Epidemiology of Primary and Secondary Liver Cancers

Ashwin Ananthakrishnan; Veena Gogineni; Kia Saeian

doi:10.1055/s-2006-939841

Seminars in Interventional Radiology, Inhaltsverzeichnis

Semin intervent Radiol 2006; 23(1): 047-063
DOI: 10.1055/s-2006-939841

Epidemiology of Primary and Secondary Liver Cancers

Ashwin Ananthakrishnan¹ , Veena Gogineni¹ , Kia Saeian¹

¹Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin

Abstract

ABSTRACT

Primary liver cancer is the sixth most common cancer worldwide with a wide geographic distribution. The incidence of primary liver cancer is increasing and there is still a higher prevalence in developing countries. Early recognition remains an obstacle and lack of it results in poor outcomes for hepatocellular carcinoma (HCC), the most prevalent primary liver cancer, and cholangiocarcinoma. The most common risk factors associated with HCC are hepatitis B and chronic hepatitis C infections, alcohol use, smoking, and aflatoxin exposure. Emerging risk factors such as obesity might play an important role in the future because of the increasing prevalence of this condition.

KEYWORDS

Primary liver cancer - hepatocellular carcinoma - cholangiocarcinoma - chronic hepatitis B - chronic hepatitis C

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REFERENCES

1 El-Serag H B. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol. 2002; 35 S72-S78
2 Lenhard R, Osteen RT, Gansler T Clinical Oncology. Atlanta, GA; Blackwell Publishing, Inc 2001
3 Parkin D M, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55 74-108
4 McGlynn K A, Tsao L, Hsing A W, Devesa S S, Fraumeni Jr J F. International trends and patterns of primary liver cancer. Int J Cancer. 2001; 94 290-296
5 Kew M C. Hepatic tumors and cysts. In: Feldman M, Friedman LS, Sleisenger MH, Scharschmidt BF Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. Philadelphia; Saunders 2002: 1583-1588
6 Fong Y, Kemeny N, Lawrence T S. Cancer of the liver and biliary tree. In: Devita VT, Hellman S, Rosenberg SA Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia; Lippincott Williams and Wilkins 2001: 1162-1187
7 Kiyosawa K, Umemura T, Ichijo T et al.. Hepatocellular carcinoma: recent trends in Japan. Gastroenterology. 2004; 127 S17-S26
8 Bosch F X, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004; 127 S5-S16
9 Ries LAG, Eisner MP, Kosary CL, et al SEER Cancer Statistics Review, 1975-2002. Bethesda, MD; National Cancer Institute 2005 Available at: http://seer.cancer.gov/csr/1975_2002
10 Surveillance, Epidemiology, and End Results (SEER) Program .http://Available at: www.seer.cancer.gov SEER*Stat Databases. Incidence-SEER 13 Regs Public-Use, Nov 2004 Sub for Expanded Races (1992-2002) and Incidence-SEER 13 Regs excluding AK Public-Use, Nov 2004 Sub for Hispanics (1992-2002), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch released April 2005, based on the November 2004 submission.
11 Di Bisceglie A M, Order S E, Klein J L et al.. The role of chronic viral hepatitis in hepatocellular carcinoma in the United States. Am J Gastroenterol. 1991; 86 335-338
12 Hassan M M, Frome A, Patt Y Z, El-Serag H B. Rising prevalence of hepatitis C virus infection among patients recently diagnosed with hepatocellular carcinoma in the United States. J Clin Gastroenterol. 2002; 35 266-269
13 Godley P A, Sandler R S. Liver cancer. In: Everhart JE Digestive Diseases in United States: Epidemiology and Impact. Washington, DC; Government Printing Office 1994: 227-241
14 Kew M C. Hepatic tumors and cysts. In: Feldman M, Friedman LS, Sleisenger MH, Scharschmidt BF Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. Philadelphia; Saunders 2002: 1577-1602
15 Takano S, Yokosuka O, Imazeki F, Tagawa M, Omata M. Incidence of hepatocellular carcinoma in chronic hepatitis B and C: a prospective study of 251 patients. Hepatology. 1995; 21 650-655
16 Castells L, Vargas V, Gonzalez A, Esteban J, Esteban R, Guardia J. Long interval between HCV infection and development of hepatocellular carcinoma. Liver. 1995; 15 159-163
17 Sherlock S. Viruses and hepatocellular carcinoma. Gut. 1994; 35 828-832
18 Yarrish R L, Werner B G, Blumberg B S. Association of hepatitis B virus infection with hepatocellular carcinoma in American patients. Int J Cancer. 1980; 26 711-715
19 Alter M J. Epidemiology of hepatitis C. Hepatology. 1997; 26 62S-65S
20 Kelen G D, Green G B, Purcell R H et al.. Hepatitis B and hepatitis C in emergency department patients. N Engl J Med. 1992; 326 1399-1404
21 McQuillan G M, Alter M J, Everhart J E. Viral hepatitis. In: Everhart JE Digestive Diseases in the United States: Epidemiology and Impact. Washington, DC; Government Printing Office 1994: 127-156
22 Centers for Disease Control and Prevention (CDC) . Incidence of acute hepatitis B: United States, 1990-2002. MMWR Morb Mortal Wkly Rep. 2004; 52 1252-1254
23 Feitelson M A. Hepatitis B virus in hepatocarcinogenesis. J Cell Physiol. 1999; 181 188-202
24 Shimada M, Rikimaru T, Sugimachi K et al.. The importance of hepatic resection for hepatocellular carcinoma originating from nonfibrotic liver. J Am Coll Surg. 2000; 191 531-537
25 Di Bisceglie A M, Rustgi V K, Hoofnagle J H, Dusheiko G M, Lotze M T. NIH conference: hepatocellular carcinoma. Ann Intern Med. 1988; 108 390-401
26 Chang M H, Shau W Y, Chen C J et al.. Hepatitis B vaccination and hepatocellular carcinoma rates in boys and girls. JAMA. 2000; 284 3040-3042
27 Armstrong G L, Alter M J, McQuillan G M, Margolis H S. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology. 2000; 31 777-782
28 Davis G L, Balart L A, Schiff E R et al.. Treatment of chronic hepatitis C with recombinant interferon alfa: a multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Engl J Med. 1989; 321 1501-1506
29 Di Bisceglie A M, Martin P, Kassianides C et al.. Recombinant interferon alfa therapy for chronic hepatitis C: a randomized, double-blind, placebo-controlled trial. N Engl J Med. 1989; 321 1506-1510
30 Manns M P, McHutchison J G, Gordon S C et al.. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001; 358 958-965
31 McHutchison J G, Gordon S C, Schiff E R et al.. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. 1998; 339 1485-1492
32 Ikeda K, Kobayashi M, Saitoh S et al.. Significance of hepatitis B virus DNA clearance and early prediction of hepatocellular carcinogenesis in patients with cirrhosis undergoing interferon therapy: long-term follow up of a pilot study. J Gastroenterol Hepatol. 2005; 20 95-102
33 Ikeda K, Saitoh S, Suzuki Y et al.. Interferon decreases hepatocellular carcinogenesis in patients with cirrhosis caused by the hepatitis B virus: a pilot study. Cancer. 1998; 82 827-835
34 Mazzella G, Accogli E, Sottili S et al.. Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis. J Hepatol. 1996; 24 141-147
35 Oon C J. Long-term survival following treatment of hepatocellular carcinoma in Singapore: evaluation of Wellferon in the prophylaxis of high-risk pre-cancerous conditions. Cancer Chemother Pharmacol. 1992; 31(suppl) S137-S142
36 Wong J B, Koff R S, Tine F, Pauker S G. Cost-effectiveness of interferon-alpha 2b treatment for hepatitis B e antigen-positive chronic hepatitis B. Ann Intern Med. 1995; 122 664-675
37 Dienstag J L, Perrillo R P, Schiff E R, Bartholomew M, Vicary C, Rubin M. A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med. 1995; 333 1657-1661
38 Dienstag J L, Schiff E R, Wright T L et al.. Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med. 1999; 341 1256-1263
39 Lai C L, Chien R N, Leung N W et al.. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med. 1998; 339 61-68
40 Walsh K M, Woodall T, Lamy P, Wight D G, Bloor S, Alexander G J. Successful treatment with adefovir dipivoxil in a patient with fibrosing cholestatic hepatitis and lamivudine resistant hepatitis B virus. Gut. 2001; 49 436-440
41 de Man R A, Wolters L M, Nevens F et al.. Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection. Hepatology. 2001; 34 578-582
42 Hassan M M, Hwang L Y, Hatten C J et al.. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology. 2002; 36 1206-1213
43 Jee S H, Ohrr H, Sull J W, Samet J M. Cigarette smoking, alcohol drinking, hepatitis B, and risk for hepatocellular carcinoma in Korea. J Natl Cancer Inst. 2004; 96 1851-1856
44 La Vecchia C, Negri E, Decarli A, D'Avanzo B, Franceschi S. Risk factors for hepatocellular carcinoma in northern Italy. Int J Cancer. 1988; 42 872-876
45 Marrero J A, Fontana R J, Fu S, Conjeevaram H S, Su G L, Lok A S. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J Hepatol. 2005; 42 218-224
46 Mayans M V, Calvet X, Bruix J et al.. Risk factors for hepatocellular carcinoma in Catalonia, Spain. Int J Cancer. 1990; 46 378-381
47 Sun C A, Wu D M, Lin C C et al.. Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: a prospective study of 12,008 men in Taiwan. Am J Epidemiol. 2003; 157 674-682
48 Yu M C, Tong M J, Govindarajan S, Henderson B E. Nonviral risk factors for hepatocellular carcinoma in a low-risk population, the non-Asians of Los Angeles County, California. J Natl Cancer Inst. 1991; 83 1820-1826
49 Yuan J M, Govindarajan S, Arakawa K, Yu M C. Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the US. Cancer. 2004; 101 1009-1017
50 Braga C, La Vecchia C, Negri E, Franceschi S. Attributable risks for hepatocellular carcinoma in northern Italy. Eur J Cancer. 1997; 33 629-634
51 Donato F, Tagger A, Chiesa R et al.. Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy. Brescia HCC Study. Hepatology. 1997; 26 579-584
52 Tsutsumi M, Ishizaki M, Takada A. Relative risk for the development of hepatocellular carcinoma in alcoholic patients with cirrhosis: a multiple logistic-regression coefficient analysis. Alcohol Clin Exp Res. 1996; 20 758-762
53 Tsukuma H, Hiyama T, Oshima A et al.. A case-control study of hepatocellular carcinoma in Osaka, Japan. Int J Cancer. 1990; 45 231-236
54 Donato F, Tagger A, Gelatti U et al.. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol. 2002; 155 323-331
55 Tanaka K, Hirohata T, Takeshita S et al.. Hepatitis B virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: a case-control study in Fukuoka, Japan. Int J Cancer. 1992; 51 509-514
56 Evans A A, Chen G, Ross E A, Shen F M, Lin W Y, London W T. Eight-year follow-up of the 90,000-person Haimen City cohort. I: hepatocellular carcinoma mortality, risk factors, and gender differences. Cancer Epidemiol Biomarkers Prev. 2002; 11 369-376
57 Zhang J Y, Wang X, Han S G, Zhuang H. A case-control study of risk factors for hepatocellular carcinoma in Henan, China. Am J Trop Med Hyg. 1998; 59 947-951
58 Goritsas C P, Athanasiadou A, Arvaniti A, Lampropoulou-Karatza C. The leading role of hepatitis B and C viruses as risk factors for the development of hepatocellular carcinoma: a case control study. J Clin Gastroenterol. 1995; 20 220-224
59 Naccarato R, Farinati F. Hepatocellular carcinoma, alcohol, and cirrhosis: facts and hypotheses. Dig Dis Sci. 1991; 36 1137-1142
60 Bralet M P, Regimbeau J M, Pineau P et al.. Hepatocellular carcinoma occurring in nonfibrotic liver: epidemiologic and histopathologic analysis of 80 French cases. Hepatology. 2000; 32 200-204
61 Chiesa R, Donato F, Tagger A et al.. Etiology of hepatocellular carcinoma in Italian patients with and without cirrhosis. Cancer Epidemiol Biomarkers Prev. 2000; 9 213-216
62 Grando-Lemaire V, Guettier C, Chevret S, Beaugrand M, Trinchet J C. Hepatocellular carcinoma without cirrhosis in the West: epidemiological factors and histopathology of the non-tumorous liver. Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire. J Hepatol. 1999; 31 508-513
63 Cordier S, Le T B, Verger P et al.. Viral infections and chemical exposures as risk factors for hepatocellular carcinoma in Vietnam. Int J Cancer. 1993; 55 196-201
64 Yu M W, Hsu F C, Sheen I S et al.. Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. Am J Epidemiol. 1997; 145 1039-1047
65 Kuper H, Tzonou A, Kaklamani E et al.. Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer. 2000; 85 498-502
66 Mastrangelo G, Fedeli U, Fadda E et al.. Increased risk of hepatocellular carcinoma and liver cirrhosis in vinyl chloride workers: synergistic effect of occupational exposure with alcohol intake. Environ Health Perspect. 2004; 112 1188-1192
67 Bradbear R A, Bain C, Siskind V et al.. Cohort study of internal malignancy in genetic hemochromatosis and other chronic nonalcoholic liver diseases. J Natl Cancer Inst. 1985; 75 81-84
68 Hsing A W, McLaughlin J K, Olsen J H, Mellemkjar L, Wacholder S, Fraumeni Jr J F. Cancer risk following primary hemochromatosis: a population-based cohort study in Denmark. Int J Cancer. 1995; 60 160-162
69 Davila J A, Morgan R O, Shaib Y, McGlynn K A, El-Serag H B. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut. 2005; 54 533-539
70 El-Serag H B, Richardson P A, Everhart J E. The role of diabetes in hepatocellular carcinoma: a case-control study among United States Veterans. Am J Gastroenterol. 2001; 96 2462-2467
71 Cauza E, Peck-Radosavljevic M, Ulrich-Pur H et al.. Mutations of the HFE gene in patients with hepatocellular carcinoma. Am J Gastroenterol. 2003; 98 442-447
72 Elmberg M, Hultcrantz R, Ekbom A et al.. Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives. Gastroenterology. 2003; 125 1733-1741
73 Gelatti U, Donato F, Tagger A et al.. Etiology of hepatocellular carcinoma influences clinical and pathologic features but not patient survival. Am J Gastroenterol. 2003; 98 907-914
74 Fracanzani A L, Conte D, Fraquelli M et al.. Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non-iron-related chronic liver disease. Hepatology. 2001; 33 647-651
75 Blumberg R S, Chopra S, Ibrahim R et al.. Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis. Gastroenterology. 1988; 95 1399-1402
76 Deugnier Y M, Guyader D, Crantock L et al.. Primary liver cancer in genetic hemochromatosis: a clinical, pathological, and pathogenetic study of 54 cases. Gastroenterology. 1993; 104 228-234
77 Goh J, Callagy G, McEntee G, O'Keane J C, Bomford A, Crowe J. Hepatocellular carcinoma arising in the absence of cirrhosis in genetic haemochromatosis: three case reports and review of literature. Eur J Gastroenterol Hepatol. 1999; 11 915-919
78 Thompson N P, Stansby G, Jarmulowicz M, Hobbs K E, McIntyre N. Hepatocellular carcinoma arising in non-cirrhotic haemochromatosis. HPB Surg. 1995; 8 163-166
79 Fellows I W, Stewart M, Jeffcoate W J, Smith P G, Toghill P J. Hepatocellular carcinoma in primary haemochromatosis in the absence of cirrhosis. Gut. 1988; 29 1603-1606
80 Boige V, Castera L, de Roux N et al.. Lack of association between HFE gene mutations and hepatocellular carcinoma in patients with cirrhosis. Gut. 2003; 52 1178-1181
81 Racchi O, Mangerini R, Rapezzi D et al.. Mutations of the HFE gene and the risk of hepatocellular carcinoma. Blood Cells Mol Dis. 1999; 25 350-353
82 Fargion S, Stazi M A, Fracanzani A L et al.. Mutations in the HFE gene and their interaction with exogenous risk factors in hepatocellular carcinoma. Blood Cells Mol Dis. 2001; 27 505-511
83 Hellerbrand C, Poppl A, Hartmann A, Scholmerich J, Lock G. HFE C282Y heterozygosity in hepatocellular carcinoma: evidence for an increased prevalence. Clin Gastroenterol Hepatol. 2003; 1 279-284
84 Lauret E, Rodriguez M, Gonzalez S et al.. HFE gene mutations in alcoholic and virus-related cirrhotic patients with hepatocellular carcinoma. Am J Gastroenterol. 2002; 97 1016-1021
85 Pirisi M, Toniutto P, Uzzau A et al.. Carriage of HFE mutations and outcome of surgical resection for hepatocellular carcinoma in cirrhotic patients. Cancer. 2000; 89 297-302
86 Fargion S, Piperno A, Fracanzani A L, Cappellini M D, Romano R, Fiorelli G. Iron in the pathogenesis of hepatocellular carcinoma. Ital J Gastroenterol. 1991; 23 584-588
87 Mallory M A, Kowdley K V. Hereditary hemochromatosis and cancer risk: more fuel to the fire?. Gastroenterology. 2001; 121 1253-1254
88 Wang X W, Hussain S P, Huo T I et al.. Molecular pathogenesis of human hepatocellular carcinoma. Toxicology. 2002; 181-182 43-47
89 Deugnier Y, Turlin B. Iron and hepatocellular carcinoma. J Gastroenterol Hepatol. 2001; 16 491-494
90 Hatch M C, Chen C J, Levin B et al.. Urinary aflatoxin levels, hepatitis-B virus infection and hepatocellular carcinoma in Taiwan. Int J Cancer. 1993; 54 931-934
91 Van Rensburg S J, Cook-Mozaffari P, Van Schalkwyk D J, Van der Watt J J, Vincent T J, Purchase I F. Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei. Br J Cancer. 1985; 51 713-726
92 Yeh F S, Yu M C, Mo C C, Luo S, Tong M J, Henderson B E. Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China. Cancer Res. 1989; 49 2506-2509
93 Omer R E, Kuijsten A, Kadaru A M et al.. Population-attributable risk of dietary aflatoxins and hepatitis B virus infection with respect to hepatocellular carcinoma. Nutr Cancer. 2004; 48 15-21
94 Wang J S, Qian G S, Zarba A et al.. Temporal patterns of aflatoxin-albumin adducts in hepatitis B surface antigen-positive and antigen-negative residents of Daxin, Qidong County, People's Republic of China. Cancer Epidemiol Biomarkers Prev. 1996; 5 253-261
95 Groopman J D. Do aflatoxin-DNA adduct measurements in humans provide accurate data for cancer risk assessment?. IARC Sci Publ. 1988; (89) 55-62
96 Chen C J, Wang L Y, Lu S N et al.. Elevated aflatoxin exposure and increased risk of hepatocellular carcinoma. Hepatology. 1996; 24 38-42
97 Ross R K, Yuan J M, Yu M C et al.. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet. 1992; 339 943-946
98 Lin L, Yang F, Ye Z et al.. Case-control study of cigarette smoking and primary hepatoma in an aflatoxin-endemic region of China: a protective effect. Pharmacogenetics. 1991; 1 79-85
99 Sun Z, Lu P, Gail M H et al.. Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1. Hepatology. 1999; 30 379-383
100 Wang L Y, Hatch M, Chen C J et al.. Aflatoxin exposure and risk of hepatocellular carcinoma in Taiwan. Int J Cancer. 1996; 67 620-625
101 Kew M C. Synergistic interaction between aflatoxin B1 and hepatitis B virus in hepatocarcinogenesis. Liver Int. 2003; 23 405-409
102 Wojnowski L, Turner P C, Pedersen B et al.. Increased levels of aflatoxin-albumin adducts are associated with CYP3A5 polymorphisms in The Gambia, West Africa. Pharmacogenetics. 2004; 14 691-700
103 Kubicka S, Trautwein C, Niehof M, Manns M. Target gene modulation in hepatocellular carcinomas by decreased DNA-binding of p53 mutations. Hepatology. 1997; 25 867-873
104 Aguilar F, Hussain S P, Cerutti P. Aflatoxin B1 induces the transversion of G→T in codon 249 of the p53 tumor suppressor gene in human hepatocytes. Proc Natl Acad Sci USA. 1993; 90 8586-8590
105 Hsu I C, Metcalf R A, Sun T, Welsh J A, Wang N J, Harris C C. Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature. 1991; 350 427-428
106 Kirk G D, Camus-Randon A M, Mendy M et al.. Ser-249 p53 mutations in plasma DNA of patients with hepatocellular carcinoma from The Gambia. J Natl Cancer Inst. 2000; 92 148-153
107 Adami H O, Chow W H, Nyren O et al.. Excess risk of primary liver cancer in patients with diabetes mellitus. J Natl Cancer Inst. 1996; 88 1472-1477
108 Lu S N, Lin T M, Chen C J et al.. A case-control study of primary hepatocellular carcinoma in Taiwan. Cancer. 1988; 62 2051-2055
109 Lawson D H, Gray J M, McKillop C, Clarke J, Lee F D, Patrick R S. Diabetes mellitus and primary hepatocellular carcinoma. Q J Med. 1986; 61 945-955
110 Matsuo M. Association between diabetes mellitus and hepatocellular carcinoma: results of a hospital- and community-based case-control study. Kurume Med J. 2003; 50 91-98
111 Regimbeau J M, Colombat M, Mognol P et al.. Obesity and diabetes as a risk factor for hepatocellular carcinoma. Liver Transpl. 2004; 10 S69-S73
112 El-Serag H B, Tran T, Everhart J E. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology. 2004; 126 460-468
113 Lagiou P, Kuper H, Stuver S O, Tzonou A, Trichopoulos D, Adami H O. Role of diabetes mellitus in the etiology of hepatocellular carcinoma. J Natl Cancer Inst. 2000; 92 1096-1099
114 Tolman K G, Fonseca V, Tan M H, Dalpiaz A. Narrative review: hepatobiliary disease in type 2 diabetes mellitus. Ann Intern Med. 2004; 141 946-956
115 Tazawa J, Maeda M, Nakagawa M et al.. Diabetes mellitus may be associated with hepatocarcinogenesis in patients with chronic hepatitis C. Dig Dis Sci. 2002; 47 710-715
116 IARC Working Group on the Evaluation of Carcinogenic Risks to Humans . Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum. 2004; 83 1-1438
117 Trichopoulos D, Day N E, Kaklamani E et al.. Hepatitis B virus, tobacco smoking and ethanol consumption in the etiology of hepatocellular carcinoma. Int J Cancer. 1987; 39 45-49
118 Trichopoulos D, MacMahon B, Sparros L, Merikas G. Smoking and hepatitis B-negative primary hepatocellular carcinoma. J Natl Cancer Inst. 1980; 65 111-114
119 Lam K C, Yu M C, Leung J W, Henderson B E. Hepatitis B virus and cigarette smoking: risk factors for hepatocellular carcinoma in Hong Kong. Cancer Res. 1982; 42 5246-5248
120 Gelatti U, Covolo L, Talamini R et al.. N-Acetyltransferase-2, glutathione S-transferase M1 and T1 genetic polymorphisms, cigarette smoking and hepatocellular carcinoma: a case-control study. Int J Cancer. 2005; 115 301-306
121 Mori M, Hara M, Wada I et al.. Prospective study of hepatitis B and C viral infections, cigarette smoking, alcohol consumption, and other factors associated with hepatocellular carcinoma risk in Japan. Am J Epidemiol. 2000; 151 131-139
122 Pyong S J, Tsukuma H, Hiyama T. Case-control study of hepatocellular carcinoma among Koreans living in Osaka, Japan. Jpn J Cancer Res. 1994; 85 674-679
123 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
124 Tsukuma H, Hiyama T, Tanaka S et al.. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993; 328 1797-1801
125 Oshima A, Tsukuma H, Hiyama T, Fujimoto I, Yamano H, Tanaka M. Follow-up study of HBs Ag-positive blood donors with special reference to effect of drinking and smoking on development of liver cancer. Int J Cancer. 1984; 34 775-779
126 Chiba T, Matsuzaki Y, Abei M et al.. The role of previous hepatitis B virus infection and heavy smoking in hepatitis C virus-related hepatocellular carcinoma. Am J Gastroenterol. 1996; 91 1195-1203
127 Chen S Y, Wang L Y, Lunn R M et al.. Polycyclic aromatic hydrocarbon-DNA adducts in liver tissues of hepatocellular carcinoma patients and controls. Int J Cancer. 2002; 99 14-21
128 Yu M W, Pai C I, Yang S Y et al.. Role of N-acetyltransferase polymorphisms in hepatitis B related hepatocellular carcinoma: impact of smoking on risk. Gut. 2000; 47 703-709
129 Younossi Z M, McCullough A J, Ong J P et al.. Obesity and non-alcoholic fatty liver disease in chronic hepatitis C. J Clin Gastroenterol. 2004; 38 705-709
130 Anagnostopoulos G K, Arvanitidis D, Tsiakos S, Margantinis G, Grigoriadis K, Kostopoulos P. Is hepatocellular carcinoma part of the natural history of nonalcoholic steatohepatitis?. J Clin Gastroenterol. 2003; 37 88-89
131 Bencheqroun R, Duvoux C, Luciani A, Zafrani E S, Dhumeaux D. [Hepatocellular carcinoma without cirrhosis in a patient with nonalcoholic steatohepatitis]. Gastroenterol Clin Biol. 2004; 28 497-499
132 Bullock R E, Zaitoun A M, Aithal G P, Ryder S D, Beckingham I J, Lobo D N. Association of non-alcoholic steatohepatitis without significant fibrosis with hepatocellular carcinoma. J Hepatol. 2004; 41 685-686
133 Cuadrado A, Orive A, Garcia-Suarez C et al.. Non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma. Obes Surg. 2005; 15 442-446
134 Marrero J A, Fontana R J, Su G L, Conjeevaram H S, Emick D M, Lok A S. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology. 2002; 36 1349-1354
135 Mori S, Yamasaki T, Sakaida I et al.. Hepatocellular carcinoma with nonalcoholic steatohepatitis. J Gastroenterol. 2004; 39 391-396
136 Orikasa H, Ohyama R, Tsuka N, Eyden B P, Yamazaki K. Lipid-rich clear-cell hepatocellular carcinoma arising in non-alcoholic steatohepatitis in a patient with diabetes mellitus. J Submicrosc Cytol Pathol. 2001; 33 195-200
137 Shimada M, Hashimoto E, Taniai M et al.. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. J Hepatol. 2002; 37 154-160
138 Yoshioka Y, Hashimoto E, Yatsuji S et al.. Nonalcoholic steatohepatitis: cirrhosis, hepatocellular carcinoma, and burnt-out NASH. J Gastroenterol. 2004; 39 1215-1218
139 Zen Y, Katayanagi K, Tsuneyama K, Harada K, Araki I, Nakanuma Y. Hepatocellular carcinoma arising in non-alcoholic steatohepatitis. Pathol Int. 2001; 51 127-131
140 Hashimoto E, Taniai M, Kaneda H et al.. Comparison of hepatocellular carcinoma patients with alcoholic liver disease and nonalcoholic steatohepatitis. Alcohol Clin Exp Res. 2004; 28 164S-168S
141 Yang S, Lin H Z, Hwang J, Chacko V P, Diehl A M. Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition?. Cancer Res. 2001; 61 5016-5023
142 Lonardo A, Bagni A, Tarugi P, Loria P. The wide spectrum of steatohepatitis: a report of four cases and a review of the literature. Eur J Gastroenterol Hepatol. 2004; 16 1043-1050
143 Nair S, Mason A, Eason J, Loss G, Perrillo R P. Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis?. Hepatology. 2002; 36 150-155
144 Ratziu V, Bonyhay L, Di Martino V et al.. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis. Hepatology. 2002; 35 1485-1493
145 Caldwell S H, Crespo D M, Kang H S, Al-Osaimi A M. Obesity and hepatocellular carcinoma. Gastroenterology. 2004; 127 S97-103
146 Huo T I, Wu J C, Lee S D. Are alcohol, tobacco and obesity genuine risk factors for hepatocellular carcinoma?. J Hepatol. 2005; 42 941
147 Suriawinata A, Fiel M I. Liver pathology in obesity. Semin Liver Dis. 2004; 24 363-370
148 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
149 Parkin D M, Ohshima H, Srivatanakul P, Vatanasapt V. Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention. Cancer Epidemiol Biomarkers Prev. 1993; 2 537-544
150 Shaib Y H, El-Serag H B, Davila J A, Morgan R, McGlynn K A. Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study. Gastroenterology. 2005; 128 620-626
151 Kuper H, Lagiou P, Mucci L A, Tamimi R, Benetou V, Trichopoulos D. Risk factors for cholangiocarcinoma in a low risk Caucasian population. Soz Praventivmed. 2001; 46 182-185
152 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
153 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
154 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
155 Su W C, Chan K K, Lin X Z et al.. A clinical study of 130 patients with biliary tract cancers and periampullary tumors. Oncology. 1996; 53 488-493
156 Pinyosophon A, Wiwanitkit V. The prevalence of hepatitis B seropositivity among patients with cholangiocarcinoma. Viral Immunol. 2002; 15 655-657
157 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
158 Yamamoto S, Kubo S, Hai S et al.. Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma. Cancer Sci. 2004; 95 592-595
159 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
160 Lu H, Ye M Q, Thung S N, Dash S, Gerber M A. Detection of hepatitis C virus RNA sequences in cholangiocarcinomas in Chinese and American patients. Chin Med J (Engl). 2000; 113 1138-1141
161 Polizos A, Kelekis N, Sinani C, Patsiaoura K, Papadamou G, Dalekos G N. Advanced intrahepatic cholangiocarcinoma in hepatitis C virus-related decompensated cirrhosis: case report and review of the literature. Eur J Gastroenterol Hepatol. 2003; 15 331-334
162 Bergquist A, Ekbom A, Olsson R et al.. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol. 2002; 36 321-327
163 Boberg K M, Bergquist A, Mitchell S et al.. Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation. Scand J Gastroenterol. 2002; 37 1205-1211
164 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
165 Burak K, Angulo P, Pasha T M, Egan K, Petz J, Lindor K D. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol. 2004; 99 523-526
166 Ponsioen C Y, Vrouenraets S M, Prawirodirdjo W et al.. Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population. Gut. 2002; 51 562-566
167 Bjornsson E, Boberg K M, Cullen S et al.. Patients with small duct primary sclerosing cholangitis have a favourable long term prognosis. Gut. 2002; 51 731-735
168 Boberg K M, Schrumpf E, Bergquist A et al.. Cholangiocarcinoma in primary sclerosing cholangitis: K-ras mutations and Tp53 dysfunction are implicated in the neoplastic development. J Hepatol. 2000; 32 374-380
169 Boberg K M, Spurkland A, Rocca G et al.. The HLA-DR3,DQ2 heterozygous genotype is associated with an accelerated progression of primary sclerosing cholangitis. Scand J Gastroenterol. 2001; 36 886-890
170 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
171 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
172 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
173 International Agency for Research on Cancer Working Group . Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis). IARC Monogr Eval Carcinog Risks Hum. 1994; 61 121-175
174 Schwartz D A. Cholangiocarcinoma associated with liver fluke infection: a preventable source of morbidity in Asian immigrants. Am J Gastroenterol. 1986; 81 76-79
175 Stauffer W M, Sellman J S, Walker P F. Biliary liver flukes (Opisthorchiasis and Clonorchiasis) in immigrants in the United States: often subtle and diagnosed years after arrival. J Travel Med. 2004; 11 157-159
176 Chapman R W. Risk factors for biliary tract carcinogenesis. Ann Oncol. 1999; 10(suppl 4) 308-311
177 Choi B I, Han J K, Hong S T, Lee K H. Clonorchiasis and cholangiocarcinoma: etiologic relationship and imaging diagnosis. Clin Microbiol Rev. 2004; 17 540-552
178 Hong S T, Kho W G, Kim W H, Chai J Y, Lee S H. Turnover of biliary epithelial cells in Clonorchis sinensis infected rats. Korean J Parasitol. 1993; 31 83-89
179 Hou P C. The relationship between primary carcinoma of the liver and infestation with Clonorchis sinensis . J Pathol Bacteriol. 1956; 72 239-246
180 Sriamporn S, Pisani P, Pipitgool V, Suwanrungruang K, Kamsa-ard S, Parkin D M. Prevalence of Opisthorchis viverrini infection and incidence of cholangiocarcinoma in Khon Kaen, Northeast Thailand. Trop Med Int Health. 2004; 9 588-594
181 Pairojkul C, Shirai T, Hirohashi S et al.. Multistage carcinogenesis of liver-fluke-associated cholangiocarcinoma in Thailand. Princess Takamatsu Symp. 1991; 22 77-86
182 Haswell-Elkins M R, Mairiang E, Mairiang P et al.. Cross-sectional study of Opisthorchis viverrini infection and cholangiocarcinoma in communities within a high-risk area in northeast Thailand. Int J Cancer. 1994; 59 505-509
183 Itoh M, Pairojkul C, Thamawit W et al.. Association of antibodies to Opisthorchis viverrini with hepatobiliary disease in northeastern Thailand. Am J Trop Med Hyg. 1994; 51 424-429
184 Pinlaor S, Hiraku Y, Ma N et al.. Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis. Nitric Oxide. 2004; 11 175-183
185 Pinlaor S, Tada-Oikawa S, Hiraku Y et al.. Opisthorchis viverrini antigen induces the expression of Toll-like receptor 2 in macrophage RAW cell line. Int J Parasitol. 2005; 35 591-596
186 Lee C C, Wu C Y, Chen G H. What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma?. J Gastroenterol Hepatol. 2002; 17 1015-1020
187 Chen D W, Tung-Ping Poon R, Liu C L, Fan S T, Wong J. Immediate and long-term outcomes of hepatectomy for hepatolithiasis. Surgery. 2004; 135 386-393
188 Chen M F, Jan Y Y, Wang C S et al.. A reappraisal of cholangiocarcinoma in patient with hepatolithiasis. Cancer. 1993; 71 2461-2465
189 Chijiiwa K, Ohtani K, Noshiro H et al.. Cholangiocellular carcinoma depending on the kind of intrahepatic calculi in patients with hepatolithiasis. Hepatogastroenterology. 2002; 49 96-99
190 Wang Y J, Lee S D, Shyu J K, Lo K J. Clinical experience in 126 patients with tissue-proved proximal cholangiocarcinoma. J Gastroenterol Hepatol. 1994; 9 134-137
191 Lesurtel M, Regimbeau J M, Farges O, Colombat M, Sauvanet A, Belghiti J. Intrahepatic cholangiocarcinoma and hepatolithiasis: an unusual association in Western countries. Eur J Gastroenterol Hepatol. 2002; 14 1025-1027
192 Lee K T, Liu T S. Expression of transforming growth factor betas and their signaling receptors in stone-containing intrahepatic bile ducts and cholangiocarcinoma. World J Surg. 2003; 27 1143-1148
193 Terada T, Ashida K, Endo K et al.. c-erbB-2 protein is expressed in hepatolithiasis and cholangiocarcinoma. Histopathology. 1998; 33 325-331
194 Liu D, Momoi H, Li L, Ishikawa Y, Fukumoto M. Microsatellite instability in thorotrast-induced human intrahepatic cholangiocarcinoma. Int J Cancer. 2002; 102 366-371
195 Sharp G B. The relationship between internally deposited alpha-particle radiation and subsite-specific liver cancer and liver cirrhosis: an analysis of published data. J Radiat Res (Tokyo). 2002; 43 371-380
196 Yamada S, Hosoda S, Tateno H, Kido C, Takahashi S. Survey of thorotrast-associated liver cancers in Japan. J Natl Cancer Inst. 1983; 70 31-35
197 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
198 Nakeeb A, Pitt H A, Sohn T A et al.. Cholangiocarcinoma: a spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg. 1996; 224 463-473 , discussion 473-5
199 de Vries J S, de Vries S, Aronson D C et al.. Choledochal cysts: age of presentation, symptoms, and late complications related to Todani's classification. J Pediatr Surg. 2002; 37 1568-1573
200 Goto N, Yasuda I, Uematsu T et al.. Intrahepatic cholangiocarcinoma arising 10 years after the excision of congenital extrahepatic biliary dilation. J Gastroenterol. 2001; 36 856-862
201 DiBisceglie A M. Malignant neoplasms of the liver. In: Schiff ER, Sorrell MF, Maddrey WC Schiff's Diseases of the Liver. 8th ed. Philadelphia; Lippincott Raven 1999: 1294
202 Saab S, Yao F. Fibrolamellar hepatocellular carcinoma: case reports and a review of the literature. Dig Dis Sci. 1996; 41 1981-1985
203 El-Serag H B, Davila J A. Is fibrolamellar carcinoma different from hepatocellular carcinoma? A US population-based study. Hepatology. 2004; 39 798-803
204 Sooklim K, Sriplung H, Piratvisuth T. Histologic subtypes of hepatocellular carcinoma in the southern Thai population. Asian Pac J Cancer Prev. 2003; 4 302-306
205 Dadke D, Jaganath P, Krishnamurthy S, Chiplunkar S. The detection of HBV antigens and HBx-transcripts in an Indian fibrolamellar carcinoma patient: a case study. Liver. 2002; 22 87-91
206 Fong Y, Kemeny N, Lawrence T S. Cancer of the liver and biliary tree. In: Devita VT, Hellman S, Rosenberg SA Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia; Lippincott Williams and Wilkins 2001: 1177-1178
207 Lee C L, Ko Y C. Survival and distribution pattern of childhood liver cancer in Taiwan. Eur J Cancer. 1998; 34 2064-2067
208 Bortolasi L, Marchiori L, Dal Dosso I, Colombari R, Nicoli N. Hepatoblastoma in adult age: a report of two cases. Hepatogastroenterology. 1996; 43 1073-1078
209 Bunin G R. Nongenetic causes of childhood cancers: evidence from international variation, time trends, and risk factor studies. Toxicol Appl Pharmacol. 2004; 199 91-103
210 Feusner J, Plaschkes J. Hepatoblastoma and low birth weight: a trend or chance observation?. Med Pediatr Oncol. 2002; 39 508-509
211 Ikeda H, Matsuyama S, Tanimura M. Association between hepatoblastoma and very low birth weight: a trend or a chance?. J Pediatr. 1997; 130 557-560
212 DiBisceglie A M. Malignant neoplasms of the liver. In: Schiff ER, Sorrell MF, Maddrey WC Schiff's Diseases of the Liver. 8th ed. Philadelphia; Lippincott Raven 1999: 1281-1304
213 Mani H, Van Thiel D H. Mesenchymal tumors of the liver. Clin Liver Dis. 2001; 5 219-257 , viii
214 Molina E, Hernandez A. Clinical manifestations of primary hepatic angiosarcoma. Dig Dis Sci. 2003; 48 677-682
215 Falk H, Herbert J, Crowley S et al.. Epidemiology of hepatic angiosarcoma in the United States: 1964-1974. Environ Health Perspect. 1981; 41 107-113
216 Hozo I, Miric D, Bojic L et al.. Liver angiosarcoma and hemangiopericytoma after occupational exposure to vinyl chloride monomer. Environ Health Perspect. 2000; 108 793-795
217 Kielhorn J, Melber C, Wahnschaffe U, Aitio A, Mangelsdorf I. Vinyl chloride: still a cause for concern. Environ Health Perspect. 2000; 108 579-588
218 Lee F I, Smith P M, Bennett B, Williams D M. Occupationally related angiosarcoma of the liver in the United Kingdom 1972-1994. Gut. 1996; 39 312-318
219 Falk H, Caldwell G G, Ishak K G, Thomas L B, Popper H. Arsenic-related hepatic angiosarcoma. Am J Ind Med. 1981; 2 43-50
220 Roat J W, Wald A, Mendelow H, Pataki K I. Hepatic angiosarcoma associated with short-term arsenic ingestion. Am J Med. 1982; 73 933-936
221 Ito Y, Kojiro M, Nakashima T, Mori T. Pathomorphologic characteristics of 102 cases of thorotrast-related hepatocellular carcinoma, cholangiocarcinoma, and hepatic angiosarcoma. Cancer. 1988; 62 1153-1162
222 Przygodzki R M, Finkelstein S D, Keohavong P et al.. Sporadic and thorotrast-induced angiosarcomas of the liver manifest frequent and multiple point mutations in K-ras-2. Lab Invest. 1997; 76 153-159
223 Falk H, Thomas L B, Popper H, Ishak K G. Hepatic angiosarcoma associated with androgenic-anabolic steroids. Lancet. 1979; 2 1120-1123
224 Rosenthal A K, Klausmeier M, Cronin M E, McLaughlin J K. Hepatic angiosarcoma occurring after cyclophosphamide therapy: case report and review of the literature. Am J Clin Oncol. 2000; 23 581-583
225 DiBisceglie A M. Malignant neoplasms of the liver. In: Schiff ER, Sorrell MF, Maddrey WC Schiff's Diseases of the Liver. 8th ed. Philadelphia; Lippincott Raven 1999: 1300
226 Ayoub J P, Hess K R, Abbruzzese M C, Lenzi R, Raber M N, Abbruzzese J L. Unknown primary tumors metastatic to liver. J Clin Oncol. 1998; 16 2105-2112
227 Kew M C. Hepatic tumors and cysts. In: Feldman M, Friedman LS, Sleisenger MH, Scharschmidt BF Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/ Management. 7th ed. Philadelphia; Saunders 2002: 1589-1590
228 Hoe A L, Royle G T, Taylor I. Breast liver metastases: incidence, diagnosis and outcome. J R Soc Med. 1991; 84 714-716
229 Gorog D, Toth A, Weltner J. Prognosis of untreated liver metastasis from rectal cancer. Acta Chir Hung. 1997; 36 106-107
230 Alexander H R, Allegra C J, Lawrence T S. Metastatic cancer to the liver. In: Devita VT, Hellman S, Rosenberg SA Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia; Lippincott Williams and Wilkins 2001: 2690
231 Ferlito A, Shaha A R, Silver C E, Rinaldo A, Mondin V. Incidence and sites of distant metastases from head and neck cancer. ORL J Otorhinolaryngol Relat Spec. 2001; 63 202-207
232 Bralet M, Regimbeau J, Pineau P et al.. Hepatocellular carcinoma occurring in nonfibrotic liver: epidemiologic and histopathologic analysis of 80 French cases. Hepatology. 2000; 32 200-204

Kia SaeianM.D. M.Sc.

Division of Gastroenterology and Hepatology, Medical College of Wisconsin

9200 W. Wisconsin Avenue, Milwaukee, WI 53226