Early hepatocellular carcinoma as a signaling lesion for subsequent malignancy.
OBJECTIVE
Early diagnosis and treatment of cancer may contribute substantially to complete cure, but it remains unknown whether treatment of early hepatocellular carcinoma can actually result in cure. This study was performed to clarify the cancer risk of the background liver after treating early hepatocellular carcinoma.


METHODS
Early hepatocellular carcinoma is defined as very well-differentiated cancer containing Glisson's triad. The cumulative incidence of classical hepatocellular carcinoma, hypervascular liver cancer detected on imaging studies, after resection of early hepatocellular carcinoma positive for anti-hepatitis C antibody (early hepatocellular carcinoma group, n = 105) was compared with that in patients with chronic liver disease positive for anti-hepatitis C antibody (control group, n = 751) and propensity score-matched patients after resection of classical hepatocellular carcinoma (classical hepatocellular carcinoma group, n = 105).


RESULTS
After a median follow-up of 4.8 years (range, 0.3-15.0), the cumulative incidence of classical hepatocellular carcinoma at 5 years was 56.9% (95% confidence interval, 44.2-67.7%) in the early hepatocellular carcinoma group and 70.6% (52.5-81.8%) in the classical hepatocellular carcinoma group as compared with 4.6% (2.8-6.4%) in the control group. The risk of the development of classical hepatocellular carcinoma in the early hepatocellular carcinoma group was significantly higher than that in the control group (hazard ratio, 17.5; 95% confidence interval, 12.1-25.3; P < 0.001) and significantly lower than that in the classical hepatocellular carcinoma group (hazard ratio, 0.60; 0.41-0.89; P = 0.010). However, the cumulative incidence of second primary hepatocellular carcinoma in patients with one early hepatocellular carcinoma did not differ significantly from that in patients with two or more early hepatocellular carcinoma lesions (hazard ratio, 1.50; 0.85-2.65; P = 0.157).


CONCLUSIONS
Treatment of early hepatocellular carcinoma cannot provide complete cure due to the substantial risk of developing classical hepatocellular carcinoma.
Department of Digestive Surgery, Nihon University School of Medicine, Tokyo.
Yutaka
Y
Midorikawa
Department of Digestive Surgery, Nihon University School of Medicine, Tokyo takayama.tadatoshi@nihon-u.ac.jp.
Tadatoshi
T
Takayama
Department of Digestive Surgery, Nihon University School of Medicine, Tokyo.
Tokio
T
Higaki
Department of Digestive Surgery, Nihon University School of Medicine, Tokyo.
Hisashi
H
Nakayama
Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo.
Masakazu
M
Yamamoto
Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo.
Shunichi
S
Ariizumi
Hepato-Biliary-Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo.
Kazuaki
K
Shimada
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, University of Tokyo , Tokyo.
Norihiro
N
Kokudo
Genome Science Division, Research Center for Advanced Science and Technologies, University of Tokyo, Tokyo.
Shingo
S
Tsuji
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Kaoru
K
Tsuchiya
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Masayuki
M
Kurosaki
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Namiki
N
Izumi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D016016:Proportional Hazards Models; D012307:Risk Factors; D015996:Survival Rate
D018937:Hepatitis C Antibodies
early cancer; hypovascular HCC; multicentric hepatocarcinogenesis; preclinical phase; second primary HCC