Surgical treatment of patients with mixed hepatocellular carcinoma and cholangiocarcinoma (1997)

We read with interest the article by Nakamura et al. about the clinical characteristics and surgical results of six cases of mixed hepatocellular carcinoma and cholangiocarcinoma (MHC).1 The authors concluded that a hypervascular tumor with high carcinoembryonic antigen and CA 19-9 levels or a hypovascular tumor with a high α-fetoprotein (AFP) level may suggest a preoperative diagnosis of MHC in patients with suspected HCC, and that extensive surgery is an effective treatment except for patients with satellite nodules. They also concluded that a hilar lymphadenectomy may not be necessary for selected patients. We previously reported 36 cases of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) containing MHC cases, and we proposed the criteria according to cytokeratin expression and clarified the clinicopathologic features of cHCC-CC while also comparing these cases to ordinary hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC).2 Nakamura et al. defined MHC as an intimate intermingling of hepatocellular and glandular elements according to the classification of Allen and Lisa.3 However, the definition and exact criteria for the histologic diagnosis of cHCC-CC have yet to be well defined. Moreover, it is difficult to determine whether a case is a combined type or a mixed type because both components are intimately intermingled and are also partially transformed even in combined-type cases. The diagnosis of cHCC-CC should therefore be made only after a detailed histopathologic examination in which the cytokeratin expression is determined.2, 4 Clinically, our study revealed that the clinical features of cHCC-CC, such as the average patient age, the male-to-female ratio, the hepatitis B surface antigen and hepatitis C virus antibody positivity, the serum AFP level, and the presence of cirrhosis, more closely resembled the features of HCC than those of CC. Nakamura et al. demonstrated that the 5-year survival rate of 6 patients with MHC was 60%, with 2 patients surviving for more than 10 years. The survival rate of patients with MHC in their series thus seems to be substantially better than that of patients with ordinary HCC. In our study, the survival rate after hepatic resection of the 27 patients with cHCC-CC (5-year survival rate, approximately 20%) was significantly lower than that of the 319 patients with HCC, but was identical to that of the 25 patients with CC. Moreover, 9 (31%) of 29 cases of cHCC-CC died within 6 months after hepatic resection. cHCC-CC also metastasized more widely to various organs and lymph nodes. The metastatic lesions were not only composed of CC, but also consisted of both HCC and CC or only HCC. We therefore believe that the high malignant potential of cHCC-CC depends on both the HCC and CC components, rather than only the CC components. We believe that cHCC-CC should therefore be clinically treated as CC, because with regard to its clinical background it is more similar to HCC than to CC, but it has more aggressive biologic behavior than HCC. A dissection of the lymph nodes is also considered to be essential; moreover, postoperative chemotherapy may be needed. In any event, if the histologic diagnosis of MHC cannot be clearly confirmed, the clinical features and prognosis of MHC should not be discussed. Takashi Maeda M.D. Ph.D.*, Masazumi Tsuneyoshi M.D. Ph.D.*, Kenji Takenaka M.D. Ph.D. , Keizo Sugimachi M.D. Ph.D. F.A.C.S.