3400 Introduction: Carbamazepine (CBZ), an established sodium channel blocker, used in treatment of epilepsy and trigeminal neuralgia, induces autophagy. CBZ has recently been demonstrated to be an ionizing radiation mitigator and protector (Kim,H.et. al IJRB-in press). CBZ protected C57BL/6NHsd female mice from irradiation if given 24 hr before total body irradiation (TBI) and mitigated if given 12 hours after irradiation. Materials and Methods: To elucidate the mechanism of CBZ action, autophagy incompetent (ATG5−/−) and competent (ATG5+/+) mouse embryo fibroblasts (MEF), p53−/− and p53+/+ bone marrow stromal cells and 32D cl 3 murine IL-3 dependent hematopoietic progenitor cells were tested for CBZ mediated radiation protection and mitigation in clonagenic irradiation survival curves. We also measured CBZ effect on irradiation-induced apoptosis, and depletion of antioxidant stores in vitro and after (TBI) in vivo in control mice and in hind limb irradiated mice with orthotopic tumors. Results: CBZ was a significant radiation protector and mitigator for both ATG5−/− and ATG5 +/+ cell lines by an increased ñ (a measurement of the shoulder on the clonogenic survival curve). CBZ treated ATG5 +/+ cells has an increased ñ of 11.1 +/− 0.2 or 8.8 +/− 0.2 for CBZ added before or after irradiation respectively compared to 5.4 +/− 0.9 for irradiation control cells (p = 0.0287 or 0.0119,respectively). ATG −/− cells were also protected and mitigated by CBZ (ñ of 16.1 +/− 2.6 as a radioprotector or 9.8 +/− 1.5 as a mitigator compared to 4.6 +/− 0.7 for irradiated control cells (p = 0.0002 or 0.0037, respectively). Thus, CBZ functions independent of autophagy. Incubation of p53 +/+ and p53−/− cell lines in 10 μM CBZ for one hour before irradiation protected (ñ of 5.6 +/− 0.9 compared to 1.9 +/− 0.5 for control irradiated p53 +/+ cells (p = 0.0126) and 3.7 +/− 1.9 compared to 1.8 +/− 0.4 for irradiated control p53 −/− cells (p = 0.0018). Thus, CBZ functions in a p53 independent manner. Other pro-autophagy drugs, Valproic Acid and Lithium Carbonate, were ineffective radiation protectors or mitigators. CBZ treatment of 32D cl 3 cells for one hour before or immediately following irradiation had no effect on mitochondrial membrane depolarization, apoptosis or viability but was protective and mitigative in clonagenic survival curve assays. Irradiation initially decreased antioxidant stores in both ATG5+/+ and ATG5−/− cells 10 to 30 min following irradiation. However, cells treated with CBZ had a faster recovery of antioxidant stores to pre-irradiation levels by 90 min compared to 120 min for control irradiated cells. To determine if CBZ protected both normal tissues and tumors in vivo mice with 3LL Lewis Lung carcinoma hind limb xenografts were treated with 10 mg/kg CBZ before or after 20 Gy limb irradiation. There was no significant difference in tumor growth inhibition by 20 Gy in mice treated with CBZ before or after irradiation (p = 0.2431 or 0.5439, respectively). Conclusion: Thus, CBZ is an effective radiation protector and mitigator of normal but not tumor tissues by a novel mechanism independent of autophagy, p53 and apoptosis. Acknowledgments: This project was supported by U191A168021–06. Disclosures: No relevant conflicts of interest to declare.
Pulmonary sling is the anatomic variant defined by the aberrant origin of the left pulmonary artery from the right pulmonary artery. This patient presented with a mimic of pulmonary sling as a result of an extremely rare condition, arterial tortuosity syndrome (ATS). The patient was first diagnosed with pulmonary sling on prenatal echocardiogram performed by cardiology. Computed tomography angiography of the chest obtained at birth to evaluate respiratory depression demonstrated ATS. The early detection of ATS has been demonstrated to improve patient outcome. This case provides an overview of the typical imaging features of ATS to aid radiologists in making this uncommon diagnosis.
Liposarcoma of the larynx is a rare entity, typically well differentiated with a good prognosis. We present a patient who presented to ENT clinic with a 3-month history of hoarseness. Contrast-enhanced computed tomography of the neck demonstrated a 2.5-cm mass of the true vocal cord, which biopsy demonstrated to be dedifferentiated liposarcoma of the larynx. The patient went on to total laryngectomy with planned adjuvant radiation therapy. The presentation and imaging findings of laryngeal liposarcoma are nonspecific, but this neoplasm should be considered in the differential of masses in the head and neck.
Pediatric radiology departments across the globe face unique challenges in the midst of the current COVID-19 pandemic that have not been addressed in professional guidelines. Providing a safe environment for personnel while continuing to deliver optimal care to patients is feasible when abiding by fundamental recommendations. In this article, we review current infection control practices across the multiple pediatric institutions represented on the Society for Pediatric Radiology (SPR) Quality and Safety committee. We discuss the routes of infectious transmission and appropriate transmission-based precautions, in addition to exploring strategies to optimize personal protective equipment (PPE) supplies. This work serves as a summary of current evidence-based recommendations for infection control, and current best practices specific to pediatric radiologists.
Objectives: 18F-fluciclovine (fluciclovine) is an amino acid analog approved by the Food and Drug Administration for use as a radiotracer in positron emission tomography (PET) in men with biochemical recurrence of suspected prostate cancer. The purpose of this study was to investigate the initial institutional experience with 18F-fluciclovine in the evaluation of prostate cancer with biochemical recurrence.Methods: This study was a retrospective review of 135 patients who underwent 18F-fluciclovine PET-computed tomography (PET-CT) at a single institution from August 2018 through January 2020. Prognostic information, including prostate-specific level antigen (PSA) at the time of diagnosis, initial risk, initial Gleason score, and initial stage, was reviewed as well as the PSA level at the time of the scan. The images were reviewed by two radiologists with fellowship training in nuclear medicine and additional training to interpret the fluciclovine studies. A minority of studies were reviewed by a third fellowship-trained radiologist under the guidance of the two nuclear medicine-trained radiologists. In cases with abnormal radiopharmaceutical uptake in lymph nodes, the short-axis dimension of the lymph node or largest lymph node with abnormal uptake was noted. If CT or bone scan was performed within 4 months of the 18F-fluciclovine PET-CT, findings on the alternate imaging were compared with the results of the 18F-fluciclovine PET-CT.Results: Our institutional positivity rate was 75.6%, with 64 (67.4%) patients with metastatic disease and 71 (52.6%) patients with local recurrence detected by fluciclovine. As expected, the rate of positive examinations increased with increasing PSA values measured at the time of imaging ( P < 0.001). Of the 54 patients with nodal disease, 35 had nonpathologically enlarged lymph nodes measuring <1 cm in maximum short-axis dimension. In more than half of the patients in this study, with conventional imaging, fluciclovine either discovered otherwise undetectable metastatic disease or suggested the presence of local recurrence.Conclusions: Our single-institution experience with 18F-fluciclovine PET-CT has the largest number of patients to date in the literature and demonstrates the ability of fluciclovine to help guide clinical management in the detection of early recurrent disease.
Dysembryoplastic neuroepithelial tumors (DNETs) are typically benign World Health Organization (WHO) grade I tumors of the cortical or deep gray matter with a favorable prognosis. We encountered a patient with DNET who has been evaluated and treated for West Nile encephalitis 7 months before presentation. Over the course of 2 years, the patient developed diffuse leptomeningeal carcinomatosis. As the disease burden increased, the patient eventually became quadriparetic. The patient elected for hospice care and expired shortly thereafter. Autopsy revealed DNET (WHO grade I) with extensive involvement of the cervical, thoracic, and lumbar spinal cord, bilateral cerebellar hemispheres, brainstem, the cortex of the right frontal and temporal lobes, and meningeal carcinomatosis of the brain and spinal cord. Mortality from DNET is rare, and as per our extensive literature search, there has been only 1 case reported of death attributed to seizures from this diagnosis. To the best of our knowledge, this is the only case of disseminated DNET with meningeal infiltration or carcinomatosis resulting in mortality.
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