RESUMEN
BACKGROUND: Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Lungs are the most frequent and often the only site of metastatic disease. The presence of pulmonary metastases is a significant unfavourable prognostic factor. Thoracotomy is strongly recommended in these patients, while computed tomography (CT) remains the gold imaging standard. The purpose of our study was to create tools for the CT-based qualification for thoracotomy in osteosarcoma patients in order to reduce the rate of useless thoracotomies. METHODS: Sixty-four osteosarcoma paediatric patients suspected of lung metastases on CT and their first-time thoracotomies (n = 100) were included in this retrospective analysis. All CT scans were analysed using a compartmental evaluation method based on the number and size of nodules. Calcification and location of lung lesions were also analysed. Inter-observer reliability between two experienced radiologists was assessed. The CT findings were then correlated with the histopathological results of thoracotomies. Various multivariate predictive models (logistic regression, classification tree and random forest) were built and predictors of lung metastases were identified. RESULTS: All applied models proved that calcified nodules on the preoperative CT scan best predict the presence of pulmonary metastases. The rating of the operated lung on the preoperative CT scan, dependent on the number and size of nodules, and the total number of nodules on this scan were also found to be important predictors. All three models achieved a relatively high sensitivity (72-92%), positive predictive value (81-90%) and accuracy (74-79%). The positive predictive value of each model was higher than of the qualification for thoracotomy performed at the time of treatment. Inter-observer reliability was at least substantial for qualitative variables and excellent for quantitative variables. CONCLUSIONS: The multivariate models built and tested in our study may be useful in the qualification of osteosarcoma patients for metastasectomy through thoracotomy and may contribute to reducing the rate of unnecessary invasive procedures in the future.
Asunto(s)
Neoplasias Óseas , Neoplasias Pulmonares , Osteosarcoma , Toracotomía , Tomografía Computarizada por Rayos X , Humanos , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/cirugía , Osteosarcoma/secundario , Osteosarcoma/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Adolescente , Niño , Estudios Retrospectivos , Masculino , Femenino , Neoplasias Óseas/secundario , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/cirugíaRESUMEN
Fusarium graminearum is the main causal agent of Fusarium head blight (FHB) disease in wheat in Europe. To reveal population structure and to pinpoint genetic targets of selection we studied genomes of 96 strains of F. graminearum using population genomics. Bayesian and phylogenomic analyses indicated that the F. graminearum emergence in Europe could be linked to two independently evolving populations termed here as East European (EE) and West European (WE) population. The EE strains are primarily prevalent in Eastern Europe, but to a lesser extent also in western and southern areas. In contrast, the WE population appears to be endemic to Western Europe. Both populations evolved in response to population-specific selection forces, resulting in distinct localized adaptations that allowed them to migrate into their environmental niche. The detection of positive selection in genes with protein/zinc ion binding domains, transcription factors and in genes encoding proteins involved in transmembrane transport highlights their important role in driving evolutionary novelty that allow F. graminearum to increase adaptation to the host and/or environment. F. graminearum also maintained distinct sets of accessory genes showing population-specific conservation. Among them, genes involved in host invasion and virulence such as those encoding proteins with high homology to tannase/feruloyl esterase and genes encoding proteins with functions related to oxidation-reduction were mostly found in the WE population. Our findings shed light on genetic features related to microevolutionary divergence of F. graminearum and reveal relevant genes for further functional research aiming at better control of this pathogen.