In the present study, we assessed the involvement of hepatocyte growth factor (HGF)/c-Met signalling with vascular endothelial cell growth factor (VEGF) and hypoxia inducible factor (HIF)-1α expression in the downstream pathways phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) in CT26 cells, to determine the mechanisms of the potent anti-angiogenic effect of NK4. We established genetically modified CT26 cells to produce NK4 (CT26-NK4). VEGF expression in subcutaneous CT26 tumours in vivo and in culture supernatants in vitro was determined by ELISA. HIF-1α expression in nuclear extracts was evaluated by western blot analysis. VEGF and HIF-1α mRNA levels were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR). The DNA binding activity of HIF-1α was evaluated using an HIF-1α transcription factor assay kit. Our results demonstrated that VEGF expression was reduced in homografts of CT26-NK4 cells, compared to those of the control cells. In vitro, VEGF expression, which was induced by HGF, was inhibited by anti-HGF antibody, NK4 and by kinase inhibitors (PI3K, LY294002; MAPK, PD98059; and STAT3, Stattic). HGF‑induced HIF‑1α transcriptional activity was also inhibited by the kinase inhibitors. Real-time RT-PCR demonstrated that HGF‑induced HIF‑1α mRNA expression was not inhibited by LY294002 and PD98059, but was inhibited by Stattic. These data suggest that the PI3K/Akt, MAPK and STAT3 pathways, downstream of HGF/c‑Met signalling, are involved in the regulation of VEGF expression in CT26 cells. HGF/c‑Met signalling may be a promising target for anti-angiogenic strategies.

Background/Aims: Bile leakage frequently causes major complications after hepatic resection. We investigated perioperative risk factors and management of postoperative bile leakage after hepatic resection without extrahepatic biliary resection and reconstruction. Methods: We included 247 consecutive patients who underwent elective hepatic resection without bilioenteric anastomosis at our institution between 2002 and 2009. Perioperative risk factors, including patient and surgical variables, were evaluated using univariate and logistic regression analyses. Results: Postoperative bile leakage occurred in 26 patients (10.5%). The surgical drain was retained in 6 patients (23%); 9 (35%) underwent drain salvage and 11 (42%) underwent percutaneous puncture under computed tomography or ultrasound guidance. Eight patients underwent endoscopic nasobiliary drainage (ENBD) for postoperative bile leakage, and bile leakage healed at a median interval of 19.5 days after ENBD. By univariate analysis, postoperative bile leakage was associated with central bisectionectomy, surgical time and intraoperative blood loss. Logistic regression analysis identified central bisectionectomy as an independent risk factor for postoperative bile leakage (p = 0.0003, odds ratio 16.724). Conclusion: Meticulous procedures are necessary during parenchymal hepatic resection, especially during central bisectionectomy. Drain management should be precise in the case of postoperative bile leakage. We believe ENBD may rapidly cure postoperative major bile leakage.

Abstract. The development of surgical and postoperative management techniques has improved the treatment outcomes of esophageal cancer resection. However, respiratory morbidity is still the most frequent complication after esophagectomy. The objective of the present study was to identify risk factors for respiratory complications following resection for esophageal cancer. This study included 96 patients with esophageal cancer who had undergone esophagectomy with lymph node dissection. The patients were divided into 2 groups according to the presence (20 patients, 17 had pneumonia and 3 had acute respiratory distress syndrome) or absence (76 patients) of postoperative respiratory complications (PRC). The two groups were compared with respect to their preoperative clinical variables, such as age, body mass index, smoking history, serum albumin, serum C-reactive protein (CRP), number of lymphocytes, %VC, FEV1.0% and FEV1.0. Furthermore, multiple logistic regression analyses were used to estimate relative risk factors for respiratory complications. Results of the univariate analysis showed that smoking history (+/-, patients with PRC, 19/1 and without PRC, 53/23), serum CRP (≥1.0 mg/ dl/<1.0 mg/dl, patients with PRC, 6/14 and without PRC, 6/70) and FEV1.0% (≥60%/<60%, patients with PRC, 16/4 and without PRC, 73/3) were significantly different between the two groups. Multiple logistic regression analysis showed that FEV1.0% was the strongest predictor of PRC. FEV1.0%, serum CRP and smoking history are reliable predictors of the risk of respiratory complications following esophageal cancer resection. For patients with these factors, perioperative management for the prevention of postoperative respiratory complications should be considered.

In summary, our procedure using PGA felt with fibrin sealant may reduce the risk of severe POPF.

Our results suggested that the most dismal CRC harbors three definite vectors that may represent the strongest phenotype of putative systemic immune (CA19-9), distant metastasis (extent of liver metastases), and local progression (peritoneal dissemination).