The Clinical Challenge of Liver Metastasis

  • Stefano Cappato
  • Federica Brena
  • Michela Squadroni
  • Rosalba Barile
  • Davide Piccinali
  • Annalisa Mancin
  • Giorgio Quartierini
  • Orlando Goletti
  • Giordano Beretta
Chapter

Abstract

The treatment of liver metastases is generally considered as a palliative approach. A large body of literature refers to the experience gained in colorectal metastases, and surgery remains the cornerstone of treatments with a 40% survival at 5 years. Comparable results are attainable in the treatment of patients with neuroendocrine liver metastases. However, only a small proportion of these patients are suitable candidates for hepatic resection. Furthermore, there is limited data referring to the management of non-colorectal, non-neuroendocrine liver metastases, and most of the reports refer to smaller, retrospective case series with scarce information on treatment carried out during the patient’s journey. In this chapter, we present current perspectives on the management of liver metastases, with a focus on state-of-the-art resection, by drawing on clinical data provided in the medical literature.

Keywords

Liver metastases Colorectal cancer Neuroendocrine tumors 

References

  1. 1.
    Weinberg RA. The biology of cancer. New York: Garland Science; 2007.Google Scholar
  2. 2.
    Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3:453–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Kawada K, Hasegawa S, Murakami T, et al. Molecular mechanisms of liver metastasis. Int J Clin Oncol. 2011;16:464–72.CrossRefPubMedGoogle Scholar
  4. 4.
    Page AJ, Weiss MJ, Pawlik TM, et al. Surgical management of noncolorectal cancer liver metastases. Cancer. 2014;15:3111–21.CrossRefGoogle Scholar
  5. 5.
    Mueller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410:50–6.CrossRefGoogle Scholar
  6. 6.
    Wang JM, Deng X, Gong W, et al. Chemokines and their role in tumor growth and metastasis. J Immunol Methods. 1998;220:1–17.CrossRefPubMedGoogle Scholar
  7. 7.
    Spano D, Heck C, De Antonellis P, et al. Molecular networks that regulate cancer metastasis. Semin Cancer Biol. 2012;22:234–49.CrossRefPubMedGoogle Scholar
  8. 8.
    Valastyan S, Weinberg RA. Tumor metastasis: molecular insight and evolving paradigms. Cell. 2011;147:275–92.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Opinion: migrating cancer stem cells-an integrated concept of malignant tumor progression. Nat Rev Cancer. 2005;5:744–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Wicki A, Christofori G. The potential role of podoplanin in tumor invasion. Br J Cancer. 2007;96:1–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer. 2009;9:239–52.CrossRefPubMedGoogle Scholar
  12. 12.
    Gupta GP, Massaguè J. Cancer metastasis: building a framework. Cell. 2009;127:679–95.CrossRefGoogle Scholar
  13. 13.
    Auguste P, Fallavollita L, Wang N, et al. The host inflammatory response promotes liver metastasis by increasing tumor cell arrest and extravasation. Am J Pathol. 2007;170:1781–92.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Stoletov K, Kato H, Zardouzian E, et al. Visualizing extravasation dynamics of metastatic tumor cells. J Cell Sci. 2010;123:2332–41.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Erpenbeck L, Schön MP. Deadly allies: the fatal interplay between platelets and metastasizing cancer cells. Blood. 2010;115:3427–2436.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002;2(8):563–72.CrossRefPubMedGoogle Scholar
  17. 17.
    Karaosmanoglu AD, Onur MR, Ozmen NM, et al. Magnetic resonance imaging of liver metastasis. Semin Ultrasound CT MRI. 2016;37:533–48.CrossRefGoogle Scholar
  18. 18.
    Ferlay J, Shin HR, Bray F, et al. GLOBOCAN 2008, VERSION 1.2, cancer incidence and mortality worldwide. IARC CancerBase No. 10. http://globocan.iarc.fr.
  19. 19.
    Weiss L, Grundmann E, Torhost J, et al. Haematogenous metastatic patterns of colonic carcinoma : an analysis of 1541 necropsies. J Pathol. 1986;150:195–203.CrossRefPubMedGoogle Scholar
  20. 20.
    Adam R, De Gramont A, Figueras J, et al. The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus. Oncologist. 2012;17:1225–39.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Rees M, Tekkis PP, Welsh FK, et al. Evaluation of long term survival after hepatic resection for metastatic colorectal cancer. A multifactorial model of 929 patients. Ann Surg. 2008;247:125–35.CrossRefPubMedGoogle Scholar
  22. 22.
    LiverMetSurvey. International registry of patients operated for colorectal liver metastases. Available at http:// livermetsurvey.org.
  23. 23.
    Taylor A, Kanas G, Langerberg W, et al. Survival after surgical resection of hepatic metastases from colorectal cancer: a systematic review and meta-analysis. Ann Oncol. 2010;21(Suppl 8):632.Google Scholar
  24. 24.
    Scheele J, Stange R, Altendof-Hoffman A, et al. Resection of colorectal liver metastases. World J Surg. 1995;19:59–71.CrossRefPubMedGoogle Scholar
  25. 25.
    De Jong MC, Pulitano C, Ribero D, et al. Rates and pattern of recurrence following curative intent surgery for colorectal liver metastases: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250:440–8.PubMedGoogle Scholar
  26. 26.
    Fennell ML, Das IP, Clauser S, et al. The organization of multidisciplinary care teams: modeling internal and external influences on cancer care quality. J Natl Cancer Inst Monogr. 2010;2010:72–80.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230:309–18.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Mineo TC, Ambrogi V, Tonini G, et al. Long term results after resection of simultaneous and sequential lung and liver metastases from colorectal carcinoma. J Am Coll Surg. 2003;197:386–91.CrossRefPubMedGoogle Scholar
  29. 29.
    Fujita S, Akasu T, Moriya Y. Resection of synchronous liver metastases from colorectal cancer. Jpn J Clin Oncol. 2000;30:7–11.CrossRefPubMedGoogle Scholar
  30. 30.
    Capussotti L, Ferrero A, Viganò L, et al. Timing of resection of liver metastases synchronous to colorectal tumor: proposal for prognosis–based decisional model. Ann Surg Oncol. 2007;14:1143–50.CrossRefPubMedGoogle Scholar
  31. 31.
    Adam R, Bismuth H, Castaing D, et al. Repeat hepatectomy for colorectal liver metastases. Ann Surg. 1997;225:51–60.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Juez I, Rubio C, Figueras J. Multidisciplinary approach of colorectal liver metastases. Clin Transl Oncol. 2011;13:721–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Gruenberger B, Scheithauer W, Punzengruber B, et al. Importance of response to neoadjuvant chemotherapy in potentially curable colorectal cancer liver metastases. BMC Cancer. 2008;8:120.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Nordliger B, Sorbye H, Glimelius B, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013;14(12):1208–15.CrossRefGoogle Scholar
  35. 35.
    Langer B, et al. Fluorouracil plus leucovorin versus observation after potentially curative resection of liver or lung metastases from colorectal cancer (CRC): results of the ENG (EORTC/NCIC CTG/GIVo) randomized trial. Proc Am Soc Clin Oncol. 2002;21:149a.Google Scholar
  36. 36.
    Portier G, Elias D, Bouche O, et al. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol. 2006;24:4976–82.CrossRefPubMedGoogle Scholar
  37. 37.
    Primrose J, Falk S, Finch-Jones M, et al. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the new EPOC randomised controlled trial. Lancet Oncol. 2014;15:601–11.CrossRefPubMedGoogle Scholar
  38. 38.
    Adam R, Delvart V, Pascal G, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240:644–57.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Pozzo C, Basso M, Cassano A, et al. Neoadjuvant treatment of unresectable liver disease with irinotecan and 5-fluorouracil plus folinic acid in colorectal cancer patients. Ann Oncol. 2004;15:933–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Barone C, Nuzzo G, Cassano A, et al. Final analysis of colorectal cancer patients treated with irinotecan and 5-fluorouracil plus folinic acid neoadjuvant chemotherapy for unresectable liver metastases. Br J Cancer. 2007;97:1035–9.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Venook A, Niedzwiecki D, Blanke C, et al. CALGB/SWOG 80405: analysis of patients undergoing surgery as part of treatment strategy. ESMO 2014. Proffered paper session (ref LBA10).Google Scholar
  42. 42.
    Barone C, Basso M, Dadduzio V, et al. Conversion chemotherapy for technically unresectable colorectal liver metastases. Medicine. 2016;95(20):e3722.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    De Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18:2938–47.CrossRefPubMedGoogle Scholar
  44. 44.
    Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. NEJM. 2004;350:2335–42.CrossRefPubMedGoogle Scholar
  45. 45.
    Saltz LB, Clark S, Dìaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26:2013–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Huwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol. 2005;23:3502–8.CrossRefGoogle Scholar
  47. 47.
    Cunningham D, Lang I, Marcuello E, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomized phase 3 trial. Lancet Oncol. 2013;14:1077–85.CrossRefPubMedGoogle Scholar
  48. 48.
    Van Cutsem E, Köhne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. NEJM. 2009;360:1408–17.CrossRefPubMedGoogle Scholar
  49. 49.
    Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28(31):4697–705.CrossRefPubMedGoogle Scholar
  50. 50.
    Strosberg JR, Cheema A, Kvols LK, et al. A review of systemic and liver-directed therapies for metastatic neuroendocrine tumors of the gastroenteropancreatic tract. Cancer Control. 2011;18(2):127–37.CrossRefPubMedGoogle Scholar
  51. 51.
    Strosberg JR, Kvols L. Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors. World J Gastroenterol. 2010;16:2963–70.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Frilling A, Sotiropoulos GC, Li J, et al. Multimodal management of neuroendocrine liver metastases. HPB. 2010;12:361–79.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Ramage J, Davies A, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine tumors (NETs). Gut. 2012;61:6–32.CrossRefPubMedGoogle Scholar
  54. 54.
    Gu P, Wu J, Newman E, et al. Treatment of liver metastases in patients with neuroendocrine tumors of gastroesophageal and pancreatic origin. Int J Hepatol. 2012;2012:1.CrossRefGoogle Scholar
  55. 55.
    Lee E, Pachter HL, Sarpel U. Hepatic arterial embolization for the treatment of metastatic neuroendocrine neoplasms. Int J Hepatol. 2012;2012:471203.Google Scholar
  56. 56.
    Schurr PG, Strate T, Rese K, et al. Aggressive surgery improves long term survival in neuroendocrine pancreatic tumors. Ann Surg. 2007;245:273–81.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Steinmuller T, Kianmanesh R, Falconi M, et al. Consensus guidelines for the management of patients with liver metastases from digestive neuroendocrine tumors: foregut, midgut, hindgut and unknown primary. Neuroendocrinology. 2007;87:47–62.CrossRefPubMedGoogle Scholar
  58. 58.
    Harring T, Nguyen N, Gross JA, et al. Treatment of liver metastases in patients with neuroendocrine tumors: a comprehensive review. Int J Hepatol. 2011;2011:154541. 11 pagesCrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Neri F, Ercolani G, Di Gioia P, et al. Updat Surg. 2015;67:223–33.CrossRefGoogle Scholar
  60. 60.
    Rehders A, Peiper M, Stoeklein NH, et al. Hepatic metastasectomy for soft tissue sarcomas: is it justified? World J Surg. 2009;33:111–7.CrossRefPubMedGoogle Scholar
  61. 61.
    Turley RS, Peng PD, Reddy SK, et al. Hepatic resection for metastatic gastrointestinal stromal tumors in the tyrosine kinase inhibitor era. Cancer. 2012;118:3571–8.CrossRefPubMedGoogle Scholar
  62. 62.
    Zhu J, Yang Y, Zhou L, et al. A long term follow up of the imatinib mesylate treatment for the patients with recurrent gastrointestinal stromal tumors (GIST): the liver metastasis and the outcome. BMC Cancer. 2010;10:199.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Vassos N, Agaimy A, Hohenberger W, et al. Management of liver metastases of gastrointestinal stromal tumors (GIST). Ann Hepatol. 2015;14:531–9.PubMedGoogle Scholar
  64. 64.
    Seesing MFJ, Tielen R, van Hillegersberg R, van Coevorden F, de Jong KP, Nagtegaale ID, Verhoeff C, de Wilt JHW, Dutch Liver Surgery Working Group. Eur J Surg Oncol. 2016;42:1407.CrossRefPubMedGoogle Scholar
  65. 65.
    Radkani P, Ghersi MN, Paramo JC, et al. A multidisciplinary approach for the treatment of GIST liver metastasis. World J Surg Oncol. 2008;6:46.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Adam R, Chiche L, Aloia T, et al. Hepatic resection for noncolorectal non neuroendocrine liver metastases: analysis of 1452 patients and development of a prognostic model. Ann Surg. 2006;244:524–35.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Earle SA, Perez EA, Gutierrez JC, et al. Hepatectomy enables prolonged survival in selected patients with isolated noncolorectal liver metastases. J Am Coll Surg. 2006;203:436–46.CrossRefPubMedGoogle Scholar
  68. 68.
    Schmelzie M, Eisenberg CF, Matthaei M, et al. Non-colorectal, non-neuroendocrine, and non-sarcoma metastases of the liver: resection as a promising tool in the palliative management. Langenbeck’s Arch Surg. 2010;395:227–34.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Stefano Cappato
    • 1
  • Federica Brena
    • 2
  • Michela Squadroni
    • 2
  • Rosalba Barile
    • 2
  • Davide Piccinali
    • 1
  • Annalisa Mancin
    • 1
  • Giorgio Quartierini
    • 1
  • Orlando Goletti
    • 1
  • Giordano Beretta
    • 2
  1. 1.Department of General, Microinvasive and Oncological SurgeryHumanitas GavazzeniBergamoItaly
  2. 2.Department of OncologyHumanitas GavazzeniBergamoItaly

Personalised recommendations