Masaru Miyazaki

IL-13 Activates STAT6 and Inhibits Liver Injury Induced by Ischemia/Reperfusion

Hepatic ischemia/reperfusion injury is initiated by the activation of Kupffer cells and their subsequent release of proinflammatory mediators, including tumor necrosis factor-alpha (TNFalpha). These mediators stimulate a cascade of events including up-regulation of CXC chemokines and vascular endothelial adhesion molecules, leading to hepatic neutrophil recruitment and tissue injury. Interleukin-13 (IL-13) is a cytokine that has been shown to suppress macrophage production of proinflammatory mediators. The objective of the current study was to determine whether IL-13 could regulate the liver inflammatory injury induced by ischemia and reperfusion. C57BL/6 mice underwent 90 minutes of partial hepatic ischemia followed by reperfusion with or without intravenous administration of recombinant murine IL-13. Hepatic ischemia/reperfusion increased expression of TNFalpha and macrophage inflammatory protein-2 (MIP-2), leading to hepatic neutrophil recruitment, hepatocellular injury, and liver edema. Administration of IL-13 reduced the production of TNFalpha and MIP-2 mRNA and protein. IL-13 suppressed liver neutrophil recruitment by up to 72% and hepatocellular injury and liver edema were each reduced by >60%. Administration of IL-13 had no effect on liver NFkappaB activation, but greatly increased the activation of STAT6. The data suggest that the hepatoprotective effects of IL-13 may be a result of STAT6 activation.

Left-sided Hepatectomy (Left Hemihepatectomy or Left Trisectionectomy) Extending to the Caudate Lobe with Bile Duct Resection for Perihilar Cholangiocarcinoma

Left-sided hepatectomy (left hemihepatectomy or left trisectionectomy) extending to the caudate lobe with bile duct resection has been recognized as a standard treatment option for perihilar cholangiocarcinoma of the left-side predominance. From the viewpoint of anatomical factors at the hepatic hilus, left-sided hepatectomy is considered to be a more complicated procedure, requiring greater skill, than right-sided hepatectomy. As there are many anatomical variations of the sectional artery and bile duct in the right liver (remnant side), preoperatively evaluating individual 3-D hilar anatomy is essential for successful surgery.

Fluorescence Cholangiography in Open Surgery

Although indocyanine green (ICG) fluorescence imaging has long been used in surgery for research purposes, its clinical use began relatively recently and is growing rapidly. ICG fluorescence imaging has advantages in that it: (1) enables the easy, rapid and real-time observation of internal organs using a safe agent, (2) has very high sensitivity, and (3) can identify pathological changes after repeated ICG administration. Therefore, it is widely used in many clinical departments for angiography, lymphangiography, sentinel lymph node visualization and tissue viability detection. The specificity of ICG kinetics makes it possible to acquire diverse information through its time-course distribution into the blood stream, liver parenchyma and biliary tract during abdominal surgery. Indeed, in biliary tract surgery the identification of arteries, veins and bile ducts by taking advantage of the transparency of biological tissues to infrared light, accurate identification of liver segments during intraportal ICG injection, its application in gallbladder cancer surgery based on the identification of the cystic vein perfusion area, utilization of its uptake in hepatocellular carcinoma and metastatic cancer in the liver, and high-sensitivity visualization of bile leakage during hepatectomy have been reported. In addition, ICG imaging has been performed during laparoscopy, making it a very useful technique in abdominal and laparoscopic surgeries. This technology is expected to be further utilized and advanced, and to contribute to clinical practice. This chapter describes the application of ICG fluorescence-based cholangiography to abdominal open surgery.