Measurement variability of liver metastases from neuroendocrine tumors on different magnetic resonance imaging sequences

International audiencePURPOSE: To assess dimension measurement variability of liver metastases from neuroendocrine tumors (LMNET) on different magnetic resonance imaging (MRI) sequences.MATERIAL AND METHODS: In this institutional review board-approved retrospective study from January 2011 to December 2012, all liver MRI examinations performed at our department in patients with at least one measurable LMNET according to response evaluation criteria in solid tumors (RECIST1.1) were included. Up to two lesions were selected on T2-weighted MR images. Three reviewers independently measured long axes of 135 hepatic metastases in 30 patients (16 men, 14 women, mean age 61±11.4 (SD) years; range 28-78 years), during two separate reading sessions, on T2-weighted, diffusion-weighted MRI (DWI) (b; 50, 400, 800 s/mm2) and arterial, portal and late phases after intravenous administration of a gadolinium chelate. Intraclass-correlation coefficients and Bland-Altman plots were used to assess intra-and interobserver variability.RESULTS: Intra- and interobserver agreements ranged between 0.87-0.98, and 0.88-0.97, respectively. Intersequence agreements ranged between 0.92 [95%CI: 0.82-0.98] and 0.98 [95%CI: 0.93-0.99]. 95% limits of agreement for measurements were -10.2%,+8.9% for DWI (b=50s/mm2) versus -21.9%,+24.2% and -15.8,+17.2% for arterial and portal phases, respectively.CONCLUSION: An increase<9% in measurement and a decrease of -10% on DWI should not be considered as true changes, with 95% confidence, versus 24% and -22% on arterial and 17%, -16% on portal phases, respectively. DWI might thus be the most reliable MR sequence for monitoring size variations of LMNETs

Amino Acid Substitutions in Polymerase Basic Protein 2 Gene Contribute to the Pathogenicity of the Novel A/H7N9 Influenza Virus in Mammalian Hosts

A novel avian-origin influenza A/H7N9 virus emerged in 2013 to cause more than 130 cases of zoonotic human disease, with an overall case fatality rate of around 30% in cases detected. It has been shown that an E-to-K amino acid change at residue 627 of polymerase basic protein 2 (PB2) occurred frequently in the H7N9 isolates obtained from humans but not in viruses isolated from poultry. Although this mutation has been reported to confer increased mammalian pathogenicity in other avian influenza subtypes, it has not been experimentally investigated in the H7N9 virus. In this study, we determined the contribution of PB2-E627K in H7N9 virus to its pathogenicity in mammalian hosts. In addition, the compensatory role of the PB2 mutations T271A, Q591K, and D701N in H7N9 virus was investigated. We characterized the activity of polymerase complexes with these PB2 mutations and found that they enhance the polymerase activity in human 293T cells. The rescued mutants enhanced growth in mammalian cells in vitro. Mice infected with the H7N9 mutant containing the avian signature protein PB2-627E showed a marked decrease in disease severity (weight loss) and pathology compared to mice infected with the wild-type strain (PB2-627K) or other PB2 mutants. Also, mutants with PB2-627E showed lower virus replication and proinflammatory cytokine responses in the lungs of the virus-infected mice, which may contribute to pathogenicity. Our results suggest that these amino acid substitutions contribute to mouse pathogenicity and mammalian adaptation