrates the need to establish a standardized algorithm for OSJ.

Docetaxel, bevacizumab, and gemcitabine for very high risk sarcomas in adolescents and young adults: A single-center experience.

BACKGROUND: Adolescent and young adult (AYA) patients with very high risk sarcomas have poor outcomes and are in need of novel therapies. PROCEDURE: From January 2005 to February 2016, we retrospectively identified all AYA patients with relapsed or metastatic high-grade sarcomas, who were treated with at least one cycle of docetaxel (T), bevacizumab (A), and gemcitabine (G) (TAG ; T = 100 mg/m2 Day 8, A = 15 mg/kg Day 1, G = 1,000 mg/m2 Days 1 and 8). RESULTS: Fourteen patients, median age of 20 (15-30), received a total of 80 cycles of TAG, and were followed for a median of 83 months. Diagnosis included osteosarcoma (OST; 8), Ewing sarcoma (3), and soft tissue sarcoma (3). Five of 14 patients achieved clinical remission (CR), 3 had partial responses (PR), 3 had stable disease (SD), and 3 had progressive disease (PD). The median progression-free survival and overall survival were 7 and 19 months, respectively. The objective response rate (CR + PR) and tumor control rate (CR + PR + SD) were 57% and 79%, respectively, with two patients alive after 5 years; toxicities included thrombocytopenia, neutropenia, and capillary leak syndrome. CONCLUSIONS: Our study builds on previous studies utilizing TAG in adult leiomyosarcoma (LMS) by focusing on AYA, non-LMS sarcomas, especially OST. Our experience suggests that TAG is well tolerated and has activity in very high risk sarcomas in AYA.

Osteosarcoma Metastases With Direct Cardiac Invasion: A Case Report and Review of the Pediatric Literature.

Metastatic osteosarcoma with direct cardiac involvement is an exceptionally rare finding, with only 63 total reported cases in the English literature over the past 123 years. Although the precise incidence is unknown, we estimate that direct cardiac involvement currently occurs in <2% of metastatic osteosarcoma cases. We also find that before the adoption of adjuvant chemotherapy as a standard of care therapy for osteosarcoma, metastatic osteosarcoma to the heart was much more common than it is today, as cardiac involvement occurred in ∼20% of cases of metastatic osteosarcoma before the 1980s. This suggests that adjuvant chemotherapy has not only improved the overall prognosis of osteosarcoma, but also altered the metastatic pattern of disease. In this paper we present the case of an 11-year-old boy with metastatic osteosarcoma to the cardiac interventricular septum, as well as review 20 other previously reported pediatric cases of metastatic osteosarcoma to the heart. We also analyzed the cardiac surgical outcomes for 11 pediatric patients with metastatic osteosarcoma to the heart. The median disease-free survival time was 12 months, demonstrating that metastatic osteosarcoma to the heart is currently a rare occurrence with a poor prognosis.

Seed Becoming Soil: A New Paradigm of the Ewing Sarcoma Tumor Microenvironment.

Cells in the tumor microenvironment, including cancer-associated fibroblasts (CAF), contribute to tumor growth and immune evasion. A recent study of Ewing sarcoma identified "CAF-like" tumor cells that mimic the protumorigenic features of CAFs. These findings highlight the role of cell plasticity in tumor growth. See related article by Wrenn et al., p. 5140.

Survival outcomes and surgical morbidity based on surgical approach to pulmonary metastasectomy in pediatric, adolescent and young adult patients with osteosarcoma.

BACKGROUND: Thoracotomy is considered the standard surgical approach for the management of pulmonary metastases in osteosarcoma (OST). Several studies have identified the advantages of a thoracoscopic approach, however, the clinical significance of thoracotomy compared to thoracoscopy is yet to be evaluated in a randomized trial. AIMS: The primary aim was to determine the survival outcomes in OST patients based on surgical approach for pulmonary metastasectomy (PM) and secondary aim was to assess the post-operative morbidities of OST PM through various surgical approaches. MATERIALS AND METHODS: We conducted a single institution retrospective study to compare survival outcomes and surgical morbidity according to the surgical approach of the management of pulmonary metastases in patients with OST. RESULTS: Sixty-one patients with OST underwent PM. Twenty-one patients were metastatic at diagnosis and underwent PM during primary treatment; nine had thoracotomy, six thoracoscopy, and six combined thoracoscopy with thoracotomy (CTT). Forty-three patients with first pulmonary relapse or progression underwent PM; 18 had thoracotomy, 16 thoracoscopy and nine CTT. There was no difference in survival between surgical approaches. There were significantly more postoperative morbidities associated with thoracotomy for initial PM (pain and postoperative chest tube placement), and for PM at first relapse (pneumothoraces, pain, Foley catheter use and prolonged hospitalizations). CONCLUSION: Our study demonstrates that patients with OST pulmonary metastases have comparable poor outcomes despite varying surgical approaches for PM. There were significantly more postoperative morbidities associated with thoracotomy for PM. Surgical bias and other competing risks could not be assessed given the limitations of a retrospective study and may be addressed in a prospective trial evaluating surgical approach for PM in OST.

Shining a light on the pathogenicity of health care providers' mobile phones: Use of a novel ultraviolet-C wave disinfection device.

BACKGROUND: Mobile phones are known to carry pathogenic bacteria and viruses on their surfaces, posing a risk to healthcare providers (HCPs) and hospital infection prevention efforts. We utilize an Ultraviolet-C (UV-C) device to provide an effective method for mobile phone disinfection and survey HCPs about infection risk. METHODS: Environmental swabs were used to culture HCPs' personal mobile phone surfaces. Four cultures were obtained per phone: before and after the UV-C device's 30-second disinfecting cycle, at the beginning and end of a 12-hour shift. Surveys were administered to participants pre- and poststudy. RESULTS: Total bacterial colony forming units were reduced by 90.5% (P = .006) after one UV-C disinfection cycle, and by 99.9% (P = .004) after 2 cycles. Total pathogenic bacterial colony forming units were decreased by 98.2% (P = .038) after one and >99.99% (P = .037) after 2 disinfection cycles. All survey respondents were willing to use the UV-C device daily to weekly, finding it convenient and beneficial. DISCUSSION: This novel UV-C disinfecting device is effective in reducing pathogenic bacteria on mobile phones. HCPs would frequently use a phone disinfecting device to reduce infection risk. CONCLUSIONS: In light of the ongoing coronavirus (COVID-19) pandemic, a standardized approach to phone disinfection may be valuable in preventing healthcare-associated infections.

Impact of MMP-2 and MMP-9 enzyme activity on wound healing, tumor growth and RACPP cleavage.

Matrix metalloproteinases-2 and -9 (MMP-2/-9) are key tissue remodeling enzymes that have multiple overlapping activities critical for wound healing and tumor progression in vivo. To overcome issues of redundancy in studying their functions in vivo, we created MMP-2/-9 double knockout (DKO) mice in the C57BL/6 background to examine wound healing. We then bred the DKO mice into the polyomavirus middle T (PyVmT) model of breast cancer to analyze the role of these enzymes in tumorigenesis. Breeding analyses indicated that significantly fewer DKO mice were born than predicted by Mendelian genetics and weaned DKO mice were growth compromised compared with wild type (WT) cohorts. Epithelial wound healing was dramatically delayed in adult DKO mice and when the DKO was combined with the PyVmT oncogene, we found that the biologically related process of mammary tumorigenesis was inhibited in a site-specific manner. To further examine the role of MMP-2/-9 in tumor progression, tumor cells derived from WT or DKO PyVmT transgenic tumors were grown in WT or DKO mice. Ratiometric activatable cell penetrating peptides (RACPPs) previously used to image cancer based on MMP-2/-9 activity were used to understand differences in MMP activity in WT or knockout syngeneic tumors in WT and KO animals. Analysis of an MMP-2 selective RACPP in WT or DKO mice bearing WT and DKO PyVmT tumor cells indicated that the genotype of the tumor cells was more important than the host stromal genotype in promoting MMP-2/-9 activity in the tumors in this model system. Additional complexities were revealed as the recruitment of host macrophages by the tumor cells was found to be the source of the tumor MMP-2/-9 activity and it is evident that MMP-2/-9 from both host and tumor is required for maximum signal using RACPP imaging for detection. We conclude that in the PyVmT model, the majority of MMP-2/-9 activity in mammary tumors is associated with host macrophages recruited into the tumor rather than that produced by the tumor cells themselves. Thus therapies that target tumor-associated macrophage functions have the potential to slow tumor progression.