The incidence rates of cholangiocarcinoma (CC) vary greatly among different areas
of the world, and this variation is related to distribution of risk factors. Intrahepatic
cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) have different
epidemiological features. Recent data show that the incidence and mortality rates
of ICC have been increasing in several areas around the world. On the other hand,
the incidence and mortality rates of ECC have been decreasing. For example, in the
United States, the age-adjusted incidence rates of ICC increased by 165% from 0.32
per 100,000 in 1975 to 1979 to 0.85 per 100,000 in 1995 to 1999, whereas ECC declined
by 14%. In the meantime, there has been very little improvement in long-term survival,
which remains dismal (3.5%). Men are affected 1.5 times more than women are, and Asians
are affected almost 2 times more than whites and blacks. There are few well-established
risk factors for CC, including primary sclerosing cholangitis, liver fluke infestations,
hepatolithiasis, Thorotrast exposure, and choledochal cysts. None of these risk factors
can explain the recent increasing trends of ICC in the United States. Some data, however,
point to a potential role for chronic liver disease, hepatitis C, and probably hepatitis
B infections in the development of ICC.
KEYWORDS
Extrahepatic - survival - risk factors - incidence - SEER
REFERENCES
1
Vauthey J N, Blumgart L H.
Recent advances in the management of cholangiocarcinomas.
Semin Liver Dis.
1994;
14
109-114
2
Jemal A, Murray T, Samuels A et al..
Cancer statistics, 2003.
CA Cancer J Clin.
2003;
53
5-26
3
Mouzas I A, Dimoulios P, Vlachonikolis I G et al..
Increasing incidence of cholangiocarcinoma in Crete 1992-2000.
Anticancer Res.
2002;
22
3637-3641
4
Patel T.
Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the
United States.
Hepatology.
2001;
33
1353-1357
5
Patel T.
Worldwide trends in mortality from biliary tract malignancies.
BMC Cancer.
2002;
2
10
6
Taylor-Robinson S D, Toledano M B, Arora S et al..
Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales
1968-1998.
Gut.
2001;
48
816-820
7
Khan S A, Taylor-Robinson S D, Toledano M B et al..
Changing international trends in mortality rates for liver, biliary and pancreatic
tumours.
J Hepatol.
2002;
37
806-813
8
Shaib Y H, Davila J A, McGlynn K, El-Serag H B.
Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?.
J Hepatol.
2004;
40
472-477
9
Gumustop B, Aithal G P.
Striking trends in the cholangiocarcinoma incidence and mortality in the United States.
Gastroenterology.
2001;
120
A257
10 Strasberg S M, Drebin J A. Tumors of the biliary tree. In: Yamada T Textbook of
Gastroenterology. Philadelphia; Lippincott Williams & Wilkins 1999: 2326-2342
11
Okuda K, Nakanuma Y, Miyazaki M.
Cholangiocarcinoma: recent progress. Part 1: epidemiology and etiology.
J Gastroenterol Hepatol.
2002;
17
1049-1055
12
Altaee M Y, Johnson P J, Farrant J M, Williams R.
Etiologic and clinical characteristics of peripheral and hilar cholangiocarcinoma.
Cancer.
1991;
68
2051-2055
13
Cancer incidence in five continents.
IARC Scientific Publ.
1997;
7
i-xxxiv
1-1240
14
Parkin D M, Ohshima H, Srivatanakul P, Vatanasapt V.
Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention.
Cancer Epidemiol Biomarkers Prev.
1993;
2
537-544
15
de Groen P C, Gores G J, LaRusso N F, Gunderson L L, Nagorney D M.
Biliary tract cancers.
N Engl J Med.
1999;
341
1368-1378
16
Strom B L, Hibberd P L, Soper K A, Stolley P D, Nelson W L.
International variations in epidemiology of cancers of the extrahepatic biliary tract.
Cancer Res.
1985;
45
5165-5168
17
Carriaga M T, Henson D E.
Liver, gallbladder, extrahepatic bile ducts, and pancreas.
Cancer.
1995;
75(Suppl 1)
171-190
18 Nakanuma Y, Mashiso H, Tadashi T. Clinical and pathologic features of choalngiocarcinoma. In:
Okuda K, Tabor E Liver Cancer. New York; Churchill Livingstone 1997: 279-290
19
Bergquist A, Glaumann H, Persson B, Broome U.
Risk factors and clinical presentation of hepatobiliary carcinoma in patients with
primary sclerosing cholangitis: a case-control study.
Hepatology.
1998;
27
311-316
20
Chalasani N, Baluyut A, Ismail A et al..
Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter
case-control study.
Hepatology.
2000;
31
7-11
21
Broome U, Olsson R, Loof L et al..
Natural history and prognostic factors in 305 Swedish patients with primary sclerosing
cholangitis.
Gut.
1996;
38
610-615
22
Kornfeld D, Ekbom A, Ihre T.
Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis.
A population-based study.
Scand J Gastroenterol.
1997;
32
1042-1045
23
Aadland E, Schrumpf E, Fausa O et al..
Primary sclerosing cholangitis: a long-term follow-up study.
Scand J Gastroenterol.
1987;
22
655-664
24
Chapman R W, Arborgh B A, Rhodes J M et al..
Primary sclerosing cholangitis: a review of its clinical features, cholangiography,
and hepatic histology.
Gut.
1980;
21
870-877
25
Rosen C B, Nagorney D M, Wiesner R H, Coffey Jr R J, LaRusso N F.
Cholangiocarcinoma complicating primary sclerosing cholangitis.
Ann Surg.
1991;
213
21-25
26
Watanapa P, Watanapa W B.
Liver fluke-associated cholangiocarcinoma.
Br J Surg.
2002;
89
962-970
27
Abdel-Rahim A Y.
Parasitic infections and hepatic neoplasia.
Dig Dis.
2001;
19
288-291
28
Parkin D M, Srivatanakul P, Khlat M et al..
Liver cancer in Thailand. I. A case-control study of cholangiocarcinoma.
Int J Cancer.
1991;
48
323-328
29
Thamavit W, Bhamarapravati N, Sahaphong S, Vajrasthira S, Angsubhakorn S.
Effects of dimethylnitrosamine on induction of cholangiocarcinoma in Opisthorchis viverrini -infected Syrian golden hamsters.
Cancer Res.
1978;
38
4634-4639
30
Thamavit W, Kongkanuntn R, Tiwawech D, Moore M A.
Level of Opisthorchis infestation and carcinogen dose-dependence of cholangiocarcinoma induction in Syrian
golden hamsters.
Virchows Arch B Cell Pathol Incl Mol Pathol.
1987;
54
52-58
31
Shin H R, Lee C U, Park H J et al..
Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea.
Int J Epidemiol.
1996;
25
933-940
32
Huang M J, Liaw Y F, Wu C S.
Comparison of intravenous radionuclide cholescintigraphy and endoscopic retrograde
cholangiography in the diagnosis of intrahepatic gall-stones.
Br J Radiol.
1981;
54
302-306
33
Chen M F.
Peripheral cholangiocarcinoma (cholangiocellular carcinoma): clinical features, diagnosis
and treatment.
J Gastroenterol Hepatol.
1999;
14
1144-1149
34
Okuda K, Kubo Y, Okazaki N, Arishima T, Hashimoto M.
Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma: a
study of 57 autopsy-proven cases.
Cancer.
1977;
39
232-246
35
Tabata M, Nakayama F.
Bacteria and gallstones. Etiological significance.
Dig Dis Sci.
1981;
26
218-224
36 Simeone D M. Gallbladder and biliary tree: anatomy and structural anomalies. In:
Yamada T Textbook of Gastroenterology. Philadelphia; Lippincott Williams & Wilkins
1999: 2244-2257
37
Chijiiwa K, Koga A.
Surgical management and long-term follow-up of patients with choledochal cysts.
Am J Surg.
1993;
165
238-242
38
Lipsett P A, Pitt H A, Colombani P M, Boitnott J K, Cameron J L.
Choledochal cyst disease. A changing pattern of presentation.
Ann Surg.
1994;
220
644-652
39
Ohtsuka T, Inoue K, Ohuchida J et al..
Carcinoma arising in choledochocele.
Endoscopy.
2001;
33
614-619
40
Hardell L, Bengtsson N O, Jonsson U, Eriksson S, Larsson L G.
Aetiological aspects on primary liver cancer with special regard to alcohol, organic
solvents and acute intermittent porphyria-an epidemiological investigation.
Br J Cancer.
1984;
50
389-397
41
Donato F, Gelatti U, Tagger A et al..
Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake,
and hepatolithiasis: a case-control study in Italy.
Cancer Causes Control.
2001;
12
959-964
42
Kobayashi M, Ikeda K, Saitoh S et al..
Incidence of primary cholangiocellular carcinoma of the liver in japanese patients
with hepatitis C virus-related cirrhosis.
Cancer.
2000;
88
2471-2477
43
Sorensen H T, Friis S, Olsen J H et al..
Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort
study in Denmark.
Hepatology.
1998;
28
921-925
44
Yin F, Chen B.
Detection of hepatitis C virus RNA sequences in hepatic portal cholangiocarcinoma
tissue by reverse transcription polymerase chain reaction.
Chin Med J (Engl).
1998;
111
1068-1070
45
Songsivilai S, Dharakul T, Kanistanon D.
Hepatitis C virus genotypes in patients with hepatocellular carcinoma and cholangiocarcinoma
in Thailand.
Trans R Soc Trop Med Hyg.
1996;
90
505-507
46
Wiesner R H, LaRusso N F.
Clinicopathologic features of the syndrome of primary sclerosing cholangitis.
Gastroenterology.
1980;
79
200-206
Hashem B El-SeragM.D.
The Houston Veterans Affairs Medical Center
2002 Holcombe Blvd (152)
Houston, TX 77030
eMail: hasheme@bcm.tmc.edu