title: Successful treatment of advanced gallbladder cancer with an anticancer drug S-1: assessment based on intratumoral gene.
abstract: While surgical resection is the most effective treatment for gallbladder cancer, most of these cancers are not resectable at the time of diagnosis, and therefore, chemotherapy serves as the primary therapy in many cases. However, to date, there is no standard chemotherapy for this cancer. We report a case of advanced gallbladder cancer for which the anticancer drug S-1 was effective. The patient was a 53-year-old woman who presented with a huge ovarian tumor. On workup, all abdominal images revealed the presence of advanced gallbladder cancer that had invaded the liver. Because the gallbladder formed a relatively hard and swollen mass involving the omentum, as revealed during exploration, the surgical resection of the gallbladder was not possible at that time, and only hysterectomy and bilateral salpingo-oophorectomy were performed. She started on the anticancer drug S-1 just after this operation. S-1 is a prodrug of 5-fluorouracil (5-FU), and contains 5-chloro-2-4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase (DPD) that rapidly degrades 5-FU. Eight months after the first operation, radical cholecystectomy was performed. Pathologically, the tumor was diagnosed as an adenocarcinoma of the gallbladder, and no evidence of liver invasion was found. Intratumoral gene expression analysis of the resected gallbladder revealed significantly elevated DPD expression. We suggest that the rapid degradation of 5-FU mediated by this high DPD in our patient was significantly blocked by the CDHP in S-1, and that the efficacy of 5-FU was consequently maintained at the maximum level.
authors.affiliation: Department of Surgery, Jikei University School of Medicine, Minato-ku, Tokyo, 105-8461, Japan. Kmkktjm@aol.com
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kitajima
authors.forename: Susumu
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiba
authors.forename: Tadashi
authors.initials: T
authors.lastname: Uwagawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishida
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aiba
authors.forename: Makio
authors.initials: M
authors.lastname: Kawakami
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanaga
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics* / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000378:metabolism; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D006801:Humans; D008875:Middle Aged; D010094:Oxonic Acid / Q000627:therapeutic use*; D005641:Tegafur / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil