Adjuvant Chemotherapy in Resectable Cholangiocarcinoma Patients

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

Disclosures

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

In This Article

Abstract and Introduction

Abstract

Background and Aim Cholangiocarcinoma patients usually have poor treatment outcome and a high mortality rate. The role of adjuvant chemotherapy (AC) is controversial. Our study aimed to evaluate benefits of AC in resectable cholangiocarcinoma patients.

Methods A retrospective study included 263 patients who underwent curative resection in Srinakarind University Hospital. These patients had pathological reports showing a clear margin (R0) or microscopic margin (R1) of lesion-free tissue.

Results There were 138 patients who received AC. This group had a significantly lower mean age than patients not receiving adjuvant chemotherapy (NAC) group (57.7 ± 8.5 vs 60.4 ± 9.0 years, P = 0.01). The level of serum albumin above 3 g/dL was more common in AC group than the NAC one (87.7% vs 79.2%, P = 0.04). Patients who received AC had significantly longer overall median survival time (21.6 vs 13.4 months, P = 0.01). Patients with a combination of gemcitabine and capecitabine regimen had the longest survival time (median overall survival time of gemcitabine and capecitabine 31.5, 5-fluorouracil and mitomycin 17.3, 5-fluorouracil alone 22.2, capecitabine alone 21.6, and gemcitabine alone 7.9 months, P = 0.02). Benefits of AC were likely to be found in patients who had high-risk features, that is, high level of carbohydrate antigen 19–9, advanced stage, T4 stage, lymph node involvement, and R1 margin.

Conclusions AC significantly prolongs survival time in resectable cholangiocarcinoma patients, particularly in the high risk group.

Introduction

Cholangiocarcinoma, a malignant tumor of bile duct epithelium, is a common malignancy in Thailand, especially in the northeast and north regions. However, it is a rare malignancy in Europe and America.[1,2] Cholangiocarcinoma is more common in males than females (incidence 135.4 vs 43 per 100 000 populations).[2] Risk factors are primary sclerosing cholangitis, Opisthorchis viverrini infection, Clonorchis sinensis infection, biliary malformation, such as Caroli's disease and congenital fibropolycystic disease. Recently, chronic viral hepatitis B and C infection were also demonstrated as risk factors of cholangiocarcinoma.[3,4] Cholangiocarcinoma is classified into two types by anatomical structure, intrahepatic and extrahepatic types. Extrahepatic cholangiocarcinoma is further categorized into two groups, perihilar and distal types.[5] Perihilar type is the most common type which usually presents with obstructive jaundice, while intrahepatic cholangiocarcinoma patients commonly present with abdominal pain.[6] Cholangiocarcinoma is a disease with a high mortality rate because the first presentation is often in an advanced stage.[5,7] Surgery is a standard treatment for local disease. The overall survival rate of cholangiocarcinoma is low.[8] The surgical margins and lymph node metastases are important factors to determine prognosis in resectable cholangiocarcinoma patients.[6,9] Previous studies reported that 5-year overall survival in resectable cases ranged from 8 to 44%, and was significantly better in patients with a clear surgical margin than with a small or indistinct one.[7]

Adjuvant chemotherapy (AC), a standard treatment in various malignancies, improves disease-free survival and overall survival of patients.[10–13] However, benefits of AC in resectable cholangiocarcinoma patients are controversial.[14] Benefits of AC are difficult to evaluate for several reasons. First, previous studies enrolled a limited number of patients.[15] Second, some studies evaluated cholangiocarcinoma together with gall bladder cancer and ampulla of Vater cancer.[16–18] Thus, our study aimed to determine benefits of AC in resectable cholangiocarcinoma patients.

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