Management of Hepatocellular Carcinoma in Japan as a World-Leading Model

Japan has achieved highly favorable outcomes in hepatocellular carcinoma (HCC) treatment. Several factors contributed to this achievement as shown in Tables ​Tables11 and ​and2.2. The establishment of a nationwide liver cancer screening program, which was developed in the 1980s and involves institutes across all over Japan, is one of such factors. For example, Japan was the first country in the world to develop and implement diagnostic ultrasound systems for liver cancer screening. In addition to the already established tumor marker α-fetoprotein (AFP), other markers such as protein induced by vitamin K absence or antagonist-II (PIVKA-II) and Lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3) were developed in Japan. These two tumor markers were included among health insurance-covered screening tests in 1989 and 1994, respectively. Japan is the only country in the world in which these three tumor markers are included in routine surveillance under national health insurance without restrictions. Other important achievements in Japan include the invention of transcatheter arterial chemoembolization (TACE) [1], the development and the world's first commercialization of technetium-99m galactosyl human serum albumin liver scintigraphy for the assessment of hepatic functional reserve [2,3], the world's first hepatectomy [4], the development of anatomic liver resection [5], and the invention of local ablation (percutaneous ethanol injection) [6] and percutaneous microwave coagulation therapy [7]. Japan also has the highest number of cases treated with radiofrequency ablation (RFA). Other methods developed in Japan include contrast-enhanced liver ultrasound (initially by intra-arterial infusion of carbon dioxide microbubbles) [8,9]; fusion imaging; perfluorobutane (Sonazoid), a unique ultrasound contrast agent that enables Kupffer-phase imaging; and defect reperfusion imaging using Sonazoid, which assists in screening, definitive diagnosis, and local ablation therapy [10]. Table 1 Epoch-making developments, which were established in Japan first in the world