Use of gene expression profiling to identify candidate genes for pretherapeutic patient classification in acute appendicitis.

BACKGROUND: Phlegmonous and gangrenous appendicitis represent independent pathophysiological entities with different clinical courses ranging from spontaneous resolution to septic disease. However, reliable predictive methods for these clinical phenotypes have not yet been established. In an attempt to provide pathophysiological insights into the matter, a genomewide gene expression analysis was undertaken in patients with acute appendicitis. METHODS: Peripheral blood mononuclear cells were isolated and, after histological confirmation of PA or GA, analysed for genomewide gene expression profiling using RNA microarray technology and subsequent pathway analysis. RESULTS: Samples from 29 patients aged 7-17 years were included. Genomewide gene expression analysis was performed on 13 samples of phlegmonous and 16 of gangrenous appendicitis. From a total of 56 666 genes, 3594 were significantly differently expressed. Distinct interaction between T and B cells in the phlegmonous appendicitis group was suggested by overexpression of T cell receptor α and ß subunits, CD2, CD3, MHC II, CD40L, and the B cell markers CD72 and CD79, indicating an antiviral mechanism. In the gangrenous appendicitis group, expression of genes delineating antibacterial mechanisms was found. CONCLUSION: These results provide evidence for different and independent gene expression in phlegmonous and gangrenous appendicitis in general, but also suggest distinct immunological patterns for the respective entities. In particular, the findings are compatible with previous evidence of spontaneous resolution in phlegmonous and progressive disease in gangrenous appendicitis.

Eosinophilia in pediatric uncomplicated appendicitis is a time stable pattern.

PURPOSE: We have recently shown that uncomplicated phlegmonous appendicitis is characterized by independent inflammatory patterns based on significant eosinophilia in children aged 7-17 years. However, clinical decision-making based on inflammatory values is not easy, especially due to the dynamics of inflammation over time. The present study was performed to evaluate the basic distinguishability of the inflammatory entities by laboratory values over time based on an extended patient number with children aged 0-17 years. METHODS: All patients aged 0-17 years, who underwent appendectomy from January 2008 until June 2016, were retrospectively reviewed. Special attention was paid to cellular subpopulations within full blood counts within compartments of time (onset of symptoms - blood sampling): 0-12 , > 12-24 , > 24-36 , > 36-48 , > 48-72 , > 72 h. RESULTS: 1041 appendectomies were included in the study. The inflammatory course in patients with complicated appendicitis (n = 369) was characterized by continuously increased mean leukocytes, neutrophil and monocyte counts compared with patients with phlegmonous appendicitis (n = 489). In contrast, continuous relative eosinophilia was found in uncomplicated appendicitis within the inflammatory process. In cases of negative appendectomies (n = 183), again, distinct independent inflammatory patterns were found. CONCLUSION: Eosinophilia is a constant and independent pattern in children with uncomplicated appendicitis, which, thus, can be distinguished throughout the inflammatory process.