BACKGROUND: Cytokeratins (CKs) are structural marker proteins specific for epithelial cells. However, recent studies indicate their involvement in cancer progression. METHODS: We evaluated CK18 and its filament partner, CK8 expression, by immunohistochemistry in 210 resected specimens from patients with oesophageal squamous cell carcinoma (OSCC). We also analysed the relationship between their expression and various clinicopathological parameters including prognosis. RESULTS: Neither CK18 nor CK8 was expressed in non-cancerous squamous epithelium whereas proper oesophageal glands expressed both CKs. Ninety (42.9%) tumours were CK18 positive and 85 (40.5%) CK8 positive, and the concordance rate for immunohistochemical classification for CK18 and CK8 was 82.4%. CK18 expression correlated with poorly differentiated tumours, use of neo-adjuvant chemotherapy, and advanced stage. Prognosis of patients with CK18-positive tumours was poorer than that of patients with negative OSCC (Po0.001). A similar trend was noted for CK8 expression. Multivariate analysis identified pT (P ¼ 0.020), pN number (P ¼ 0.001), and CK18 expression (P ¼ 0.004) as independent prognostic factors. CK18 expression in 83 pretreatment biopsy specimens was detected in 47 cases (56.6%) and also correlated with prognosis (P ¼ 0.045). CONCLUSION: CK18/CK8 expression correlated with progression of OSCC. The significant correlation with prognosis and stable expression in biopsy specimen suggest usefulness of CK18 in selection of treatment strategies for OSCC.
Gene expression profiling is a valuable tool for identifying differentially expressed genes in studies of disease subtype and patient outcome for various cancers. However, it remains difficult to assign biological significance to the vast number of genes. There is an increasing awareness of gene expression profile as an important part of the contextual molecular network at play in complex biological processes such as cancer initiation and progression. This study analysed the transcriptional profiles commonly activated at different stages of gastric cancers using an integrated approach combining gene expression profiling of 222 human tissues and gene regulatory dynamic mapping. We focused on an inferred core network with
CDKN1A
(
p21
WAF1/CIP1
) as the hub, and extracted seven candidates for gastric carcinogenesis (
MMP7, SPARC, SOD2, INHBA, IGFBP7, NEK6, LUM
). They were classified into two groups based on the correlation between expression level and stage. The seven genes were commonly activated and their expression levels tended to increase as disease progressed. NEK6 and INHBA are particularly promising candidate genes overexpressed at the protein level, as confirmed by immunohistochemistry and western blotting. This integrated approach could help to identify candidate players in gastric carcinogenesis and progression. These genes are potential markers of gastric cancer regardless of stage.
Although studies have shown that early oral feeding after abdominal surgery is feasible, the optimal dietary schedule has not been established. This study was conducted prospectively to compare the clinical outcome of patient-controlled dietary schedule with that of conventional dietary schedule after gastric resection for early cancer. Patients in the patient-controlled diet (PC) group (n = 53) received a solid diet on demand; patients in the conventional regimen (CR) group (n = 50) received a solid diet from postoperative day (POD) 10. All patients underwent distal gastrectomy for early gastric cancer. A liquid diet was tolerated by the PC group on POD 2, and a solid diet was taken on POD 6 after gastrectomy, earlier than in the CR group. The postoperative hospital stay was 18.5 +/- 5.9 days (10-40) in the PC group, versus 21.7 +/- 8.8 days (14-57) in the CR group (p = 0.02). Patients in the PC group had a higher daily oral intake of calories on POD 10 than those in the CR group (p = 0.02). Changes in body weight and serum albumin during the postoperative period and after discharge, and the incidence of complications and variances from clinical pathways did not show significant differences between the two groups. The PC schedule was feasible after distal gastrectomy for early gastric cancer. It improved the clinical outcome, with a shorter postoperative hospital stay and a higher oral energy intake on early phase, compared with the CR schedule. Moreover, the PC approach was useful for establishing the optimal dietary schedule and improving the clinical pathway.
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