The progression of Barrett's esophagus to esophageal adenocarcinoma is often characterized by the accumulation of genetic abnormalities. The goal was to evaluate the copy number alterations of several oncogene loci, including 7p12 [epidermal growth factor receptor (EGFR)], 8q24 (c-myc), and 20q13 in the sequence of no dysplasia -dysplasia -adenocarcinoma of Barrett's esophagus. Fluorescence in situ hybridization with DNA probes for the centromeric region of chromosome 7 and the locus-specific regions of 7p12 (EGFR), 8q24 (c-myc), and 20q13 was applied on 99 brush cytology specimens of patients with Barrett's esophagus with different stages of dysplasia or esophageal adenocarcinoma. Gains (3-4 copies) of chromosome 17, 8q24 (c-myc), and 20q.13 loci were found in the low frequencies in nondysplastic Barrett's esophagus. Their frequencies increased with the stage of dysplasia and reached a high incidence in esophageal adenocarcinoma.Amplification (>4 copies) of at least 1 of the loci was observed in 14% of high-grade dysplasia and increased to 50% in esophageal adenocarcinoma (P = 0.015). The most frequently amplified locus was c-myc (18%), followed by 20q13 (13%) and EGFR (11%) in the highgrade dysplasia/esophageal adenocarcinoma cases. High amplification levels (>10 copies) of the loci were more frequent in esophageal adenocarcinoma (72%) compared with high-grade dysplasia (20%; P = 0.049). Amplifications of the c-myc, EGFR, and 20q12 loci may serve as diagnostic markers to identify patients with Barrett's esophagus with high-grade dysplasia or esophageal adenocarcinoma. Gains of the loci might be of value as prognostic markers because they are already present in nondysplasia cases and may precede the later event of the amplification as observed in high-grade dysplasia and esophageal adenocarcinoma. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1380 -5)

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IL‐12(p70), a heterodimer composed of two subunits (p35 and p40), is a key cytokine for Th1 mediated inflammatory responses. We dissected the role of IL‐12 in the development of 2,4,6‐trinitrobenzene sulfonic acid (TNBS)‐induced colitis by studying mice deficient in IL‐12p40, IL‐12p35, or IL‐12Rβ1. TNBS‐treated IL‐12Rβ1–/– and IL‐12p35–/– mice developed only a mild disease associated with low level IL‐18 expression in IL‐12p35–/– mice. In contrast, IL‐12p40–/– mice developed more severe colitis than wild‐type mice associated with high level colonic IL‐18 expression. Administration of IL‐12p40 neutralizing mononuclear antibody dramatically increased pathology in IL‐12p35–/– mice similar to disease scored in IL‐12p40–/– mice. Numbers of IFN‐γ‐producing cells infiltrating the lamina propria were comparably augmented in the different groups of IL‐12‐mutant and wild‐type mice. These results demonstrate that IL‐12p40, in contrast to IL‐12p70, inhibits TNBS‐induced colitis and IL‐18 expression independent of IFN‐γ.

Bevacizumab added to oxaliplatin-based CTx may protect against moderate sinusoidal dilatation without significantly influencing morbidity. Neither duration of oxaliplatin-based CTx nor the time interval between cessation of oxaliplatin-based CTx and surgery were associated with postoperative complications.

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