Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.ope

Effects of body position and clinical signs on L7-S1 intervertebral foraminal area and lumbosacral angle in dogs with lumbosacral disease as measured via computed tomography

Objective—To measure effects of dog position on L7-S1 intervertebral foraminal area and lumbosacral (LS) angle by means of computed tomography (CT) and determine whether changes in values between positions are associated with clinical signs in dogs with LS disease. Animals—86 dogs examined via a positional CT protocol that included flexion and extension scans of L7-S1. Procedures—Archived CT images and medical records were reviewed. Included dogs had good-quality flexion and extension CT scans of L7-S1 and no evidence of fractures, neoplasia, or previous LS surgery. One person who was unaware of CT findings recorded clinical status with regard to 3 signs of LS disease (right or left hind limb lameness and LS pain) at the time of CT evaluation. One person who was unaware of clinical findings measured L7-S1 foraminal areas and LS angles, with the aid of an image-analysis workstation and reformatted parasagittal planar CT images. Results—Intraobserver variation for measurements of L7-S1 foraminal area ranged from 6.4% to 6.6%. Mean foraminal area and LS angle were significantly smaller when vertebral columns were extended versus flexed. Percentage positional change in L7-S1 foraminal area or LS angle was not significantly different among dogs with versus without each clinical sign. There was a significant correlation between percentage positional change in L7-S1 foraminal area and LS angle in dogs with versus without ipsilateral hind limb lameness and LS pain. Conclusions and Clinical Relevance—Positional CT is a feasible technique for quantifying dynamic changes in L7-S1 intervertebral foraminal morphology in dogs with LS disease.Jeryl C. Jones, Sarah E. Davies, Stephen R. Werre, Kristen L. Shackelfor