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Background/purpose: The aim of this study is to examine the effects of biliary drainage on hepatic microcirculation and Kupffer cell activity in the liver with obstructive jaundice. Methods: Common bile duct ligation and division was performed on C57BL/6 mice to induce obstructive jaundice. Seven or 14 days after surgery, some mice underwent biliary drainage. Three days after biliary drainage, sinusoidal perfusion, leukocyte rolling and sticking in the postsinusoidal venules, and the diameters of sinusoids containing blood flow were evaluated using intravital microscopy. Kupffer cell phagocytic activity was estimated as the ratio of Kupffer cells that phagocytosed fluorescent-labeled particles to sinusoids containing blood flow. Results: Sinusoidal perfusion after biliary drainage was significantly increased compared with that in livers with obstructive jaundice, but remained decreased compared with controls. Although the number of rolling leukocytes and sticking leukocytes was significantly decreased, the diameters of sinusoids remained reduced, associated with an increase in Kupffer cell phagocytic activity compared with controls even after biliary drainage. Conclusions: Leukocyte-endothelial cell interaction is ameliorated but sinusoids remain narrowed due to swelling of activated Kupffer cells; this might cause deterioration of hepatic microcirculation during the early phase of biliary drainage. [ABSTRACT FROM AUTHOR]

Many authors at high-volume centers all over the world have reported improved outcomes of hilar cholangiocarcinoma by several aggressive surgical approaches such as extended hepatic resection, combined vascular resection, and hepatopancreaticoduodenectomy in recent years. There has been great progress in the surgical treatment of hilar cholangiocarcinoma with these previous efforts by aggressive hepatobiliary surgeons. In particular, surgical techniques, diagnostic modalities, and perioperative management have been remarkably improved as compared with before. Herein we report the surgical outcome for both hilar cholangiocarcinoma of Bismuth types II, III, and IV and intrahepatic cholangiocarcinoma involving the hepatic duct confluence during the recent 8-year period between 2001 and 2008 at our institution, the Department of General Surgery at Chiba University. From our recent experienced results, it can be concluded that the surgical strategy for hilar cholangiocarcinoma has been improved remarkably, and major surgical hepatectomy can be done with relative safety, and these aggressive surgical approaches, including combined vascular resection, may be warranted for the surgical treatment of hilar cholangiocarcinoma. However, the adoption of new innovative therapeutic approaches might be required for further improvement of surgical outcome of hilar cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Tumors with copious mucin production within the intra- or extrahepatic bile ducts have been reported as mucin-producing bile duct tumors (MPBTs). Because mucin produced by these tumors causes recurrent cholangitis and obstructive jaundice, surgical resection should be indicated even if these tumors are regarded as benign. In order to choose the appropriate surgical procedure, exact preoperative assessment of tumor location and cancer extension is important, especially evaluation of the extent of superficial spreading through cholangioscopic observation and biopsy. In principle, MPBTs should be resected in a manner similar to that employed for other types of bile duct carcinomas. That is, major hepatectomy with or without extrahepatic bile duct resection or pancreaticoduodenectomy should be chosen as the surgical procedure, and intraoperative frozen section at the stumps of the bile duct is essential. On the other hand, when precise diagnosis is completed preoperatively and the lesion is diagnosed as adenoma or carcinoma with invasion confined to the ductal wall and limited superficial spreading, limited resections preserving organ functions as much as possible can be considered as a choice among surgical procedures. All ten patients with MPBT resected at our institution according to these strategies are still alive without tumor recurrence, with a median survival of 48.0 months. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigates the effect of adjuvant chemotherapy with uracil/tegafur (UFT) and gemcitabine GEM against GEM alone in patients with resected pancreatic cancer. It reveals that GEM-based adjuvant chemotherapy given postoperatively was safe and well tolerated by patients. However, the use of UFT with GEM did not show improvement for disease-free survival. (DFS) as compared to using GEM alone.

Background and Aim: Nonoperative management of cases of adhesive intestinal obstruction would be ideal, especially for patients who have recently undergone surgery to relieve the same condition. We aimed to examine whether hyperbaric oxygen (HBO) therapy might have therapeutic potential for the treatment of postoperative paralytic ileus and recurrent adhesive intestinal obstruction soon after surgery, to relieve adhesive intestinal obstruction, because of its unique mechanisms in these contexts. Methods: A total of 133 patients were enrolled in the present study. We examined non– per os periods, hospital stay, and clinical course according to the postoperative course of the 133 patients. Results: After surgical intervention, 75 patients left the hospital without morbidity. Nineteen patients were successfully administered prophylactic HBO therapy to facilitate intestinal motility and to prevent paralytic ileus. The remaining 39 patients suffered from postoperative paralytic ileus or early recurrence of obstruction during the same hospitalization period. The patients who underwent prophylactic HBO therapy had significantly shorter non– per os periods and hospital stays after surgery than those who were not initially given HBO therapy ( P < 0.05). Similarly, there were significant differences in duration of hospital stay after surgery between patients with HBO therapy as treatment and those who received other conservative therapies ( P < 0.05). Conclusions: HBO therapy may have a prophylactic effect on postoperative paralytic ileus and may be of therapeutic benefit in the management of early recurrent adhesive intestinal obstruction following surgery to relieve adhesive intestinal obstruction. [ABSTRACT FROM AUTHOR]

Background and Aim: Hepatocellular carcinoma (HCC) is characteristically a hypervascular tumor and its progression is known to be closely related to angiogenesis. In this study, we investigated angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) levels in the hepatic vein draining from HCC, as well as in the peripheral vein, to evaluate their relation to clinicopathological features and prognosis. Methods: To obtain hepatic venous blood samples, a catheter was placed into the main branch of the hepatic vein draining from HCC in 21 patients. The Ang-2 and VEGF levels in both the hepatic and peripheral veins were investigated. Furthermore, Ang-2 mRNA expression in surgically resected HCC was evaluated by quantitative reverse-transcription polymerase chain reaction (RT-PCR), as well as microvessel density (MVD) by CD34 immunostaining. Results: Ang-2 levels in the hepatic vein significantly correlated with Ang-2 mRNA expression in HCC, but Ang-2 levels in the peripheral vein did not correlate. Furthermore, a significant correlation was found between hepatic venous Ang-2 and MVD levels, whereas there was no significant correlation with hepatic venous VEGF levels. When hepatic venous Ang-2 levels were compared with clinicopathological features, a significant relationship was found between high Ang-2 levels and portal vein invasion. The survival for patients in the high hepatic venous Ang-2 group was significantly poorer when compared with the low group. Conclusion: Preoperative hepatic venous Ang-2 levels may be a good predictor for portal vein invasion and also prognosis in patients with HCC. [ABSTRACT FROM AUTHOR]

Background and Aim: Hepatocellular carcinoma is one of the most common cancers. α-Fetoprotein is strongly expressed in most patients with hepatocellular carcinoma, and high levels of α-fetoprotein expression have been reported as an independent prognostic factor. However, there have been few reports on the reasons for poor prognosis. Methods: We analyzed the correlation between serum α-fetoprotein levels and clinicopathological findings in 37 hepatocellular carcinoma patients undergoing curative surgery. α-Fetoprotein mRNA expression in tissue samples was analyzed by quantitative reverse transcription–polymerase chain reaction (RT-PCR), while protein expression was assessed by immunohistochemistry. To assess the mechanistic correlations between α-fetoprotein and tumor progression, we further analyzed cell proliferation (Ki-67), angiogenesis (CD34), and apoptosis (TdT-mediated dUTP-biotin nick end labeling [TUNEL] assay). Results: Post-operative serum α-fetoprotein levels were correlated with disease-free and overall survival, and were an independent prognostic factor for survival. α-Fetoprotein expression, as assessed by immunohistochemistry, was strong and heterogeneous in hepatocellular carcinoma. Control livers did not express α-fetoprotein and there was weak expression of α-fetoprotein in adjacent regions in hepatocellular carcinoma patients. The Ki-67 labeling index in the high serum α-fetoprotein cases was significantly higher than in α-fetoprotein-negative cases ( P = 0.042). The α-fetoprotein-positive cases also showed a significantly higher microvessel density than α-fetoprotein-negative cases ( P = 0.035), whereas hepatocellular carcinoma without α-fetoprotein overexpression had a higher apoptotic index when compared to hepatocellular carcinoma with α-fetoprotein overexpression ( P = 0.033). Conclusion: These results indicate that the poor prognosis associated with high α-fetoprotein is due to high cell proliferation, high angiogenesis, and low apoptosis. [ABSTRACT FROM AUTHOR]

A transcriptional factor, CCAAT/enhancer binding protein-β (C/EBP-β), regulates a variety of cell functions in normal and neoplastic cells. Although the involvement of C/EBP-β in metastasis has been demonstrated clinicopathologically in several types of human cancer, the mechanism by which it functions during the multistep process of metastasis remains largely unknown. We investigated the role of C/EBP-β in the intravascular step of hematogenous metastasis in a rat pancreatic tumor cell line, AR42J-B13, as this step profoundly affects metastatic efficiency. C/EBP-β-transfected AR42J-B13 (βB13) cells acquired considerable resistance against serum toxicity, which was primarily mediated by apoptosis in vitro. Upregulated expression of Bcl-2 and Bcl-xL was seen in βB13 cells. Enhanced early survival of intraportally injected βB13 cells in the BALB/c nu/nu male mice liver, detected by the mRNA of a vector-specific gene, was observed. Nick-end labeling analysis of the tumor-injected liver revealed significantly lower rates of apoptosis among intravascular βB13 tumor cells than among empty vector-transfected AR42J-B13 (mB13) cells. Finally, intrasplenically injected βB13 cells established a larger number of colonies in the liver than did the mB13 cells. These findings suggest that C/EBP-β may enhance hematogenous metastasis and its antiapoptotic effects may promote the survival of intravascular tumor cells. ( Cancer Sci 2007; 98: 1706–1713) [ABSTRACT FROM AUTHOR]

Investigates anti-inflammatory response in patients with obstructive jaundice caused by biliary malignancy. Increase of plasma concentrations of the anti-inflammatory mediators among jaundiced patients; Occurrence of a systemic inflammatory response by lipopolysaccharide; Downregulation of the protective immunity by interleukin-10.

AbstractBackground: It has been suggested that human hepatocyte growth factor (hHGF) maintains the growth and viability of hepatocytes and biliary epithelial cells. The purpose of this study was to determine plasma hHGF concentrations in patients with obstructive jaundice and to correlate these findings with clinical outcome. Methods: The study included 22 patients who had biliary obstruction and underwent percutaneous transhepatic biliary drainage. The plasma concentrations of hHGF, standard liver function tests, daily bile flow and the half-life of serum total bilirubin were measured following the drainage. Results: Plasma hHGF concentrations were significantly higher in patients with biliary obstruction compared with a control group (P < 0.01). The plasma hHGF concentrations correlated with white cell count, prothrombin time and bilirubin half-life (P < 0.05), but not with the values from other liver function tests. Seven patients who died within 3 months after biliary drainage had significantly higher concentrations of plasma hHGF than the 15 patients who survived for at least 3 months (P < 0.05). The patients who experienced a poor outcome also had lower bile flows and prolonged bilirubin half-lives compared with the survivors (P < 0.05). The plasma hHGF concentrations decreased significantly after biliary drainage in the survivors (P < 0.01), but not in the patients with a poor outcome. Conclusions: These results suggest that systemic inflammation and the hepatic dysfunction caused by obstructive jaundice cause an increase in the plasma concentrations of hHGF. In addition, the plasma concentrations of hHGF may be a predictor of poor outcome in jaundiced patients. [ABSTRACT FROM AUTHOR]