Advertisement

European Radiology

, Volume 17, Issue 10, pp 2519–2530 | Cite as

Biliary and reticuloendothelial impairment in hepatocarcinogenesis: the diagnostic role of tissue-specific MR contrast media

  • Carlo Bartolozzi
  • Laura Crocetti
  • Riccardo Lencioni
  • Dania Cioni
  • Clotilde Della Pina
  • Daniela Campani
Hepatobiliary-Pancreas

Abstract

The development and progression of a hepatocellular carcinoma (HCC) in a chronically diseased liver, i.e., the carcinogenesis, comprise a multistep and long-term process. Morphologically, this process is associated with the presence of distinct nodular lesions in the liver that are called ‘preneoplastic lesions.’ These preneoplastic lesions are associated with and can precede the growth and progression of well-differentiated HCCs . The characterization of nodular lesions and demonstration of the multistep development of HCC in the cirrhotic liver by imaging modalities represent a challenging issue. The arterial hypervascular supply, depicted by different dynamic studies, represents a fundamental radiological criterion for the diagnosis of HCC in cirrhosis. Magnetic resonance (MR) imaging performed with tissue-specific contrast media can help to investigate the “grey area” of carcinogenesis, in which significant histological changes are already present without any imaging evidence of neoangiogenesis. The purpose of this review is to provide information on the properties of tissue-specific MR contrast agents and on their usefulness in the demonstration of the pathologic changes that take place at the level of the biliary and reticuloendothelial systems during the carcinogenetic process in liver cirrhosis.

Keywords

Hepatocellular carcinoma Carcinogenesis Magnetic resonance imaging Contrast media 

References

  1. 1.
    Llovet JM, Burroughs A, Bruix J (2003) Hepatocellular carcinoma. Lancet 362:1907–1917PubMedCrossRefGoogle Scholar
  2. 2.
    Russo MW, Wei JT, Thiny MT et al (2004) Digestive and liver disease statistics, 2004. Gastroenterology 126:1448–1453PubMedCrossRefGoogle Scholar
  3. 3.
    Yeh SH, Chen PJ, Shau WY et al (2001) Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma. Gastroenterology 121:699–709PubMedCrossRefGoogle Scholar
  4. 4.
    Su Q, Benner A, Hofmann WJ, Otto G, Pichlmayr R, Bannsch P (1997) Human hepatic preneoplasia: phenotypes and proliferation kinetics of foci and nodules of altered hepatocytes and their relationship to liver cell dysplasia. Virchows Archiv 431:391–406PubMedCrossRefGoogle Scholar
  5. 5.
    Borzio M, Roncalli M, Trere D, Derenzini M (1998) Preneoplastic cellular changes in liver. Hepatology 28:1435–1436PubMedCrossRefGoogle Scholar
  6. 6.
    Saeki R, Nagai H, Kaneko S et al (2000) Intratumoral genomic heterogeneity in human hepatocellular carcinoma detected by restriction landmark genomic scanning. J Hepatol 33:99–105PubMedCrossRefGoogle Scholar
  7. 7.
    Semelka RC, Helmberger TK (2001) Contrast agents for MR imaging of the liver. Radiology 278:27–38Google Scholar
  8. 8.
    MacSween RNM, Burt AD, Portmann BC, Scheuer PJ, Anthony PP (2001) Pathology of the liver, 4th edn. Churchill Livingstone, LondonGoogle Scholar
  9. 9.
    Bruix J, Sherman M, Llovet JM et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35:421–430PubMedCrossRefGoogle Scholar
  10. 10.
    Bruix J, Sherman M, Practice Guidelines Committee, American Association for the Study of Liver Diseases (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236PubMedCrossRefGoogle Scholar
  11. 11.
    Lencioni R, Cioni D, Crocetti L, Della Pina MC, Bartolozzi C (2004) Magnetic resonance imaging of liver tumors. J Hepatol 40:162–171PubMedCrossRefGoogle Scholar
  12. 12.
    Kiernan F (1833) The anatomy and physiology of the liver. Philos Trans R Sic Lond 123:711–770CrossRefGoogle Scholar
  13. 13.
    Rappaport AM, Borowy ZJ, Lough WM, Lotto WN(1954) Subdivision of heaxagonal liver lobules into a structural and functional unit. Role in hepatic physiology and pathology. Anat Rec 119:11–34PubMedCrossRefGoogle Scholar
  14. 14.
    Matsumoto T, Kawakami M (1982) The unit-concept of hepatic parenchyma-a re-examination based on angiorchitectural studies. Acta Pathol Jpn 32:285–314PubMedGoogle Scholar
  15. 15.
    Ekataksin W, Wake K (1997) New concepts in biliary and vascular anatomy of the liver. In: Boyer JL, Ockner RK (eds) Proress in liver disease, vol XV. WB Saunders, Philadelphia, pp 1–30Google Scholar
  16. 16.
    Ishak KG, Goodman ZD, Stocker JT (1999) Atlas of tumor pathology: tumors of the liver and intrahepatic bile ducts. 3rd series, fascicle 31. Armed Forces Institute of Pathology,Washington, DCGoogle Scholar
  17. 17.
    Anthony PP (1989) Liver tumors: an update. In: Anthony PP, MacSween RMM (eds) Recent advances in histopathology, no 14. Chuchill Livingstone, Edinburgh, pp 185–203Google Scholar
  18. 18.
    Tanaka M, Nakashima O, Wada Y, Kage M, Kojiro M (1996) Patomorphological study of Kupffer cells in hepatocellular carcinoma and hyperplastic nodular lesions in the liver. Hepatology 24:807–812PubMedCrossRefGoogle Scholar
  19. 19.
    Rojkind M (1988) Fibrosis and cirrhosis as alterations in homeostasis of the liver ecosystem. In: Gitnick G (ed) Principles and practice of gastroenterology and hepatology. Elsevier, New York, pp 1121–1134Google Scholar
  20. 20.
    International Working Party (1995) Terminology of nodular hepatocellular lesions. Hepatology 22:983–993Google Scholar
  21. 21.
    Roncalli M (2004) Hepatocellular nodules in cirrhosis: focus on diagnostic criteria on liver biopsy. A Western experience. Liver Transpl 10:S9–S15PubMedCrossRefGoogle Scholar
  22. 22.
    Maggioni M, Coggi G, Cassani B et al (2000) Molecular changes in hepatocellular dysplastic nodules on microdissected liver biopsies. Hepatology 32:942–946PubMedCrossRefGoogle Scholar
  23. 23.
    Sun M, Eshleman JR, Ferrell LD et al (2001) An early lesion in hepatic carcinogenesis: loss of heterozygosity in human cirrhotic livers and dysplastic nodules at the 1p36–p34 region. Hepatology 33:1415–1424PubMedCrossRefGoogle Scholar
  24. 24.
    Tornillo L, Carafa V, Sauter G et al (2002) Chromosomal alterations in hepatocellular nodules by comparative genomic hybridization: high-grade dysplastic nodules represent early stages of hepatocellular carcinoma. Lab Invest 82:547–853PubMedCrossRefGoogle Scholar
  25. 25.
    Terasaki S, Kanedo S, Kobayashi K, Nonamoura A, Nakanuma Y (1998) Histological features predicting malignant transformation of non-malignant hepatocellular nodules: a prospective study. Gastroenterology 115:1216–1222PubMedCrossRefGoogle Scholar
  26. 26.
    Theise N (1995) Macroregenerative (dysplastic) nodules and hepatocarcinogenesis: theoretical and clinical consideration. Sem Liver Dis 15:360–371CrossRefGoogle Scholar
  27. 27.
    Seki S, Sakaguchi H, Kitada T et al (2000) Outcomes of dysplastic nodules in human cirrhotic liver: a clinicopathological study. Clin Cancer Res 6:3469–3473PubMedGoogle Scholar
  28. 28.
    Borzio M, Fargion S, Borzio F et al (2003) Impact of large regenerative, low grade and high grade dysplastic nodules in hepatocellular carcinoma development. J Hepatol 39:208–214PubMedCrossRefGoogle Scholar
  29. 29.
    Kojiro M, Nakashima O (1999) Histopathologic evaluation of hepatocellular carcinoma with special reference to small early stage tumors. Semin Liver Dis 19:287–296PubMedGoogle Scholar
  30. 30.
    Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver: a study of 100 cases among 18,900 necropsies. Cancer 7:462–503PubMedCrossRefGoogle Scholar
  31. 31.
    Manifold IH, Triger P, Underwod JC (1983) Kupffer cell depletion in chronic liver disease: implications for hepatic carcinogenesis. Lancet 2:431–433PubMedCrossRefGoogle Scholar
  32. 32.
    Reimer P, Schneider G, Schima W (2004) Hepatobiliary contrast agents for contrast-enhanced MRI of the liver: properties, clinical development and applications. Eur Radiol 14:559–578PubMedCrossRefGoogle Scholar
  33. 33.
    de Haen C, Lorusso V, Tirone P (1996) Hepatic transport of gadobenate dimeglumine in TR-rats. Acad Radiol 3:S452–S454PubMedCrossRefGoogle Scholar
  34. 34.
    Kirchin MA, Pirovano GP, Spinazzi A (1998) Gadobenate dimeglumine (Gd-BOPTA). An overview. Invest Radiol 33:798–809PubMedCrossRefGoogle Scholar
  35. 35.
    Spinazzi A, Lorusso V, Pirovano G, Kirchin M (1999) Safety, tolerance, biodistribution, and MR imaging enhancement of the liver with gadobenate dimeglumine: results of clinical pharmacologic and pilot imaging studies in nonpatient and patient volunteers. Acad Radiol 6:282–291PubMedCrossRefGoogle Scholar
  36. 36.
    Spinazzi A, Lorusso V, Pirovano G, Taroni P, Kirchin M, Davies A (1998) Multihance clinical pharmacology: biodistribution and MR enhancement of the liver. Acad Radiol 5(Suppl 1):S86–S89PubMedCrossRefGoogle Scholar
  37. 37.
    Huppertz A, Balzer T, Blakeborough A et al (2004) Improved detection of focal liver lesions in MRI. A multicenter comparison of Gd-EOB-DTPA with intraoperative findings. Radiology 230:266–275PubMedCrossRefGoogle Scholar
  38. 38.
    Oudkerk M, Torres CG, Song B et al (2002) Characterization of liver lesions with mangafodipir trisodium-enhanced MR imaging: multicenter study comparing MR and dual-phase spiral CT. Radiology 223:517–524PubMedCrossRefGoogle Scholar
  39. 39.
    Petersein J, Spinazzi A, Giovagnoni A et al (2000) Focal liver lesions: evaluation of the efficacy of gadobenate dimeglumine in MR imaging. A multicenter phase III clinical study. Radiology 215:727–736PubMedGoogle Scholar
  40. 40.
    Tsuda N, Kato N, Murayama C, Narazaki M, Yokawa T (2004) Potential for differential diagnosis with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in experimental hepatic tumors. Invest Radiol 39:80–88PubMedCrossRefGoogle Scholar
  41. 41.
    Ros PR, Freeny PC, Harms SE et al (1995) Hepatic MR imaging with ferumoxide: a multicentric clinical trial of the safety and efficacy in the detection of focal hepatic lesions. Radiology 196:481–488PubMedGoogle Scholar
  42. 42.
    Reimer P, Balzer T (2003) Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications. Eur Radiol 13:1266–1276PubMedGoogle Scholar
  43. 43.
    Kopp AF, Laniado M, Dammamm F et al (1997) MR imaging of the liver with Resovist: safety, efficacy, and pharmacodynamic properties. Radiology 204:749–756PubMedGoogle Scholar
  44. 44.
    Rofsky NM, Weinreb JC, Bernardino ME, Youn SW, Lee JK, Noz ME (1993) Hepatocellular tumors: characterization with Mn-DPDP enhanced imaging. Radiology 188:53–59PubMedGoogle Scholar
  45. 45.
    Ni Y, Marchal G, Zhang X et al (1993) The uptake of manganese dipyridoxaldiphosphate by chemically induced hepatocellular carcinoma in rats: a correlation between contrast-media-enhanced magnetic resonance imaging, tumor differentiation, and vascularization. Invest Radiol 28:520–528PubMedCrossRefGoogle Scholar
  46. 46.
    Liou J, Lee JK, Borrello JA, Brown JJ (1994) Differentiation of hepatomas from nonhepatomatous masses: use of MnDPDP-enhanced MR images. Magn Reson Imaging 12:71–79PubMedCrossRefGoogle Scholar
  47. 47.
    Bartolozzi C, Donati F, Cioni D, Crocetti L, Lencioni R (2000) MnDPDP-enhanced MRI vs dual-phase spiral CT in the detection of hepatocellular carcinoma in cirrhosis. Eur Radiol 10:1697–1702PubMedCrossRefGoogle Scholar
  48. 48.
    Youk JH, Lee JM, Kim CS (2004) MRI for detection of hepatocellular carcinoma: comparison of mangafodipir trisodium and gadopentetate dimeglumine contrast agents. AJR 183:1049–1054PubMedGoogle Scholar
  49. 49.
    Murakami T, Baron RL, Peterson MS et al (1996) Hepatocellular carcinoma: MR imaging with mangafodipir trisodium (Mn-DPDP). Radiology 200:69–77PubMedGoogle Scholar
  50. 50.
    Coffin CM, Diche T, Mahfouz AE et al (1999) Benign and malignant hepatocellular tumors: evaluation of tumoral enhancement after mangafodipir trisodium injection on MR imaging. Eur Radiol 9:444–449PubMedCrossRefGoogle Scholar
  51. 51.
    Scharitzer M, Schima W, Schober et al (2005) Characterization of hepatocellular tumors: value of mangafodipir-enhanced magnetic resonance imaging. J Comput Assist Tomogr 29:181–190PubMedCrossRefGoogle Scholar
  52. 52.
    Vogl TJ, Hamm B, Schnell B et al (1993) Mn-DPDP enhancement patterns of hepatocellular lesions on MR images. J Magn Reson Imaging 3:51–58PubMedCrossRefGoogle Scholar
  53. 53.
    Hecht EM, Holland AE, Israel GM et al (2006) Hepatocellular carcinoma in the cirrhotic liver: gadolinium-enhanced 3D T1-weighted MR imaging as a stand-alone sequence for diagnosis. Radiology 239:438–447PubMedCrossRefGoogle Scholar
  54. 54.
    Pirovano G, Vanzulli A, Marti-Bonmati L et al (2000) Evaluation of the accuracy of gadobenate dimeglumine-enhanced MR imaging in the detection and characterization of focal liver lesions. AJR 175:1111–1120PubMedGoogle Scholar
  55. 55.
    Manfredi R, Maresca G, Baron R et al (1999) Delayed MR imaging of hepatocellular carcinoma enhanced by gadobenete dimeglumine (Gd-BOPTA). J Magn Reson Imaging 9:704–710PubMedCrossRefGoogle Scholar
  56. 56.
    Grazioli L, Morana G, Caudana R et al (2000) Hepatocellular carcinoma: correlation between gadobenate dimeglumine-enhanced MRI and pathologic findings. Invest Radiol 35:25–34PubMedCrossRefGoogle Scholar
  57. 57.
    Schuhmann-Giampieri G, Schmitt-Willich H, Press WR, Negishi C, Weinmann HJ, Speck U (1992) Preclinical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system. Radiology 183:59–64PubMedGoogle Scholar
  58. 58.
    Hamm B, Staks T, Mühler A et al (1995) Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging. Radiology 195:785–792PubMedGoogle Scholar
  59. 59.
    Vogl TJ, Kummel S, Hammerstingl R et al (1996) Liver tumors: comparison of MR imaging with Gd-EOB-DTPA and Gd-DTPA. Radiology 200:59–67PubMedGoogle Scholar
  60. 60.
    Reimer P, Rummeny EJ, Daldrup HE et al (1997) Enhancement characteristics of liver metastases, hepatocellular carcinomas, and hemangiomas with Gd-EOB-DTPA: preliminary results with dynamic MR imaging. Eur Radiol 7:257–280Google Scholar
  61. 61.
    Ni Y, Marchal G, Yu J, Muhler A, Lukito G, Baert AL (1994) Prolonged positive contrast enhancement with Gd-EOB-DTPA in experimental liver tumors: potential value in tissue characterization. J Magn Reson Imaging 4:355–363PubMedCrossRefGoogle Scholar
  62. 62.
    Ni Y, Marchal G (1998) Enhanced magnetic resonance imaging for tissue characterization of liver abnormalities with hepatobiliary contrast agents: an overview of preclinical animal experiments. Top Magn Reson Imaging 9:183–195PubMedCrossRefGoogle Scholar
  63. 63.
    Huppertz A, Haraida S, Kraus A et al (2005) Enhancement of focal liver lesions at gadoxetic acid-enhanced MR imaging: correlation with histopathologic findings and spiral CT-initial observations. Radiology 234:468–478PubMedCrossRefGoogle Scholar
  64. 64.
    Marchal G, Zhang X, Ni Y, Van Hecke P, Yu J, Baert AL (1993)Comparison between Gd-DTPA, Gd-EOB-DTPA, and Mn-DPDP in induced HCC in rats: a correlation study of MR imaging, microangiography, and histology. Magn Reson Imaging 11:665–674PubMedCrossRefGoogle Scholar
  65. 65.
    Vogl TJ, Hammerstingl R, Schwarz W et al (1996) Superparamagnetic iron oxide-enhanced versus gadolinium-enhanced MR imaging for differential diagnosis of focal liver lesions. Radiology 198:881–887PubMedGoogle Scholar
  66. 66.
    Imai Y, Murakami T, Yoshida S et al (2000) Superparamagnetic iron oxide-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading. Hepatology 32:205–212PubMedCrossRefGoogle Scholar
  67. 67.
    Lim JH, Choi D, Cho SK et al (2001) Conspicuity of hepatocellular nodular lesions in cirrhotic livers at ferumoxides-enhanced MR imaging: importance of Kupffer cell number. Radiology 220:669–676PubMedCrossRefGoogle Scholar
  68. 68.
    Tang Y, Yamashita Y, Arakawa A et al (1999) Detection of hepatocellular carcinoma arising in cirrhotic livers: comparison of gadolinium- and ferumoxides-enhanced MR imaging. AJR 172:1547–1554PubMedGoogle Scholar
  69. 69.
    Yamamoto H, Yamashita Y, Yoshimatsu S et al (1995) Hepatocellular carcinoma in cirrhotic livers: detection with unenhanced and iron oxide-enhanced MR imaging. Radiology 196:106–112Google Scholar
  70. 70.
    Kim SH, Choi D, Kim SH et al (2005) Ferucarbotran-enhanced MRI versus triple-phase MDCT for the preoperative detection of hepatocellular carcinoma. AJR 184:1069–1076PubMedGoogle Scholar
  71. 71.
    Pauleit D, Textor J, Bachmann R et al (2002) Hepatocellular carcinoma: detection with gadolinium- and ferumoxides-enhanced MR imaging of the liver. Radiology 222:73–80PubMedCrossRefGoogle Scholar
  72. 72.
    Kwak HS, Lee JM, Kim YK, Lee YH, Kim CS (2005) Detection of hepatocellular carcinoma: comparison of ferumoxides-enhanced and gadolinium-enhanced dynamic three-dimensional volume interpolated breath-hold MR imaging. Eur Radiol 15:140–147PubMedCrossRefGoogle Scholar
  73. 73.
    Simon G, Link TM, Wortler et al (2005) Detection of hepatocellular carcinoma: comparison of Gd-DTPA- and ferumoxides-enhanced MR imaging. Eur Radiol 15:895–903PubMedCrossRefGoogle Scholar
  74. 74.
    Clement O, Frija G, Chambon C et al (1991) Liver tumors in cirrhosis: experimental study with ferumoxides-enhanced MR imaging. Radiology 180:31–36PubMedGoogle Scholar
  75. 75.
    Kwak HS, Lee JM, Kim CS (2004) Preoperative detection of hepatocellular carcinoma: comparison of combined contrast-enhanced MR imaging and combined CT during arterial portography and CT hepatic arteriography. Eur Radiol 14:447–457PubMedCrossRefGoogle Scholar
  76. 76.
    Bhartia B, Ward J, Guthrie JA, Robinson PJ (2003) Hepatocellular carcinoma in cirrhotic livers: double-contrast thin-section MR imaging with pathologic correlation of explanted tissue. AJR 180:577–584PubMedGoogle Scholar
  77. 77.
    Lencioni R, Cioni D, Della Pina C, Crocetti L, Bartolozzi C (2005) Imaging diagnosis. Semin Liver Dis 25:162–170PubMedCrossRefGoogle Scholar
  78. 78.
    Libbrecht L, Desmet V, Roskams T (2005) Preneoplastic lesions in human carcinogenesis. Liver International 25:16–27PubMedCrossRefGoogle Scholar
  79. 79.
    Park YN, Yang CP, Fernandez GJ, Cubukcu O, Thung SN, Theise ND (1998) Neoangiogenesis and sinusoidal capillarization in dysplastic nodules of the liver. Am J Surg Pathol 22:656–662PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Carlo Bartolozzi
    • 1
  • Laura Crocetti
    • 1
  • Riccardo Lencioni
    • 1
  • Dania Cioni
    • 1
  • Clotilde Della Pina
    • 1
  • Daniela Campani
    • 2
  1. 1.Division of Diagnostic and Interventional Radiology, Department of Oncology, Transplant and Advanced Technologies in MedicineUniversity of PisaPisaItaly
  2. 2.Division of Pathology, Department of Oncology, Transplant and Advanced Technologies in MedicineUniversity of PisaPisaItaly

Personalised recommendations