Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? Yasser H. Shaib 1,2,3 , Jessica A. Davila 1,3 , Kathryn McGlynn 4 , Hashem B. El-Serag 1,2,3, * 1 Section of Health Services Research, The Houston Veterans Affairs Medical Center, Houston, TX, USA 2 Section of Gastroenterology, The Houston Veterans Affairs Medical Center, Houston, TX, USA 3 Baylor College of Medicine, Houston, TX, USA 4 The National Cancer Institute, NIH, Bethesda, MD, USA Background/Aims: The incidence of intrahepatic cholangiocarcinoma (ICC) has been reported to be increasing in the USA. The aim of this study is to examine whether this is a true increase or a reflection of improved detection or reclassification. Methods: Using data from the Surveillance Epidemiology and End Results (SEER) program, incidence rates for ICC between 1975 and 1999 were calculated. We also calculated the proportions of cases with each tumor stage, microscopically confirmed cases, and the survival rates. Results: A total of 2864 patients with ICC were identified. The incidence of ICC increased by 165% during the study period. Most of this increase occurred after 1985. There were no significant changes in the proportion of patients with unstaged cancer, localized cancer, microscopic confirmation, or with tumor size < 5 cm during the period of the most significant increase. The 1-year survival rate increased significantly from 15.8% in 1975 – 1979 to 26.3% in 1995 – 1999, while 5-year survival rate remained essentially the same (2.6 vs. 3.5%). Conclusions: The incidence of ICC continues to rise in the USA. The stable proportions over time of patients with early stage disease, unstaged disease, tumor size < 5 cm, and microscopic confirmation suggest a true increase of ICC. q 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Keywords: Intrahepatic cholangiocarcinoma; SEER; Incidence 1. Introduction The incidence and mortality of intrahepatic cholangio- carcinoma (ICC) has been reported to be increasing worldwide [1–3]. Data from the WHO database indicate a global increase in ICC related mortality [1,2] in countries in Asia, Europe, America and Australia. For example, an increase in ICC-related mortality has been noted in England and Wales [3], and increasing incidence of ICC was also reported in Crete and Japan [4,5]. In the USA, approximately 17 300 new cases of primary liver cancer are diagnosed every year [6]. Data from the NCI’s Surveillance, Epidemiology and End Results (SEER) indicate that approximately 10% of these are cases of ICC, and the rest are hepatocellular carcinoma. Using data from nine SEER registries, Patel reported an increase in the age-adjusted incidence of ICC in the USA from 0.13 per 100 000 in 1973 to 0.67 per 100 000 in 1997 [7]. However, it remains unclear whether this was a true increase or a reflection of increased detection and diagnosis of ICC. Increased detection of cancer is usually associated with an increase in the proportion of patients with early stage cancers, small-size tumors and possibly improved short- term survival. Another possibility is that the increase in ICC incidence is a reflection of increased use of improved diagnostic tests (e.g. ERCP) leading to increased detection or reclassification of hepatobiliary tumors from what would have been previously described as unclassified, extra- hepatic cholangiocarcinoma, or hepatocellular carcinoma. However, if the rising incidence rates of ICC were due to increased detection in the absence of a true increase, they should plateau once the dissemination of testing has been achieved. The possibility of reclassification would be supported by an increase in the proportion of tumors with a confirmed tissue diagnosis. Lastly, the increasing incidence of ICC could be a reflection of increasing Journal of Hepatology 40 (2004) 472–477 www.elsevier.com/locate/jhep 0168-8278/$30.00 q 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jhep.2003.11.030 Received 8 July 2003; received in revised form 26 November 2003; accepted 27 November 2003 * Corresponding author. Tel.: þ1-713-794-8640; fax: þ 1-713-748-7359. E-mail address: hasheme@bcm.tmc.edu (H.B. El-Serag).