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Outcome of Combined Hepatocellular and Cholangiocarcinoma of the Liver

DOI: 10.1155/2010/917356

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Background. The objective of this study was to examine the epidemiology, natural history, and prognostic factors of combined hepatocellular and cholangiocarcinoma (cHCC-CC) using population-based registry. Methods. The Surveillance, Epidemiology, and End Results Program database (1973–2004) was used to identify cases of cHCC-CC. Multivariable logistic regression was used to evaluate factors associated with cancer-directed surgery (CDS). The influence of CDS on cancer specific survival was evaluated using Kaplan-Meier curves and Cox proportional hazards modeling. Results. A total of 380 cases of cHCC-CC were identified, which account for approximately 0.87% of primary liver tumors. Of all patients, 69.8% of patients had regional or distant stage; 65.6% of patients had poorly or undifferentiated histology. Only 44.9% of patients with localized disease, received CDS. By logistic regression analysis, being widowed, advanced stage, and earlier diagnosis year were associated with lower rate of utilization of CDS. In multivariate analysis, tumor stage, receipt of CDS, and recent year of diagnosis were found to be significant predictors for cancer-specific survival. Conclusions. Patients with localized cHCC-CC who are selected for CDS were strongly associated with improved survival. However, many patients with localized tumors did not receive potentially curative cancer-directed surgery. Further study is warranted to address the barriers to the delivery of appropriate care to these patients. 1. Introduction Combined hepatocellular and cholangiocarcinoma (cHCC-CC) is an uncommon subtype of primary liver cancer [1, 2]. The disease was first described in 1949 by Allen and Lisa and has been defined as the intimate intermingling of both a HCC component and CC component Two histopathological classification schemes have been proposed Allen and Lisa [1] described three groups, type A with HCC and CC present at different sites within the same liver, and type B with HCC and CC present at adjacent sites and mingle with continued growth, and type C with HCC and CC are combined in the same tumor. Goodman et al. [2] categorized cHCC-CC into three types: collision type, transitional type, and fibrolamellar type. Kim et al. [3] and Zhang et al. [4] proposed that cHCC-CC is a distinct type of primary liver carcinoma, which is morphologically and phenotypically intermediate between HCC and CC and may be derived from hepatic progenitor cells with the bipotential to differentiate into both hepatocytic and cholangiocytic lineages. Because of the rarity of cHCC-CC, previously


[1]  R. Allen and J. A. Lisa, “Combined liver cell and bile duct carcinoma,” American Journal of Pathology, vol. 25, pp. 647–655, 1949.
[2]  Z. D. Goodman, K. G. Ishak, and J. M. Langloss, “Combined hepatocellular cholangiocarcinoma. A histologic and immunohistochemical study,” Cancer, vol. 55, no. 1, pp. 124–135, 1985.
[3]  H. Kim, C. Park, K.-H. Han, J. Choi, Y. B. Kim, J. K. Kim, and Y. N. Park, “Primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype,” Journal of Hepatology, vol. 40, no. 2, pp. 298–304, 2004.
[4]  F. Zhang, X.-P. Chen, W. Zhang, H.-H. Dong, S. Xiang, W.-G. Zhang, and B.-X. Zhang, “Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence,” Histopathology, vol. 52, no. 2, pp. 224–232, 2008.
[5]  J. Taguchi, O. Nakashima, M. Tanaka, T. Hisaka, T. Takazawa, and M. Kojiro, “A Clinicopathological study on combined hepatocellular and cholangiocarcinoma,” Journal of Gastroenterology and Hepatology, vol. 11, no. 8, pp. 758–764, 1996.
[6]  T. Maeda, E. Adachi, K. Kajiyama, K. Sugimachi, and M. Tsuneyoshi, “Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features,” Human Pathology, vol. 26, no. 9, pp. 956–964, 1995.
[7]  Y. Imai, H. Oda, M. Arai, S. Shimizu, Y. Nakatsuru, T. Inoue, and T. Ishikawa, “Mutational analysis of the p53 and K-ras genes and allelotype study of the Rb-1 gene for investigating the pathogenesis of combined hepatocellular-cholangiocellular carcinomas,” Japanese Journal of Cancer Research, vol. 87, no. 10, pp. 1056–1062, 1996.
[8]  T. Wakasa, K. Wakasa, and K. Wakasa, “A histopathological study on combined hepatocellular and cholangiocarcinoma: cholangiocarcinoma component is originated from hepatocellular carcinoma,” Hepatogastroenterology, vol. 54, no. 74, pp. 508–513, 2007.
[9]  H.-Q. Zuo, L.-N. Yan, Y. Zeng, J.-Y. Yang, H.-Z. Luo, J.-W. Liu, and L.-X. Zhou, “Clinicopathological characteristics of 15 patients with combined hepatocellular carcinoma and cholangiocarcinoma,” Hepatobiliary and Pancreatic Diseases International, vol. 6, no. 2, pp. 161–165, 2007.
[10]  S. Chantajitr, C. Wilasrusmee, P. Lertsitichai, and N. Phromsopha, “Combined hepatocellular and cholangiocarcinoma: clinical features and prognostic study in a Thai population,” Journal of Hepato-Biliary-Pancreatic Surgery, vol. 13, no. 6, pp. 537–542, 2006.
[11]  W.-S. Lee, K.-W. Lee, J.-S. Heo, S.-J. Kim, S.-H. Choi, Y.-I. Kim, and J.-W. Joh, “Comparison of combined hepatocellular and cholangiocarcinoma with hepatocellular carcinoma and intrahepatic cholangiocarcinoma,” Surgery Today, vol. 36, no. 10, pp. 892–897, 2006.
[12]  J. Taguchi, O. Nakashima, M. Tanaka, T. Hisaka, T. Takazawa, and M. Kojiro, “A Clinicopathological study on combined hepatocellular and cholangiocarcinoma,” Journal of Gastroenterology and Hepatology, vol. 11, no. 8, pp. 758–764, 1996.
[13]  I. O. L. Ng, T. W. H. Shek, J. Nicholls, and L. T. Ma, “Combined hepatocellular-cholangiocarcinoma: a clinicopathological study,” Journal of Gastroenterology and Hepatology, vol. 13, no. 1, pp. 34–40, 1998.
[14]  R. T. Poon, S. T. Fan, and S. T. Fan, “Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database,” Annals of Surgery, vol. 240, no. 4, pp. 698–708, 2004.
[15]  W. R. Jarnagin, S. Weber, and S. Weber, “Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors,” Cancer, vol. 94, no. 7, pp. 2040–2046, 2002.
[16]  K. C. Koh, H. Lee, and H. Lee, “Clinicopathologic features and prognosis of combined hepatocellular cholangiocarcinoma,” American Journal of Surgery, vol. 189, no. 1, pp. 120–125, 2005.
[17]  T. Uenishi, K. Hirohashi, and K. Hirohashi, “Surgically treated cases of mixed hepatocellular carcinoma and cholangiocarcinoma,” Hepatogastroenterology, vol. 49, no. 46, pp. 1083–1086, 2002.
[18]  C.-L. Liu, S.-T. Fan, C.-M. Lo, I. O.-L. Ng, C.-M. Lam, R. T.-P. Poon, and J. Wong, “Hepatic resection for combined hepatocellular and cholangiocarcinoma,” Archives of Surgery, vol. 138, no. 1, pp. 86–90, 2003.
[19]  L. McCormack, H. Petrowsky, and P.-A. Clavien, “Surgical therapy of hepatocellular carcinoma,” European Journal of Gastroenterology and Hepatology, vol. 17, no. 5, pp. 497–503, 2005.
[20]  Surveillance, Epidemiology, and End Results (SEER) Program, Public-Use Data (1973–2004), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, April 2002,
[21]  “SEER Summary Staging Manual,” 2000,
[22]  Y. Shiratori, H. Yoshida, and M. Omata, “Management of hepatocellular carcinoma: advances in diagnosis, treatment and prevention,” Expert Review of Anticancer Therapy, vol. 1, no. 2, pp. 277–290, 2001.
[23]  C. J. Sonnenday, J. B. Dimick, R. D. Schulick, and M. A. Choti, “Racial and geographic disparities in the utilization of surgical therapy for hepatocellular carcinoma,” Journal of Gastrointestinal Surgery, vol. 11, no. 12, pp. 1636–1646, 2007.
[24]  D. Sloane, H. Chen, and C. Howell, “Racial disparity in primary hepatocellular carcinoma: tumor stage at presentation, surgical treatment and survival,” Journal of the National Medical Association, vol. 98, no. 12, pp. 1934–1939, 2006.
[25]  Y. Fukukura, J. Taguchi, O. Nakashima, Y. Wada, and M. Kojiro, “Combined hepatocellular and cholangiocarcinoma: correlation between CT findings and clinicopathological features,” Journal of Computer Assisted Tomography, vol. 21, no. 1, pp. 52–58, 1997.
[26]  S. Phongkitkarun, T. Srisuwan, P. Sornmayura, and J. Jatchavala, “Combined hepatocellular and cholangiocarcinoma: CT Findings with emphasis on multiphasic helical CT,” Journal of the Medical Association of Thailand, vol. 90, no. 1, pp. 113–120, 2007.
[27]  J. Bruix, A. J. Hessheimer, A. Forner, L. Boix, R. Vilana, and J. M. Llovet, “New aspects of diagnosis and therapy of hepatocellular carcinoma,” Oncogene, vol. 25, no. 27, pp. 3848–3856, 2006.
[28]  S.-T. Fan, C.-M. Lo, C.-L. Liu, C.-M. Lam, W.-K. Yuen, C. Yeung, and J. Wong, “Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths,” Annals of Surgery, vol. 229, no. 3, pp. 322–330, 1999.
[29]  S. Virani, J. S. Michaelson, and J. S. Michaelson, “Morbidity and mortality after liver resection: results of the patient safety in surgery study,” Journal of the American College of Surgeons, vol. 204, no. 6, pp. 1284–1292, 2007.
[30]  V. Mazzaferro, E. Regalia, and E. Regalia, “Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis,” New England Journal of Medicine, vol. 334, no. 11, pp. 693–699, 1996.
[31]  C. G. Meyer, I. Penn, and L. James, “Liver transplantation for cholangiocarcinoma: results in 207 patients,” Transplantation, vol. 69, no. 8, pp. 1633–1637, 2000.
[32]  A. C.-Y. Chan, C. M. Lo, I. O.-L. Ng, and S. T. Fan, “Liver transplantation for combined hepatocellular cholangiocarcinoma,” Asian Journal of Surgery, vol. 30, no. 2, pp. 143–146, 2007.
[33]  J. M. Llovet, M. I. Real, X. Montana, et al., “Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial,” The Lancet, vol. 359, no. 9319, pp. 1734–1739, 2002.
[34]  S. Okada, “Local ablation therapy for hepatocellular carcinoma,” Seminars in Liver Disease, vol. 19, no. 3, pp. 323–328, 1999.
[35]  E. A. Dick, S. D. Taylor-Robinson, H. C. Thomas, and W. M. W. Gedroyc, “Ablative therapy for liver tumours,” Gut, vol. 50, no. 5, pp. 733–739, 2002.
[36]  W. T. Kassahun and J. Hauss, “Management of combined hepatocellular and cholangiocarcinoma,” International Journal of Clinical Practice, vol. 62, no. 8, pp. 1271–1278, 2008.


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