Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma.

Comprehensive gene screening with transposons is a novel procedure for the systematic identification of resistant genes. The present study aimed to use this technique to identify candidate radioresistant genes in esophageal squamous cell carcinoma. A transposon is a base sequence that can translocate to another location in the genome at random. By inserting the cytomegalovirus promotor as a transcriptional activator in the transposon, the following gene in the new location becomes overexpressed and the gene located at the transposon insertion site is downregulated. Consequently, various transposon-tagged cells, which have differentially overexpressed or downregulated genes using the transposon method can be obtained. Following the irradiation of transposon-tagged cells, candidate radioresistant genes can be selected in order to detect the location of the transposon in the cells that have survived. A total of 11 genes were detected as candidate radioresistant genes. Cytochrome c oxidase 1 (MT-CO1), an enzyme involved in apoptosis through the activation of the caspase cascade, was one of the candidate genes identified. The relative expression level of MT-CO1 was 0.12 in MT-CO1-downregulated cells which was significantly lower compared with the expression level in parent TE4 cells (P<0.001). The survival rate was 28.7% in MT-CO1-downregulated cells and 10.5% in parent TE4 cells 9 days following 5-Gy irradiation. The activity of cytochrome c and caspase-3 following irradiation was significantly lower in the MT-CO1-downregulated radioresistant cells compared with in TE4 cells. In conclusion, the novel gene screening technique demonstrated to be useful for detecting candidate radioresistant genes in esophageal squamous cell carcinoma. The results of the present study revealed that the downregulation of MT-CO1 induced radioresistance occurs by inhibiting the activation of the caspase cascade in radioresistant esophageal cancer cells.

A Prospective Randomized Trial of Enteral Nutrition After Thoracoscopic Esophagectomy for Esophageal Cancer.

BACKGROUND: Several studies have reported that postoperative enteral nutrition (EN) reduced complications and decreased weight loss and hospital stay periods; however, the majority of patients analyzed in these studies underwent open thoracic surgery. No studies have been conducted regarding EN in patients after thoracoscopic esophagectomy as a less invasive surgery. The aim of this study was to investigate the efficacy of EN after thoracoscopic esophagectomy. METHODS: Fifty patients who underwent thoracoscopic esophagectomy for esophageal cancer were divided into two groups: parenteral nutrition (PN; n = 25) and EN (n = 25). The rate of weight loss at postoperative day (POD) 14, levels of prealbumin at POD 10, postoperative complications until POD 14, and other perioperative data were collected for each group. RESULTS: This study analyzed data for 47 patients. The rate of weight loss at POD 14 was significantly lower in the EN group (3.0 ± 3.2 %) than in the PN group (5.1 ± 3.7 %; p = 0.020). Prealbumin levels were 21.0 ± 7.5 mg/dL in the PN group and 18.4 ± 5.8 mg/dL in the EN group at POD 10, with no significant differences between the groups. However, the incidence of postoperative pneumonia was higher in the PN group (30.4 %) than in the EN group (12.5 %). CONCLUSIONS: EN could suppress weight loss and reduce the incidence of pneumonia after thoracoscopic esophagectomy.

Postoperative hyperbilirubinemia suggests the occurrence of complications after esophagectomy for esophageal cancer.

BACKGROUND: Serum bilirubin levels frequently increase after esophagectomy for esophageal cancer. Several studies have reported hyperbilirubinemia in patients with postoperative complications. We aimed to perform a detailed large-scale analysis to clarify this association. METHODS: We compared postoperative serum bilirubin levels of 200 patients with esophageal cancer who underwent esophagectomy, with and without postoperative complications, from January 2008 to July 2013 at Keio University Hospital, Tokyo, Japan. We also analyzed other risk factors for postoperative hyperbilirubinemia by univariate and multivariate analyses in an attempt to determine the mechanism of postoperative hyperbilirubinemia. RESULTS: Hyperbilirubinemia (total bilirubin >2.0 mg/dL) occurred in 71 patients (35.5 %). The mean total bilirubin peak level was 1.5 mg/dL in patients without complications, 2.0 mg/dL in those with at least one complication, 2.1 mg/dL in those with pneumonia, and 2.3 mg/dL in those with anastomotic leakage. Bilirubin levels were significantly higher in each complication group than in the non-complication group (p < 0.05 for all). Risk factors of postoperative hyperbilirubinemia by univariate analysis were the preoperative bilirubin level, video-assisted thoracoscopic surgery, three-field lymph node dissection, thoracic duct resection, prolonged surgical duration, severe complications (Clavien-Dindo grade ≥3), and severe anastomotic leakage (Clavien-Dindo grade ≥3). In contrast, the pT factor and postoperative enteral nutrition were negatively associated with postoperative hyperbilirubinemia. Risk factors by multivariate analysis were the preoperative bilirubin level, prolonged surgical duration, severe complications, and postoperative enteral nutrition. CONCLUSIONS: Although various factors impact postoperative hyperbilirubinemia, postoperative complications were most significantly associated with postoperative hyperbilirubinemia. Patients with postoperative hyperbilirubinemia after esophagectomy must be managed more carefully because unnoticed complications may be associated with hyperbilirubinemia.