Prognostic factors affecting survival after surgical resection of gastrointestinal stromal tumours: a two-unit experience over 10 years

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) tract which has only been recently described based on their specific immunohistochemistry and the presence of particular KIT-related mutations which potentially make them targets for tyrosine kinase inhibition. METHODS: Sixty-one patients (29 M; 32 F, median age 60 years; range: 23–86 years) between June 1994 and March 2005, were analyzed from two allied institutions. Patient, tumour, and treatment variables were analyzed to identify factors affecting survival. RESULTS: Of the 61 patients, 55 (90%) underwent complete surgical resection of macroscopic disease. The 5-year overall survival (OS) rate in the 61 patients was 88% and the 5-year disease-free survival (DFS) in the 55 cases completely resected was 75%. Univariate analysis revealed that R0 resection was strongly associated with a better OSrate (p < 0.0001). Likewise, univariate analysis also showed high mitotic count of > 10 mitoses/per 50 HPF was a significant variable in worse prognosis for OS (≤ 10 mitoses/per 50 HPF 95% 5-year OS vs. > 10 mitoses/per 50 HPF 74% 5-year OS, respectively; p = 0.013). On subsequent multivariate analysis, only high mitotic count remained as a significant negative prognostic variable for OS (p = 0.029). Among patients resected for cure, there were 8 recurrences during follow-up. The mean time to recurrence was 21 ± 10 months (range: 4–36 months). Univariate analysis revealed that mitotic count of > 10 mitoses per 50 high power fields, intratumoural necrosis, and pathological tumour size (> 10 cm in maximal diameter) significantly correlated with DFS (p = 0.006, 0.002 and 0.02, respectively), with tumour necrosis and high mitotic count remaining as independent predictive variables affecting prognosis on subsequent multivariate analysis. CONCLUSION: Most GISTs are resectable with survival principally dependent upon mitotic count and completeness of resection. Future metabolic and genetic analyses will define the role of and resistance to induction or postoperative adjuvant targeted kinase inhibition therapy

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Characterization of Pax3 and Sox10 transgenic Xenopus laevis embryos as tools to study neural crest development

The neural crest is a multipotent population of cells that originates a variety of cell types. Many animal models are used to study neural crest induction, migration and differentiation, with amphibians and birds being the most widely used systems. A major technological advance to study neural crest development in mouse, chick and zebrafish has been the generation of transgenic animals in which neural crest specific enhancers/promoters drive the expression of either fluorescent proteins for use as lineage tracers, or modified genes for use in functional studies. Unfortunately, no such transgenic animals currently exist for the amphibians Xenopus laevis and tropicalis, key model systems for studying neural crest development. Here we describe the generation and characterization of two transgenic Xenopus laevis lines, Pax3-GFP and Sox10-GFP, in which GFP is expressed in the pre-migratory and migratory neural crest, respectively. We show that Pax3-GFP could be a powerful tool to study neural crest induction, whereas Sox10-GFP could be used in the study of neural crest migration in living embryos