World Journal of Surgery

, Volume 32, Issue 7, pp 1389–1395 | Cite as

Malignant Liver Tumors in South African Children: A National Audit

  • S. W. Moore
  • A. Davidson
  • G. P. Hadley
  • M. Kruger
  • J. Poole
  • D. Stones
  • L. Wainwright
  • G. Wessels



Malignant liver tumors (mostly hepatoblastoma [HB] and hepatocellular carcinoma [HCC]) are uncommon, representing 0.5%–2% of childhood malignancies worldwide. The pattern of liver tumors appears to differ in Southern Africa as a result of infectious factors (e.g., hepatitis B/retroviral disease (HIV). This study aimed to assess recent changes in the prevalence and surgical management of liver tumors in South African children.


Data were obtained from the tumor registry and pediatric oncology units in South African hospitals to audit and review the epidemiology, treatment, and outcome of malignant hepatic tumors in South African children.


Malignant primary hepatic tumors were reported in 274 children (ages 0–14 years) from 1988 through June 2006. Of these 134 (48%) had HB; 77 (27%) had HCC (9 [3%] fibrolamellar subtype); 38 (13%), vascular tumors; and 17 (6%), liver sarcomas. In a further 8 patients (3%) other tumors included lymphoma and endodermal sinus tumor. Vascular tumors included hemangioendotheliomas (12), and there were 5 malignant tumors in children with HIV, including 1 angiosarcoma and 13 Kaposi sarcoma-like tumors. Hepatoblastoma occurred at a mean age of 1.47 years, and none were encountered in patients > 4 years of age. Hepatocellular carcinoma mostly occurred in the older patients (mean age: 10.48 years), but 6% presented in patients < 8 years of age (10 months, 2, 2.6, 5, 5, and 6 years). Hepatic sarcoma occurred at a mean age of 7.66 years and had a female predominance (M:F ratio: 0.4). The relative HCC prevalence (male predominant: hepatitis B related) was reflected in the low HB:HCC (1.67) ratio. However, a significant decrease in HCC was attributed to the effect of hepatitis B inoculation. There appeared to be an increase in the incidence of vascular tumors, presumably the result of an increase in Kaposi-like sarcoma in retrovirus-positive patients. The surgical resection rate was low because most patients presented late, with advanced disease. Survival was 11% and 52% for HB and HCC, respectively, and was related to chemotherapeutic response and complete surgical resection.


Liver tumors appear to have a different epidemiological pattern in South Africa. The observed increased HCC prevalence appears to be decreasing with hepatitis B vaccination. Retroviral disease does not yet appear to have a major influence on the distribution of liver tumors in South Africa, although it possibly affects the vascular tumor prevalence.


  1. 1.
    Ishak KG, Glunz PR (1967) Hepatoblastoma and hepatocellular carcinoma in infancy and childhood: report in 47 cases. Cancer 20:396–422PubMedCrossRefGoogle Scholar
  2. 2.
    Bosch FX, Ribes J, Borras J (1999) Epidemiology of primary liver cancer. Semin Liv Dis 19:271–285CrossRefGoogle Scholar
  3. 3.
    Kew MC (2002) Epidemiology of hepatocellular carcinoma. Toxicology 181–182:35–38PubMedCrossRefGoogle Scholar
  4. 4.
    Davila JA, Petersena NJ, Nelson HA et al (2003) Geographic variation within the United States in the incidence of hepatocellular carcinoma. J Clin Epidemiol 56:487–493PubMedCrossRefGoogle Scholar
  5. 5.
    Moore SW, Millar AJW, Hadley GP et al (2004) Hepatocellular carcinoma and liver tumors in South African children: a case for increased prevalence. Cancer 101:642–649PubMedCrossRefGoogle Scholar
  6. 6.
    Jaskiewicz K, Banach L, Izycka E (1995) Hepatocellular carcinoma in young patients: histology, cellular differentiation, HBV infection and oncoprotein p53. Anticancer Res 15:2723–2725PubMedGoogle Scholar
  7. 7.
    Sloane D, Chen H, Howell C (2006) Racial disparity in primary hepatocellular carcinoma: tumor stage at presentation, surgical treatment and survival. J Natl Med Assoc 98:1934–1939PubMedGoogle Scholar
  8. 8.
    Spector LG, Feusner JH, Ross JA (2004) Hepatoblastoma and low birth weight. Pediatr Blood Cancer 43:706PubMedCrossRefGoogle Scholar
  9. 9.
    Slovis TL, Roebuck DJ (2006) Hepatoblastoma: why so many low-birth-weight infants? Pediatr Radiol 36:173–174PubMedCrossRefGoogle Scholar
  10. 10.
    Ansell P, Mitchell CD, Roman E et al (2005) Relationships between perinatal and maternal characteristics and hepatoblastoma: a report from the UKCCS. Eur J Cancer 41:741–748PubMedCrossRefGoogle Scholar
  11. 11.
    Reynolds P, Urayama KY, Von Behren J et al (2004) Birth characteristics and hepatoblastoma risk in young children. Cancer 100:1070–1076PubMedCrossRefGoogle Scholar
  12. 12.
    Feusner J, Plaschkes J (2002) Hepatoblastoma and low birth weight: a trend or chance observation? Med Pediatr Oncol 39:508–509PubMedCrossRefGoogle Scholar
  13. 13.
    McLaughlin CC, Baptiste MS, Schymura MJ et al (2006) Maternal and infant birth characteristics and hepatoblastoma. Am J Epidemiol 163:818–828PubMedCrossRefGoogle Scholar
  14. 14.
    Craig JR, Peters RL, Edmondson HA et al (1980) Fibrolamellar carcinoma of the liver. Cancer 46:372–379PubMedCrossRefGoogle Scholar
  15. 15.
    Pritchard J, Brown J, Shafford E et al (2000) Cisplatin, doxorubicin and delayed surgery for childhood hepatoblastoma: a successful approach—results of the first prospective study of the International Society of Pediatric Oncology. J Clin Oncol 18:3819–3828PubMedGoogle Scholar
  16. 16.
    Exelby P, Filler R, Grosfeld JL (1974) Liver tumors in children in the particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical survey system. J Pediatr Surg 10:329–337Google Scholar
  17. 17.
    Lanier AP, Kelly JJ, Maxwell J et al (2006) Cancer in Alaska Native people, 1969–2003. Alaska Med 48:30–59PubMedGoogle Scholar
  18. 18.
    Chen CH, Chen YY, Chen GH et al (2004) Hepatitis B virus transmission and hepatocarcinogenesis: a 9 year retrospective cohort of 13676 relatives with hepatocellular carcinoma. J Hepatol 40:653–659PubMedCrossRefGoogle Scholar
  19. 19.
    Parkin DM (2006) The global health burden of infection-associated cancers in the year 2002. Int J Cancer 118:3030–3044PubMedCrossRefGoogle Scholar
  20. 20.
    El-Serag HB, Mason AC (1999) Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 340:745–750PubMedCrossRefGoogle Scholar
  21. 21.
    Jepsen P, Vilstrup H, Tarone RE et al (2007) Incidence rates of hepatocellular carcinoma in the U.S. and Denmark: recent trends. Int J Cancer 121:1624–1626PubMedCrossRefGoogle Scholar
  22. 22.
    von Schweinitz D, Burger D, Weinel P et al (1994) Therapy of malignant liver tumors in childhood: an intermediate report of the HB–89 multicentre study of the GPOH. Med Pediatr Oncol 23:170–287Google Scholar
  23. 23.
    Davies JQ, Hall de la M, Kaschula ROC et al (2004) Hepatoblastoma— evolution of management, outcome and significance of histology of the resected tumor. A 30-year experience with 41 cases. J Pediatr Surg 39:1321–1327PubMedCrossRefGoogle Scholar
  24. 24.
    Darbari A, Sabin KM, Shapiro CN et al (2003) Epidemiology of primary hepatic malignancies in U.S. children. Hepatology 38:560–566PubMedCrossRefGoogle Scholar
  25. 25.
    Munoz N, Bosch FX (1987) Epidemiology of hepatocellular carcinoma. In: Okuda K, Ishgak K (eds) Neoplasms of the Liver, Springer-Verlag, Tokyo, pp 3–19Google Scholar
  26. 26.
    Okuda K, Okuda H (1999) Malignant tumors. In: Bircher J, Benhamou J-P, McIntyeare N et al (eds) Oxford Textbook of Clinical Hepatology, Oxford Medical Publishers, New York, pp 1491–1530Google Scholar
  27. 27.
    Stocker JT, Husain AN, Dehner LP et al (2001) The liver, gallbladder and biliary tract. In: Stocker JT, Dehner LP, (eds) Pediatric Pathology, Williams and Wilkins, Philadelphia, Lipincott, pp 705–797Google Scholar
  28. 28.
    Gauthier F, Valayer J, Le Thai B et al (1986) Hepatoblastoma and hepatocellular carcinoma in children: analysis of a series of 29 cases. J Pediatr Surg 21:424–429PubMedCrossRefGoogle Scholar
  29. 29.
    von Schweinitz D, Byeard DJ, Hecker H et al (1997) Efficiency and toxicity of ifosfamide, cisplatin and doxorubicin in the treatment of childhood hepatoblastoma. Study Committee of the Cooperative Paediatric Liver Tumor Study HB89 of the German Society for Paediatric Oncology and Haematology. Eur J Cancer 33:1243–1249CrossRefGoogle Scholar
  30. 30.
    Czausderna P, MacKinlay G, Perilongo G et al (2002) Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology Group. J Clin Oncol 20:2798–2804CrossRefGoogle Scholar
  31. 31.
    Rowland JM (2002) Hepatoblastoma: assessment of criteria for histologic classification. Med Pediatr Oncol 39:478–483PubMedCrossRefGoogle Scholar
  32. 32.
    Abeldev GI, Perova SD, Khramkova ZA et al (1963) Production of embryonal alpha-globulin by transplantable mouse hepatomas. Transplant 1:174–180CrossRefGoogle Scholar
  33. 33.
    Purves LR, MacNab M, Geddes EW et al (1968) Serum alpha foetoprotein and primary liver cancer. Lancet 1:921–922PubMedCrossRefGoogle Scholar
  34. 34.
    Kew MC (2000) Hepatocellular cancer. Clin Liver Dis 4:257–268PubMedCrossRefGoogle Scholar
  35. 35.
    Kashala LO, Kalengayi MMR, Essex M (1992) Alpha-foetoprotein synthesis in human hepatocellular carcinoma: correlation with hepatitis B surface antigen expression. Cancer Invest 10:6:513–522CrossRefGoogle Scholar
  36. 36.
    Ni YH, Chang MH, Huang LM et al (2001) Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination. Ann Intern Med 135:796–800PubMedGoogle Scholar
  37. 37.
    Stiller CA, Pritchard J, Steliarova-Foucher E (2006) Liver cancer in European children: incidence and survival, 1978–1997. Report from the Automated Childhood Cancer Information System project. Eur J Cancer 42:2115–2123PubMedCrossRefGoogle Scholar
  38. 38.
    Chang MH, Chen CJ, Lai MS et al (1997) Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. N Engl J Med 336:1855–1859PubMedCrossRefGoogle Scholar
  39. 39.
    Voigt M, Kirsch R (1995) Universal infant immunisation for hepatitis B—from dream to reality. S Afr Med J 85:339PubMedGoogle Scholar
  40. 40.
    Kew MC (1996) Progress towards the comprehensive control of hepatitis B in Africa: a view from South Africa. Gut 38:S31–S36PubMedCrossRefGoogle Scholar
  41. 41.
    Kensler TW, Egner PA, Wang JB et al (2002) Strategies for chemoprevention of liver cancer. Eur J Cancer Prev 11: S58–64PubMedGoogle Scholar
  42. 42.
    Ruymann FB, Raney RB Jr, Crist WM et al (1985) Rhabdomyosarcoma of the biliary tree in childhood. A report from the Intergroup Rhabdomyosarcoma Study. Cancer 56:575–581PubMedCrossRefGoogle Scholar
  43. 43.
    Kiani B, Ferrell LD, Qualman S et al (2006) Immunohistochemical analysis of embryonal sarcoma of the liver. Appl Immunohistochem Mol Morphol 14:193–197PubMedCrossRefGoogle Scholar
  44. 44.
    Christison-Lagay ER, Burrows PE, Alomari A et al (2007) Hepatic hemangiomas: subtype classification and development of a clinical practice algorithm and registry. J Pediatr Surg 42:62–67PubMedCrossRefGoogle Scholar
  45. 45.
    Ferrari A, Casanova M, Bisogno G et al (2002) Malignant vascular tumors in children and adolescents: a report from the Italian and German Soft Tissue Sarcoma Cooperative Group. Med Pediatr Oncol 39:109–114PubMedCrossRefGoogle Scholar
  46. 46.
    Lyons LL, North PE, Mac-Moune Lai F et al (2004) Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma. Am J Surg Pathol 28:559–568PubMedGoogle Scholar
  47. 47.
    Nazir Z, Pervez S (2006) Malignant vascular tumors of liver in neonates. J Pediatr Surg 41:e49–51PubMedCrossRefGoogle Scholar
  48. 48.
    Makhlouf HR, Ishak KG, Goodman ZD (1999) Epithelioid hemangioendothelioma of the liver: a clinicopathologic study of 137 cases. Cancer 85:562–582PubMedCrossRefGoogle Scholar
  49. 49.
    Bonnet F, Morlat P (2006) Cancer and HIV infection: any association? Rev Med Interne 27:227–235PubMedGoogle Scholar
  50. 50.
    Bower M, Mazhar D, Stebbing J (2006) Should cervical cancer be an acquired immunodeficiency syndrome-defining cancer? J Clin Oncol 24:2417–2419PubMedCrossRefGoogle Scholar
  51. 51.
    Sharif K, Ramani P, Lochbuhler H et al (2006) Recurrent mesenchymal hamartoma associated with 19q translocation. A call for more radical surgical resection. Eur J Pediatr Surg 16:64–67PubMedCrossRefGoogle Scholar
  52. 52.
    Begueret H, Trouette H, Vielh P et al (2001) Hepatic undifferentiated embryonal sarcoma: malignant evolution of mesenchymal hamartoma? Study of one case with immunohistochemical and flow cytometric emphasis. J Hepatol 34:178–179PubMedCrossRefGoogle Scholar
  53. 53.
    Bove KE, Blough RI, Soukup S (1998) Third report of t(19q)(13.4) in mesenchymal hamartoma of liver with comments on link to embryonal sarcoma. Pediatr Dev Pathol 1:438–442PubMedCrossRefGoogle Scholar
  54. 54.
    de Chadarevian JP, Pawel BR, Faerber EN et al (1994) Undifferentiated (embryonal) sarcoma arising in conjunction with mesenchymal hamartoma of the liver. Mod Pathol 7:490–493PubMedGoogle Scholar
  55. 55.
    O’Sullivan MJ, Swanson PE, Knoll J et al (2001) Undifferentiated embryonal sarcoma with unusual features arising within mesenchymal hamartoma of the liver: report of a case and review of the literature. Pediatr Dev Pathol 4:482–489PubMedCrossRefGoogle Scholar
  56. 56.
    Katzenstein HM, Krailo MD, Malogolowkin MH et al (2003) Fibrolamellar hepatocellular carcinoma in children and adolescents. Cancer 97:2006–2012PubMedCrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2008

Authors and Affiliations

  • S. W. Moore
    • 1
  • A. Davidson
    • 2
  • G. P. Hadley
    • 3
  • M. Kruger
    • 4
  • J. Poole
    • 5
  • D. Stones
    • 6
  • L. Wainwright
    • 5
  • G. Wessels
    • 7
  1. 1.Department of Pediatric SurgeryUniversity of StellenboschTygerbergSouth Africa
  2. 2.University of Cape TownRondeboschSouth Africa
  3. 3.Department of Pediatric SurgeryUniversity of Kwazulu-NatalCongellaSouth Africa
  4. 4.Department of PediatricsUniversity of PretoriaPretoriaSouth Africa
  5. 5.Department of PediatricsUniversity of the WitwatersrandJohannesburgSouth Africa
  6. 6.Department of PediatricsUniversity of the Free StateBloemfonteinSouth Africa
  7. 7.Department of PediatricsUniversity of StellenboschTygerbergSouth Africa

Personalised recommendations