title: Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma. Updated analysis of the long-term follow-up data.
abstract: Oral administration with acyclic retinoid, a synthetic vitamin A analog, for a limited period of 12 months (48 weeks) prevented the development of second primary hepatocellular carcinoma (HCC) and also improved the survival of patients who underwent curative treatments of the initial tumor. Following that randomized controlled study reported in 1996 and 1999, we have continued to follow up the patients by medical imaging and blood chemical analyses, and found that the preventive effect of acyclic retinoid lasted up to 199 weeks after randomization (or 151 weeks after completion of retinoid administration). The retinoid's effect was not mediated by reduction in hepatic necro-inflammation since no significant decrease in serum aminotransferase activity was seen in the retinoid group. Such observation seems quite distinct from the cancer-preventive mechanism of interferon, a potent immunopreventive agent for HCC. We have also shown here the reduction by the retinoid in serum levels of lectin-reactive alpha-fetoprotein (AFP-L3) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), both of which indicate the presence of latent HCC cells. These results suggest that acyclic retinoid may delete such malignant clones before they expand to clinically detectable tumors and thereby inhibited second primary HCC. Once such latent clones are eradicated, it may well take at least several years for the next cancer clone to arise clinically. This may possibly explain a reason for the long-term effect of the retinoid even after the limited period of administration.
authors.affiliation: Department of Gastroenterology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Takai
authors.forename: Masataka
authors.initials: M
authors.lastname: Okuno
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yasuda
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Uematsu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tsurumi
authors.forename: Yoshimune
authors.initials: Y
authors.lastname: Shiratori
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Muto
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000517:prevention & control*; D006801:Humans; D007564:Japan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D016609:Neoplasms, Second Primary / Q000517:prevention & control*; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D016019:Survival Analysis; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D014212:Tretinoin; C034534:3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid; D011516:Prothrombin; D001219:Aspartate Aminotransferases