Successful curative resection of gallbladder cancer following S-1 chemotherapy: A case report and review of the literature

Abstract

The symptoms of gallbladder cancer (GBC) are vague and non-specific. Therefore, GBC is often detected at an advanced or metastatic stage. The most effective treatment for GBC is surgical resection, however the majority of GBC cases are unresectable at the time of diagnosis. Therefore, numerous GBC patients undergo chemotherapy. This study reports the case of a 60-year-old female with GBC who underwent successful surgical curative resection following a single dose of the chemotherapeutic agent, S-1, twice daily for 4 weeks followed by a 14-day rest period for 36 months. S-1 is a novel orally administered drug composed of a combination of the 5-fluorouracil (5-FU) prodrug, tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and oteracil potassium in a 1:0.4:1 molar concentration ratio. The focus of the present study was the candidate factors that affect the therapeutic efficacy of S-1-based chemotherapy. In particular, the gene expression involved in the S-1 metabolic pathway was investigated by assessing the intratumoral dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS) and orotate phosphoribosyltransferase gene expression. The surgical specimen exhibited high intratumoral DPD gene expression levels compared with those observed in previously reported non S-1 responsive cases of biliary tract cancer. Due to the results obtained in the current study, we hypothesize that CDHP enhanced the antitumor efficacy of 5-FU by inhibiting the excess DPD protein produced by the tumor.

Keywords: S-1; gallbladder cancer; gene expression.

Figure 1

Computed tomography scans revealing (A) direct invasion of the right hepatic artery and (B) perineural invasion of the common hepatic and celiac arteries.

Figure 2

Changes in the patient CEA and CA19-9 levels (A) prior to chemotherapy and (B)six and (C) 27 months following chemotherapy, and computed tomography findings. (D) Clinical course of S-1 treatment. CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; TS-1, thymidylate synthase; PTPE, percutaneous transhepatic portal embolization.

Figure 3

Changes after chemotherapy (A) in the gallbladder tumor and (B) in terms of neural invasion, shown by computed tomography imaging. (A) A clear reduction in size and decreased invasion was observed in the right hepatic artery. (B) Decreased perineural invasion of the common hepatic and celiac arteries was observed.

Figure 4

Pathological examination demonstrated that the tumor was (A) a scirrhous adenocarcinoma and (B) predominantly consisted of fibrosis and necrosis tissue [stain, hematoxylin and eosin; magnification (A) ×200 and (B) ×40.