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.
Highlights
Gallbladder cancer (GBC) is the most aggressive type of biliary tract cancer (BTC) and exhibits the shortest median survival time worldwide
The most effective treatment for GBC is surgical resection; the majority of GBCs are unresectable at the time of diagnosis [1,12,13] and, numerous GBC patients undergo chemotherapy [14]
Primary systemic chemotherapy appears to be a promising approach to the management of patients with initially unresectable liver metastases, as it leads to a reduction in the lesion size, which facilitates the surgical resection in a high proportion of cases [15]
Summary
Gallbladder cancer (GBC) is the most aggressive type of biliary tract cancer (BTC) and exhibits the shortest median survival time worldwide. The current study presents a case of GBC in which the patient underwent successful surgical curative resection following a single dose of S‐1. An abdominal computed tomography (CT) scan revealed the presence of advanced GBC, which had invaded the liver, as well as regional lymph node metastasis and perineural invasion of the common hepatic and celiac arteries (Fig. 1). The tumor marker levels decreased after two months(Fig. 2), and a CT scan demonstrated a clear reduction in size in the regions of the liver that were invaded by the GBC, as well as those affected by lymph node metastasis and perineural invasion (Fig. 3). The resected gallbladder specimen was analyzed to determine the intratumoral gene expression levels of DPD, OPRT and TS, which encode the corresponding key enzymes that are involved in the metabolism of 5‐FU [8,9]. The specimen exhibited high intratumoral DPD gene expression levels compared with those observed in the BTC cases who were non-responders of S-1 treatment (Table I)
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