Norihiro Kokudo

History and Basic Technique of Fluorescence Imaging for Hepatobiliary-Pancreatic Surgery

Recently, fluorescence imaging using indocyanine green (ICG) has been used clinically to visualize the vascular/lymphatic anatomy and cancerous tissues in real time during surgery. Potentially, among the best indications for ICG fluorescence imaging are hepatobiliary and pancreatic diseases since not only the fluorescent property of ICG but also its biliary excretion property can be utilized for imaging. In fact, ICG fluorescence imaging is already being used in clinical settings to identify the anatomy of the bile duct during laparoscopic surgery as well as open surgery in cases of liver cancer. 5-aminolevulinic acid is another fluorescent probe that has been administered to humans for identification of malignant glioma, bladder cancer and epidermal tumor, although its application to hepatobiliary and pancreatic diseases has rarely been evaluated. Preclinically, numerous kinds of novel fluorescent probes are being developed to improve the sensitivity and specificity of ICG fluorescence imaging, making in vivo fluorescence imaging one of the most active research fields in the world.

Applications of Indocyanine Green Fluorescence Imaging to Liver Transplantation

Recently, fluorescence imaging using indocyanine green (ICG) has been applied to hepatobiliary surgery. Herein, the clinical applications of ICG fluorescence imaging in cases of liver transplantation are described. First, concomitant use of fluorescence cholangiography following intrabiliary injection of ICG by conventional radiographic cholangiography is useful for determination of the division point of the hepatic duct during donor surgery. Secondly, fluorescence angiography can be used to evaluate the hepatic blood flow after venous reconstruction in recipient surgery. Lastly, ICG fluorescence imaging enables simple and easy evaluation of the portal uptake function in hepatic regions with venous occlusion caused by the division of the major hepatic vein tributaries, information about which is helpful for surgeons to determine the operative indication and need for venous reconstruction, not only in liver transplantation, but also in major hepatic resections for malignancy.

Novel Fluorescent Probes for Identification of Liver Cancer and Pancreatic Leak

Although fluorescence imaging using indocyanine green enables highly sensitive intraoperative visualization of liver cancer through allowing visualization of disordered biliary excretion in differentiated hepatocellular carcinoma tissues and in noncancerous liver parenchyma around metastatic liver cancers, we need compensatory imaging techniques for identification of adenocarcinoma tissues during hepatobiliary and pancreatic surgery. Among numerous novel fluorescent probes, γ-glutamyl hydroxymethyl rhodamine green may have the potential to play this role through rapid enzymatic reaction between the probe and γ-glutamyltranspeptidase, which is often overexpressed on the cell membrane of cancer cells. This kind of fluorescent probe based on enzymatic reactions may also be used to detect pancreatic leaks during digestive surgery and to predict the risk of development of postoperative symptomatic pancreatic fistula, which is absolutely essential to further enhance the safety of pancreatic surgery.

Chapter 93A – Preoperative portal vein embolization: Rationale, indications, and results

Currently, hepatic resection is considered to be the only curative treatment for large and/or multiple hepatocellular carcinomas (HCCs) because liver transplantation or ablative therapy is not indicated for most of these tumors. In patients with large and/or multiple HCCs, major hepatic resection (the resection of three or more Couinaud segments)1 is often required to achieve good results. Moreover, since HCC frequently metastasizes via the portal venous system, anatomic hepatic resections including right or left hemihepatectomy provide better longterm results.2–5 Although recent advances in hepatobiliary surgical techniques have improved both the shortand long-term outcomes after hepatic resection for liver tumors, coexisting impaired hepatic functional reserve is still a major cause of operative morbidity after extensive hepatic resection. Because most patients with HCC have impaired hepatic functional reserves due to hepatitis B or C virus–associated liver cirrhosis, the

Liver Biopsy in Transplantation: Nonalcoholic Fatty Liver Disease and the Eosinophils

Liver biopsy is important in the perioperative management of liver transplantation with regard to the preoperative evaluation of donor liver graft, especially to rule out steatotic liver, and the postoperative diagnosis of acute cellular rejection (ACR), especially to differentiate ACR from other causes of liver dysfunction. In both situations, liver biopsy is mandatory to confirm the diagnosis. The recent increases in metabolic syndrome and diabetes mellitus in the general population have led to an increased incidence of liver steatosis, even in donors without a history of excessive alcohol intake. Nonalcoholic fatty liver disease (NAFLD) includes a broad spectrum of liver injuries that resemble alcoholic hepatitis, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). NASH is the progressed stage of NAFLD and further progression results in fibrosis and cirrhosis, which might also be an indication for liver transplantation. ACR is one of the most serious adverse events after transplantation. It is often difficult to distinguish it from recurrent hepatitis C virus (HCV), and prompt treatment with an appropriate diagnosis is important. In this chapter, the indications for liver biopsy and the histologic findings for the diagnosis of NAFLD and ACR are described.