Hideaki Miyaso

Obstructive jaundice increases sensitivity to lipopolysaccharide via TLR4 upregulation: Possible involvement in gut-derived hepatocyte growth factor-protection of hepatocytes

Background:  Patients with obstructive jaundice are prone to sepsis after biliary tract surgery. The present study was designed to determine the effect of biliary obstruction on cytokine responses to lipopolysaccharide (LPS).

Failure of the gut barrier system enhances liver injury in rats: protection of hepatocytes by gut-derived hepatocyte growth factor.

Objective Clinical and experimental studies suggest that impairment of the mucosal barrier system increases gut-derived endotoxin in the portal blood, which causes liver injury. The aim of this study was to elucidate the mechanism of liver injury caused by gut defence failure. Design Wistar rats were administered either enteral lipopolysaccharide (LPS) or LPS via the portal vein. Methods Blood samples were collected via the inferior vena cava at necropsy. Serum aspartate transaminase (AST) and alanine transaminase (ALT) were analysed by standard enzymatic procedures and cytokines [tumour necrosis factor-α, interleukin (IL)-1β, interferon-γ, IL-6 and hepatocyte growth factor (HGF)] were measured by enzyme-linked immunosorbent assay. Livers were removed and snap-frozen in liquid nitrogen. CD14, CD68, Toll-like receptor (TLR) 2, TLR4 and Fas ligand (FasL) were analysed immunohistochemically. Expression of TLR2, TLR4 and CD14 mRNA was determined by reverse transcriptase-polymerase chain reaction. Results In enterally-treated rats, AST and ALT were not increased and cytokine levels were under the limits of detection in the absence of a rise in HGF. Enteral administration of LPS increased HGF dose-dependently. Injection of LPS in the portal vein resulted in significant increases in AST, ALT, tumour necrosis factor-α, IL-1β, interferon-γ and IL-6 levels, but no change in HGF levels. Immunohistochemical analysis revealed that intraportal LPS administration increased CD14, TLR4, CD68 and FasL. Reverse transcriptase-polymerase chain reaction analysis demonstrated that TLR4 mRNA expression was upregulated 0.5 h after intraportal LPS administration. Conclusion s Our data suggest that Kupffer cell activation mediated by intraportal LPS via TLR4 is involved in liver injury, possibly through both tumour necrosis factor-α/IL-1β and FasL, and that lack of HGF activity in the impaired gut could not counteract liver injury.

A Case of Resected Cholangiolocellular Carcinomaduring Treatment for Lung Cancer

A Case of Resected Cholangiolocellular Carcinoma during Treatment for Lung Cancer Cholangiolocellular carcinoma is an extremely rare malignant primary liver tumor, accounting for less than 1% of primary liver tumors. We herein report a case of cholangiolocellular carcinoma during treatment for lung cancer. A woman following up after operation for lung cancer was found to have a solitary hepatic tumor in the left lobe of the liver at an abdominal computed tomography checkup. It showed early enhancement with hypovascular area of the center in the arterial phase and enhancement contrast retention in the delayed phase. The tumor was seen as a hypointense nodule in the hepatocellular phase of EOB magnetic resonance imaging. We diagnosed liver metastasis of lung cancer with differential diagnosis of cholangiocellular carcinoma. We performed extended left lobectomy of the liver. Histological and immunohistochemistry findings were compatible with cholangiolocellular carcinoma./p>