Adjuvant Chemotherapy in Resectable Cholangiocarcinoma Patients

Kosin Wirasorn; Thundon Ngamprasertchai; Narong Khuntikeo; Ake Pakkhem; Piti Ungarereevittaya; Jarin Chindaprasirt; Aumkhae Sookprasert


J Gastroenterol Hepatol. 2013;28(12):1885-1891. 

In This Article

Materials and Methods


A retrospective study was conducted among newly diagnosed cholangiocarcinoma cancer patients, who underwent curative resection in Srinakarind Hospital, Khon Kaen University (a 1000-bed university hospital), Khon Kaen, Thailand, during January 2009–December 2011. Curative resection was defined as a total excision of the entire tumor, including the primary tumor and the associated lymph node drainage fields. These patients had pathological reports with clear margins (R0) or microscopic margins (R1). All patients were classified into two groups: the AC group included patients who received postoperative chemotherapy and a control group. Demographic data included sex, age, underlying diseases including diabetes mellitus, body weight, height, first clinical symptoms, and hepatomegaly. Body mass index (BMI) was calculated from weight in kilograms divided by the square of the height in meters (kg/m2). BMI cutoffs were classified according to the World Health Organization criteria for Asian and Pacific populations (underweight, < 18.5; healthy, 18.5–22.9; at risk, 23–24.9; obese I, 25–29.9; and obese II, ≥ 30 kg/m2). Preoperative liver function status including total bilirubin, cholesterol, alanine transaminase, aspartate aminotransferase, and alkaline phosphatase, as well as serum tumor markers including carbohydrate antigen (CA19–9) and carcinoembryonic antigen were evaluated. Tumor staging, local disease or metastasis, were determined by appropriate investigations, that is, ultrasonography, computed tomography, magnetic resonance imaging, magnetic resonance cholangiopancreatography, and endoscopic retrograde pancreatocholangiography. Preoperative percutaneous transhepatic biliary drainage was performed in patients with jaundice. Some patients received preoperative percutaneous transhepatic portal embolization of the resected liver segment to induce compensatory hypertrophy of the future remnant liver. Major hepatectomy was performed for patients with intrahepatic cholangiocarcinoma and proximal type of extrahepatic cholangiocarcinoma, while surgical procedures for patients with distal cholangiocarcinoma were subjected to pancreaticoduodenectomy. Regional lymph nodes in the hepatoduodenal ligament, pancreaticoduodenal nodes, and along the common hepatic artery were evaluated in all patients. Furthermore, lymph nodes along the superior mesenteric artery were also explored in patients who underwent pancreaticoduodenectomy.

All specimens were examined by a qualified pathologist. Location of the primary tumor, tumor grading, type of histology, tumor invasion, and surgical margins in each patient were reported. The final stage of bile duct tumor was determined according to the TNM classification system of malignant tumors published by American Joint Committee on Cancer (AJCC), 7th edition. AC was administered in patients who had good performance status and adequate bone marrow reserves (absolute neutrophil count more than 1500/mm3, platelet count more than 100 000/mm3, and hemoglobin level more than 8 g/dL), adequate renal function (glomerular function rate determined by Cockcroft-Gault equation more than 60 mL/min), and adequate excretory function of liver (total serum bilirubin less than 3 mg/dL). Regimens of chemotherapy in our institution were single agent chemotherapy including gemcitabine, 5-fluorouracil (5-FU), and capecitabine, and combination chemotherapy regimens including gemcitabine combining with capecitabine and 5-FU combining with mitomycin C.

Statistical Analysis

The primary end point was to determine median overall survival time and survival rate in the AC patients compared with the control group. The survival time was defined as date of diagnosis to date of death from any cause or last follow up. Patients' characteristics and tumor data were summarized as mean and percentage. Comparison of the patients' characteristic and tumor data between the AC patients group and NAC group were performed by the Chi-square test. Differences in survival time were presented by the Kaplan–Meier curve between the AC and the NAC groups. Each variable factor was subcategorized for additional analysis to evaluate benefits of AC in each subgroup. The statistical analyses were performed by using SPSS software version 20.0 (SPSS, Inc., Chicago, IL, USA). A P value ≤ 0.05 was considered statistically significant. The study was reviewed and approved by the institutional review board (HE 551183). The database was closed for analysis in August 2012.