Skip to main content

Advertisement

SpringerLink
Log in

Meeting the biologic challenge of colorectal metastases

  • Research Paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

An overview of colorectal cancer discussed (Philip Paty) the good outcome after primary management with local control in 90–95 % of colon and 85 % in rectal cancer patients with major progression to metastases and to death related to hematogenous dissemination. The major disease pathways include the APC, aneuploid pathway involving mutations of P53, KRAS, SMAD 4, or the CMP/MSI pathway, mismatched repair defect as characterized by Lynch syndrome, the major hereditary form which may also have KRAS and P53 mutations. The common sporadic colorectal cancers are MS1 high, with many patients having BRAF and KRAS mutations. The sentinel node biopsy in colorectal cancer surgery may provide more definitive staging and perhaps modification of the extent of resection with better outcome as suggested by Dr. Saha. The identification of sentinel lymph nodes outside of the planned bowel resection may increase the resection biologically indicated by the sentinel lymph node location leading to better outcome. In a small study by Dr. Saha, the operation was enhanced in 21 % by extending the length of bowel resection, which increased node recovery to 18.5 nodes versus 12 nodes with the more conventional resection, increasing nodal recovery, and positivity to 60 % with reduction to five year recurrence rate to 9 % versus 27 % with the conventional resection. A new (Swiss) technique for pathologic node examination, the OSNA (the One Step Nucleic Acid diagnostic system), was presented which demonstrated increased detection of micro-metastases in a focused pathology study of 22 patients (Zuber) to 11 out of 15 patients versus the 7 micro-metastases identified by the standard single slide per node, and compared to 14 out of 15 with an intensive multi-slide technique. This suggests value in pursuing OSNA study by other centers with relevant clinical trials to establish its true value. An analysis of liver resection for metastatic colorectal cancer (CRC) emphasized the value of 10-year follow-up (DeAngelica). The 10-year survival of 102 patients among 612 patients was 17 % (Memorial Sloan Kettering data). At the five-year point 99 of 102 survivors were NED and 86 have been free of disease since the resection. The usual five-year figure after hepatic resection reveals that one-third of five-year survivors die from recurrence of distant disease suggesting the value of longer term follow-up in these patients. An additional question reviewed related to the role of neoadjuvant systemic chemotherapy (with response rates in the 50 % range) to produce down staging of the hepatic metastases and allow one to retrieve these patients with possible residual disease. In a series of 116 patients who had hepatic resection of CRC metastases in presence of regional node metastases, post neoadjuvant chemotherapy (normally not candidates for resection) these patients were demonstrated to have a 95 % recurrence at median time of 9 months. This raises a cautionary note to the literature report of five-year survivals in the 20–30 % range for hepatic metastases in presence of extra hepatic disease. Such may reflect patient selection rather than a true measure of the biology of disease, and warrant clinical trial evaluation. Lastly, regional therapy and overall systemic therapy were addressed by Dr. Kemeny. The CALGB study of hepatic artery infusion (HAI) with FUDR, dexamethasone versus 5FU leucovorin showed an overall survival of 24.4 months with HAI versus 20 months with systemic therapy (P = 0.0034). An adjuvant trial of HAI at MSK in 156 patients showed an overall survival benefit at 2 year and recent long term 10yr follow-up showing a significant overall survival of 41 % with HAI versus 27 % with systemic therapy (5FU leucovorin). In the neoadjuvant Nordlinger trial for hepatic metastases, there was a significant outcome differences—the preoperative therapy group had 9.2 % increase of progression free survival versus the surgery alone group which suggests the value of combining neoadjuvant surgery in good risk liver resection candidates. Conclude the final lesson from this well presented mini symposium confirms the need for continued evaluation of the numerous discussion points by clinical trial.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Riles, LAG, Melbert D, Krapcho M et al (2010) SEER Cancer Statistics Review, 1975–2005. National Cancer Institute, Bethesda MD, based on November 2007 SEER data submission. Ann Surg Oncol 17:492

    Google Scholar 

  2. Nordlinger B, Rougier P (2002) Liver metastases from colorectal cancer: the turning point. J Clin Oncol 20:1442–1445

    PubMed  Google Scholar 

  3. Chua TC et al (2010) Systematic review of randomized and non randomized trials of the clinical response and outcomes of neoadjuvant systemic chemotherapy for resectable colorectal liver metastases. Ann Surg Oncol 17:492–501

    Article  PubMed  Google Scholar 

  4. Andre T et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350:2343–2351

    Article  PubMed  CAS  Google Scholar 

  5. Douillard JY et al (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer. A multicoated randomized trial. Lancet 355:1041–1047

    Article  PubMed  CAS  Google Scholar 

  6. Goldberg RM et al (2004) A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22:23–30

    Article  PubMed  CAS  Google Scholar 

  7. Bokemeyer C et al (2009) Fluorouracil, leucovorin and oxaliplatin with and without Cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27:663–671

    Article  PubMed  CAS  Google Scholar 

  8. Hurwitz H et al (2004) Bevacizumab in combination with Oxaliplatin-cancer. A randomized phase III study. J Clin Oncol 350:2335–2342

    CAS  Google Scholar 

  9. Saltz LB et al (2008) Bevacizumab in combination with Oxaliplatin based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019

    Article  PubMed  CAS  Google Scholar 

  10. Wanebo H, Berz D (2010) Neoadjuvant therapy of colorectal hepatic metastases and the role of biologic sensitizing and resistance factors. J Surg Oncol 102:891–897

    Article  PubMed  CAS  Google Scholar 

  11. Adam R et al (2001) Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. Ann Surg Oncol 8:347–353

    Article  PubMed  CAS  Google Scholar 

  12. Adam R et al (2004) Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg 240:1052–1061; discussion 1061–1064

    Google Scholar 

  13. Nordlinger B et al (2008) Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomized controlled trial. Lancet 371:1007–1016

    Article  PubMed  CAS  Google Scholar 

  14. Adam R et al (2008) Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: myth or reality? J Clin Oncol 26:1635–1641

    Article  PubMed  Google Scholar 

  15. Gruenberger B et al (2008) Importance of response to neoadjuvant chemotherapy in potentially curable colorectal cancer liver metastases. BMC Cancer 8:120

    Article  PubMed  CAS  Google Scholar 

  16. Blazer DG III et al (2008) Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol 26:5344–5351

    Article  PubMed  Google Scholar 

  17. Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–286

    Article  PubMed  CAS  Google Scholar 

  18. Olsson AK et al (2006) VEGF receptor signaling—in control of vascular function. Nat Rev Mol Cell Biol 7:359–371

    Article  PubMed  CAS  Google Scholar 

  19. Hurwitz HI et al (2005) Bevacizumab in combination with fluorouracil and leucovorin: an active regiment for first line metastatic colorectal cancer. J Clin Oncol 23:3502–3508

    Article  PubMed  CAS  Google Scholar 

  20. Van Cutsem E et al (2009) Safety and efficacy of first-line Bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer. The BEAT study. Ann Oncol 20:1842–1847

    Article  PubMed  Google Scholar 

  21. Tol J, Punt CJ (2010) Monoclonal antibodies in the treatment of metastatic colorectal cancer: a review. Clin Ther 32:437–453

    Article  PubMed  CAS  Google Scholar 

  22. Cunningham D et al (2004) Cetuximab monotherapy and Cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345

    Article  PubMed  CAS  Google Scholar 

  23. Van Cutsem E, Lang I, D’haens G et al (2008) KRAS stats on efficacy in the first-line treatment of patient with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without Cetuximab: the CRYSTAL experience. J Clin Oncol 26:abstr. 2

  24. Van Cutsem E et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408–1417

    Article  PubMed  Google Scholar 

  25. Bardelli A, Siena S (2010) Molecular mechanisms of resistance in Cetuximab and panitumumab in colorectal cancer. J Clin Oncol 28:1254–1261

    Article  PubMed  CAS  Google Scholar 

  26. Sartore-Bianchi A et al (2009) P1K3CA mutations in colorectal cancer are associated with clinical resistance to EGFR targeted monoclonal antibodies. Cancer Res 69:1851–1857

    Article  PubMed  CAS  Google Scholar 

  27. Laurent-Puig P et al (2009) Analysis of PTEN, BRAF, and EGFR status in determining benefit from Cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol 27:5924–5930

    Article  PubMed  CAS  Google Scholar 

  28. Khambata-Ford S et al (2007) Expression of epiregulin and amphineegulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with Cetuximab. J Clin Oncol 25:3230–3237

    Article  PubMed  CAS  Google Scholar 

  29. LeGolvan MP, Resnick M (2010) Pathobiology of colorectal hepatic metastases with an emphasis on prognostic factors. JSO 102:898–908

    Article  Google Scholar 

  30. Geiger TR, Peeper DS (2009) Metastasis mechanisms. Biochim Biophys Acta 1796:293–308

    PubMed  CAS  Google Scholar 

  31. Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial–mesenchymal transitions in development and disease. Cell 139:871–890

    Article  PubMed  CAS  Google Scholar 

  32. Jechlinger M, Grunert S, Tamir IH et al (2003) Expression profiling of epithelial plasticity in tumor progression. Oncogene 22:7155–7169

    Article  PubMed  CAS  Google Scholar 

  33. Spaderna S, Schmalhofer O, Hlubek F et al (2006) A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology 131:830–840

    Article  PubMed  CAS  Google Scholar 

  34. Lohi J (2001) Laminin-5 in the progression of carcinomas. J Int Cancer 94:763–767

    Article  CAS  Google Scholar 

  35. Sordat I, Rousselle P, Chaubert P et al (2000) Tumor cell budding and laminin-5 expression in colorectal carcinoma can be modulated by the tissue micro-environment. Int J Cancer 88:708–717

    Article  PubMed  CAS  Google Scholar 

  36. Guess CM, Quaranta V (2009) Defining the role of laminin-332 in carcinoma. Matrix Biol 28:445–455

    Article  PubMed  CAS  Google Scholar 

  37. Miyazaki K (2006) Laminin-5 (laminin-332): unique biological activity and role in tumor growth and invasion. Cancer Sci 97:91–98

    Article  PubMed  CAS  Google Scholar 

  38. Paschos KA, Canovas D, Bird NC (2010) The engagement of selectins and their ligands in colorectal cancer liver metastases. J Cell Mol Med 14:165–174

    Article  PubMed  CAS  Google Scholar 

  39. Paschos KA, Canovas D, Bird NC (2009) The role of cell adhesion molecules in the progression of colorectal cancer and the development of liver metastasis. Cell Signal 21:665–674

    Article  PubMed  CAS  Google Scholar 

  40. Dorudi S, Hanby AM, Poulsom R et al (1995) Level of expression of E-cadherin mRNA in colorectal cancer correlates with clinical outcome. Br J Cancer 71:614–616

    Article  PubMed  CAS  Google Scholar 

  41. Delektorskaya VV, Perevoshchikov AG, Golovkov DA, Kushlinskii NE (2005) Expression of E-cadherin, beta-catenin, and CD-44v6 cell adhesion molecules in primary tumors and metastases of colorectal adenocarcinoma. Bull Exp Biol Med 139:706–710

    Article  PubMed  CAS  Google Scholar 

  42. Han SA, Chun H, Park CM et al (2006) Prognostic significance of beta-catenin in colorectal cancer with liver metastasis. Clin Oncol 18:761–767

    Article  CAS  Google Scholar 

  43. Suzuki H, Masuda N, Shimura T et al (2008) Nuclear beta-catenin expression at the invasive front and in the vessels predicts liver metastasis in colorectal carcinoma. Anticancer Res 28:1821–1830

    PubMed  Google Scholar 

  44. Choi HN, Kim KR, Lee JH et al (2009) Serum response factor enhances liver metastasis of colorectal carcinoma via alteration of the E-cadherin/beta–catenin complex. Oncol Rep 21:57–63

    PubMed  CAS  Google Scholar 

  45. Barczyk M, Carracedo S, Gullberg D (2010) Integrins. Cell Tissue Res 339:269–280

    Article  PubMed  CAS  Google Scholar 

  46. Robertson JH, Iga AM, Sales KM et al (2008) Integrins: a method of early intervention in the treatment of colorectal liver metastases. Curr Pharm Des 14:296–305

    Article  PubMed  CAS  Google Scholar 

  47. Koretz K, Schlag P, Boumsell L, Möller P (1991) Expression of VLA-alpha 2, VLA-alpha 6, and VLA-beta 1 chains in normal mucosa and adenomas of the colon, and in colon carcinomas and their liver metastases. Am J Pathol 138:741–750

    PubMed  CAS  Google Scholar 

  48. Gong J, Wang D, Sun L et al (1997) Role of alpha 5 beta 1 integrin in determining malignant properties of colon carcinoma cells. Cell Growth Differ 8:83–90

    PubMed  CAS  Google Scholar 

  49. Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839

    Article  PubMed  CAS  Google Scholar 

  50. Zucker S, Vacirca J (2004) Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev 23:101–117

    Article  PubMed  CAS  Google Scholar 

  51. Pesta M, Holubec L, Topolcan O et al (2005) Quantitative estimation of matrix metalloproteinases 2 and 7 (MMP-2, MMP-7) and tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1, TIMP-2) in colorectal carcinoma tissue samples. Anticancer Res 25:3387–3391

    PubMed  CAS  Google Scholar 

  52. Stein U, Schlag PM (2007) Clinical, biological, and molecular aspects of metastasis in colorectal cancer. Recent Results Cancer Res 176:61–80

    Article  PubMed  CAS  Google Scholar 

  53. Rudmik LR, Magliocco AM (2005) Molecular mechanisms of hepatic metastasis in colorectal cancer. J Surg Oncol 92:347–359

    Article  PubMed  CAS  Google Scholar 

  54. Delektorskaya VV, Perevoshchikov AG, Golovkov DA, Kushlinskii NE (2007) Prognostic significance of expression of matrix metalloproteinase in colorectal adenocarcinomas and their metastases. Bull Exp Biol Med 143:455–458

    Article  PubMed  CAS  Google Scholar 

  55. Golovkov DA (2009) Key enzymes of the extracellular matrix in colorectal cancer. Bull Exp Biol Med 147:353–356

    Article  PubMed  CAS  Google Scholar 

  56. Gentner B, Wein A, Croner RS et al (2009) Differences in the gene expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in primary colorectal tumors and their synchronous liver metastases. Anticancer Res 29:67–74

    PubMed  CAS  Google Scholar 

  57. Illemann M, Bird N, Majeed A et al (2009) Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases. Int J Cancer 124:1860–1870

    Article  PubMed  CAS  Google Scholar 

  58. Friedmann Y, Vlodavsky I, Aingorn H et al (2000) Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis. Am J Pathol 157:1167–1175

    Article  PubMed  CAS  Google Scholar 

  59. Di Renzo MF, Olivero M, Giacomini A et al (1995) Overexpression and amplification of the met/HGF receptor gene during the progression of colorectal cancer. Clinical Cancer Res 1:147–154

    Google Scholar 

  60. Herynk MH, Tsan R, Radinsky R, Gallick GE (2003) Activation of c-Met in colorectal carcinoma cells leads to constitutive association of tyrosine-phosphorylated beta-catenin. Clin Exp Metastasis 20:291–300

    Article  PubMed  CAS  Google Scholar 

  61. Stein U, Walther W, Arlt F et al (2009) MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis. Nat Med 15:59–67

    Article  PubMed  CAS  Google Scholar 

  62. Siena S, Sartore-Bianchi A, Di Nicolantonio F et al (2009) Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst 101:1308–1324

    Article  PubMed  CAS  Google Scholar 

  63. Yamada M, Ichikawa Y, Yamagishi S et al (2008) Amphiregulin is a promising prognostic marker for liver metastases of colorectal cancer. Clinical Cancer Res 14:2351–2356

    Article  CAS  Google Scholar 

  64. Sullivan LA, Brekken RA (2010) The VEGF family in cancer and antibody-based strategies for their inhibition. MAbs 2:165–175

    Article  PubMed  Google Scholar 

  65. Berney CR, Yang JL, Fisher RJ et al (1998) Vascular endothelial growth factor expression is reduced in liver metastasis from colorectal cancer and correlates with urokinase-type plasminogen activator. Anticancer Res 18:973–977

    PubMed  CAS  Google Scholar 

  66. Maeda K, Nishiguchi Y, Yashiro M et al (2000) Expression of vascular endothelial growth factor and thrombospondin-1 in colorectal carcinoma. Int J Mol Med 5:373–378

    PubMed  CAS  Google Scholar 

  67. Thomas M, Augustin H (2009) The role of the angiopoietins in vascular morphogenesis. Angiogenesis 12:125–137

    Article  PubMed  CAS  Google Scholar 

  68. Ahmad SA, Liu W, Jung YD et al (2001) Differential expression of angiopoietin-1 and angiopoietin-2 in colon carcinoma. A possible mechanism for the initiation of angiogenesis. Cancer 92:1138–1143

    Article  PubMed  CAS  Google Scholar 

  69. Chung YC, Hou YC, Chang CN, Hseu TH (2006) Expression and prognostic significance of angiopoietin in colorectal carcinoma. J Surg Oncol 94:631–638

    Article  PubMed  CAS  Google Scholar 

  70. Markowitz SD, Bertagnolli MM (2009) Molecular origins of cancer: molecular basis of colorectal cancer. New Engl J Med 361:2449–2460

    Article  PubMed  CAS  Google Scholar 

  71. Kastrinakis W, Ramchurren N, Rieger K et al (1995) Increased incidence of p53 mutations is associated with hepatic metastasis in colorectal neoplastic progression. Oncogene 11:647–652

    PubMed  CAS  Google Scholar 

  72. Heide I, Thiede C, Sonntag T et al (1997) The status of p53 in the metastatic progression of colorectal cancer. Eur J Cancer 33:1314–1322

    Article  PubMed  CAS  Google Scholar 

  73. Peller S, Halevy A, Slutzki S et al (1995) p53 mutations in matched primary and metastatic human tumors. Mol Carcinog 13:166–172

    Article  PubMed  CAS  Google Scholar 

  74. de Jong KP, Gouw AS, Peeters PM et al (2005) P53 mutation analysis of colorectal liver metastases: relation to actual survival, angiogenic status, and p53 overexpression. Clin Cancer Res 11:4067–4073

    Article  PubMed  Google Scholar 

  75. Sah NK, Khan Z, Khan GJ, Bisen PS (2006) Structural, functional and therapeutic biology of survivin. Cancer Lett 244:164–171

    Article  PubMed  CAS  Google Scholar 

  76. Fang Y, Lu Z, Wang G et al (2009) Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer. Int J Colorectal Dis 24:875–884

    Article  PubMed  CAS  Google Scholar 

  77. Viehl CT, Guller U, Cecini R, Langer I, Ochsner A, Terracciano L, Riehle HM, Laffer U, Oertli D, Zuber M (2011) Sentinel lymph node procedure leads to upstaging of patients with resectable colon cancer. Results of the Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer. Ann Surg Oncol 2011; published online 10 February 2012. doi:10.1245/s10434-012-2233-6

  78. Notomi T, Okayama H, Masubuchi H et al (2000) Loop-mediated isothermal amplification of DNA. Nucleic Acids Res 105:215–222

    Google Scholar 

  79. Tsujimoto M, Nakabayashi K, Yoshidome K et al (2007) One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res 13:4807–4816

    Article  PubMed  CAS  Google Scholar 

  80. Osako T, Iwase T, Kimura K et al (2011) Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer: a comparative analysis between one-step nucleic acid amplification whole node assay and routine frozen section histology. Cancer 117:4365–4374

    Article  PubMed  CAS  Google Scholar 

  81. Tamaki Y, Akiyama F, Iwase T et al (2009) Molecular detection of lymph node metastases in breast cancer patients: results of a multicenter trial using the one-step nucleic acid amplification assay. Clin Cancer Res 15:2879–2884

    Article  PubMed  CAS  Google Scholar 

  82. Croner RS, Schellerer V, Demund H et al (2010) One step nucleic acid amplification (OSNA)—a new method for lymph node staging in colorectal carcinomas. J Transl Med 8:83

    Article  PubMed  CAS  Google Scholar 

  83. Yamamoto H, Sekimoto M, Oya M et al (2011) OSNA-based novel molecular testing for lymph node metastases in colorectal cancer patients: results from a multicenter clinical performance study in Japan. Ann Surg Oncol 18:1891–1898

    Article  PubMed  Google Scholar 

  84. Guller U, Zettl A, Worni M, Langer I, Cabalzar-Wondberg D, Viehl CT, Demartines N, Zuber M (2012) Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging? Cancer; accepted for publication

  85. Rocha FG, D’Angelica M (2010) Treatment of liver colorectal metastases: role of laparoscopy, radiofrequency ablation, and microwave coagulation. J Surg Oncol 102(8):968–974

    Article  PubMed  Google Scholar 

  86. Scheele J, Stangl R, Altendorf-Hofmann A (1990) Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg 77(11):1241–1246

    Article  PubMed  CAS  Google Scholar 

  87. Simmonds PC, Primrose JN, Colquitt JL, Garden OJ, Poston GJ, Rees M (2006) Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. Br J Cancer 94(7):982–999

    Article  PubMed  CAS  Google Scholar 

  88. Silen W (1989) Hepatic resection for metastases from colorectal carcinoma is of dubious value. Arch Surg 124(9):1021–1022

    Article  PubMed  CAS  Google Scholar 

  89. Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH, D’Angelica M (2007) Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol 25(29):4575–4580

    Article  PubMed  Google Scholar 

  90. Catenacci DV, Kozloff M, Kindler HL, Polite B (2011) Personalized colon cancer care in 2010. Semin Oncol 38(2):284–308

    Article  PubMed  CAS  Google Scholar 

  91. Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH (1999) Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 230(3):309–318

    Article  PubMed  CAS  Google Scholar 

  92. House MG, Ito H, Gönen M, Fong Y, Allen PJ, DeMatteo RP, Brennan MF, Blumgart LH, Jarnagin WR, D’Angelica MI (2010) Survival after hepatic resection for metastatic colorectal cancer: trends in outcomes for 1,600 patients during two decades at a single institution. J Am Coll Surg 210(5):744–752, 752–755

    Google Scholar 

  93. Gold JS, Are C, Kornprat P, Jarnagin WR, Gönen M, Fong Y, DeMatteo RP, Blumgart LH, D’Angelica M (2008) Increased use of parenchymal-sparing surgery for bilateral liver metastases from colorectal cancer is associated with improved mortality without change in oncologic outcome: trends in treatment over time in 440 patients. Ann Surg 247(1):109–117

    Article  PubMed  Google Scholar 

  94. Brouquet A, Abdalla EK, Kopetz S, Garrett CR, Overman MJ, Eng C, Andreou A, Loyer EM, Madoff DC, Curley SA, Vauthey JN (2011) High survival rate after two-stage resection of advanced colorectal liver metastases: response-based selection and complete resection define outcome. J Clin Oncol 29(8):1083–1090

    Article  PubMed  Google Scholar 

  95. Ekberg H, Tranberg KG, Andersson R, Lundstedt C, Hägerstrand I, Ranstam J, Bengmark S (1986) Determinants of survival in liver resection for colorectal secondaries. Br J Surg 73(9):727–731

    Article  PubMed  CAS  Google Scholar 

  96. Elias D, Liberale G, Vernerey D, Pocard M, Ducreux M, Boige V, Malka D, Pignon JP, Lasser P (2005) Hepatic and extrahepatic colorectal metastases: when resectable, their localization does not matter, but their total number has a prognostic effect. Ann Surg Oncol 12(11):900–909

    Article  PubMed  Google Scholar 

  97. Carpizo DR, Are C, Jarnagin W, Dematteo R, Fong Y, Gönen M, Blumgart L, D’Angelica M (2009) Liver resection for metastatic colorectal cancer in patients with concurrent extrahepatic disease: results in 127 patients treated at a single center. Ann Surg Oncol 16(8):2138–2146

    Article  PubMed  Google Scholar 

  98. Adam R, Pascal G, Castaing D, Azoulay D, Delvart V, Paule B, Levi F, Bismuth H (2004) Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg 240(6):1052–1061

    Google Scholar 

  99. Pawlik TM, Abdalla EK, Ellis LM, Vauthey JN, Curley SA (2006) Debunking dogma: surgery for four or more colorectal liver metastases is justified. J Gastrointest Surg 10(2):240–248

    Article  PubMed  Google Scholar 

  100. Kornprat P, Jarnagin WR, Gonen M, DeMatteo RP, Fong Y, Blumgart LH, D’Angelica M (2007) Outcome after hepatectomy for multiple (four or more) colorectal metastases in the era of effective chemotherapy. Ann Surg Oncol 14(3):1151–1160

    Article  PubMed  Google Scholar 

  101. Pawlik TM, Scoggins CR, Zorzi D, Abdalla EK, Andres A, Eng C, Curley SA, Loyer EM, Muratore A, Mentha G, Capussotti L, Vauthey JN (2005) Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg 241(5):715–722

    Article  PubMed  Google Scholar 

  102. Are C, Gonen M, Zazzali K, Dematteo RP, Jarnagin WR, Fong Y, Blumgart LH, D’Angelica M (2007) The impact of margins on outcome after hepatic resection for colorectal metastasis. Ann Surg 246(2):295–300

    Article  PubMed  Google Scholar 

  103. American Cancer Society (2011) Cancer facts & figures 2011. American Cancer Society, Atlanta

  104. Kemeny, N.E., Kemeny, M. M., Lawrence, T.S., Liver Metastases, in Clinical Oncology, M.D. Abeloff, Armitage, J., Niederhuber, J., Kastan, M., McKenna, W.G., Editor. 2004, Elsevier: Philadelphia

  105. Weiss L, Grandmann E, Torhost J et al (1986) Hematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J Pathol 150:195–203

    Article  PubMed  CAS  Google Scholar 

  106. Weiss L (1989) Metastatic inefficiency and regional therapy for liver metastases from colorectal carcinoma. Regul Cancer Treat 2:77–81

    Google Scholar 

  107. Breedis C, Young G (1954) The blood supply of neoplasms in the liver. Am J Pathol 30(5):969–977

    PubMed  CAS  Google Scholar 

  108. Ackerman NB (1974) The blood supply of experimental liver metastases. IV. Changes in vascularity with increasing tumor growth. Surgery 75(4):589–596

    Google Scholar 

  109. Sigurdson ER et al (1987) Tumor and liver drug uptake following hepatic artery and portal vein infusion. J Clin Oncol 5(11):1836–1840

    PubMed  CAS  Google Scholar 

  110. Ensminger WD (2002) Intrahepatic arterial infusion of chemotherapy: pharmacologic principles. Semin Oncol 29(2):119–125

    Article  PubMed  CAS  Google Scholar 

  111. Ensminger WD, Gyves JW (1983) Clinical pharmacology of hepatic arterial chemotherapy. Semin Oncol 10(2):176–182

    PubMed  CAS  Google Scholar 

  112. McCollins JM (1984) Pharmacologic rationale for regional drug delivery. J Clin Oncol 2(5):498–504

    Google Scholar 

  113. Collins JM (1986) Pharmacologic rationale for hepatic arterial therapy. Recent Results Cancer Res 100:140–147

    Article  PubMed  CAS  Google Scholar 

  114. Rodic R, Gomez-Abuin G, Rougier P et al (2004) Pharmacokinetic advantage of intra-arterial hepatic oxaliplatin administration: comparative results with cisplatin using a rabbit VX2 tumor model. Anticancer Drugs 15:647–650

    Article  Google Scholar 

  115. Ducreux M, Ychou M, Laplanche A et al (2005) Hepatic arterial oxaliplatin infusion plus intravenous chemotherapy in colorectal cancer with inoperable hepatic metastases: a trial of the gastrointestinal group of the Federation Nationale des Centres de Lutte Contre le Cancer. J Clin Oncol 23:4881–4887

    Article  PubMed  CAS  Google Scholar 

  116. Van Riel JMGH, Van Groeningen C, Kedde M et al (2004) Continuous administration of irinotecan by hepatic arterial infusion: a phase I and pharmacokinetic study. Clin Cancer Res 8:405–412

    Google Scholar 

  117. Tandon R, Bunnell I, Copper R (1973) The treatment of metastatic carcinoma of the liver by percutaneous selective hepatic artery infusion of 5-fluorouracil. Surgery 73:118

    PubMed  CAS  Google Scholar 

  118. Ensminer W, Niederhuber J, Dakhil S, Thrall J, Wheeler R (1981) Totally implanted drug delivery system for hepatic arterial chemotherapy. Cancer Treat Rep 65:393–400

    Google Scholar 

  119. Power DG, Kemeny NE (2009) The role of floxuridine in metastatic liver disease. Mol Cancer Ther 8(5):1015–1025

    Article  PubMed  CAS  Google Scholar 

  120. Kemeny N et al (2006) Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481). J Clin Oncol 24(9):1395–1403

    Article  PubMed  CAS  Google Scholar 

  121. Mocellin S, Pilati P, Lise M et al (2007) Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: the end of an era? J Clin Oncol 25:5649–5654

    Article  PubMed  Google Scholar 

  122. Allen PJ, Nissan A, Picon AI et al (2005) Technical complications and durability of hepatic artery infusion pumps for unresectable colorectal liver metastases: an institutional experience of 544 consecutive cases. J Am Coll Surg 201:57–65

    Article  PubMed  Google Scholar 

  123. Northover J, Terblance J (1979) A new look at the arterial supply of the bile duct in man and its surgical implications. Br J Surg 66:379–384

    Article  PubMed  CAS  Google Scholar 

  124. Kemeny N (1992) Is hepatic infusion of chemotherapy effective treatment for liver metastases? Yes! In: DeVita VT, Hellman S, Rosenberg SA (eds) Important advances in oncology, chap 12. J.B. Lippincott Co., New York, pp 207–228

  125. Mitry E, Fields AL, Bleiberg H et al (2008) Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol 26:4906–4911

    Article  PubMed  CAS  Google Scholar 

  126. Power DG, Kemeny NE (2010) The role of adjuvant therapy after resection of colorectal cancer liver-metastases. J Clin Oncol 28(13):2300–2309

    Article  PubMed  CAS  Google Scholar 

  127. Kemeny N, Huang Y, Cohen AM et al (1999) Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 341(27):2039

    Article  PubMed  CAS  Google Scholar 

  128. Kemeny NE, Gonen M (2005) Hepatic arterial infusion after liver resection [7]. N Engl J Med 352(7):734–735

    Article  PubMed  CAS  Google Scholar 

  129. Kemeny MM, Adak S, Gray B et al (2002) Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy—an intergroup study. J Clin Oncol 20(6):1499–1505

    Article  PubMed  Google Scholar 

  130. Lygidakis NJ, Sgourakis G, Vlachos L et al (2001) Metastatic liver disease of colorectal origin: the value of locoregional immunochemotherapy combined with systemic chemotherapy following liver resection. Results of a prospective randomized study. Hepatogastroenterology 48(42):1685–1691

    PubMed  CAS  Google Scholar 

  131. Lorenz M, Muller HH, Schramm H et al (1998) Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. German Cooperative on Liver Metastases (Arbeitsgruppe Lebermetastasen). Ann Surg 228(6):756–762

    Article  PubMed  CAS  Google Scholar 

  132. Kemeny NE, Jarnagin W, Gonen M et al (2005) Phase I trial of hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone (DEX) in combination with systemic oxaliplatin (OXAL), fluorouracil (FU) + leucovorin (LV) after resection of hepatic metastases from colorectal cancer. J Clin Oncol 23(16S):Abstract No: 3579

    Google Scholar 

  133. Kemeny NE, Jarnagin WR, Capanu M, Fong Y, Gewirtz AN, Dematteo RP (2011) D’Angelica MI Randomized phase II trial of adjuvant hepatic arterial infusion and systemic chemotherapy with or without bevacizumab in patients with resected hepatic metastases from colorectal cancer. J Clin Oncol 29:884–889

    Article  PubMed  CAS  Google Scholar 

  134. House MG, Kemeny NE, Gonen M, Fong Y, Allen PJ, Paty PB, DeMatteo RP, Blumgart LH, Jarnagin WR, D’Angelica MI (2011) Comparison of adjuvant systemic chemotherapy with or without hepatic arterial infusional chemotherapy after hepatic resection for metastatic colorectal cancer. Ann Surg 254(6):851–856

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Surgical Oncology, Landmark Medical Center, Woonsocket, RI, USA

    Harold J. Wanebo

  2. Department of Pathology, Surgical Pathology, Rhode Island Hospital, Providence, RI, USA

    Mark LeGolvan

  3. Warren Alpert School of Medicine, Brown University, Providence, RI, USA

    Mark LeGolvan

  4. Division of Colorectal Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Philip B. Paty

  5. Division of Surgical Oncology, University of Michigan, Flint, MI, USA

    Sukamal Saha

  6. Department of Surgery, Cantonal Hospital Olten, Olten, Switzerland

    Markus Zuber

  7. Hepatobiliary Division, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Michael I. D’Angelica

  8. Division of Medical Oncology, Regional Therapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Nancey E. Kemeny

Authors
  1. Harold J. Wanebo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark LeGolvan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Philip B. Paty
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sukamal Saha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Markus Zuber
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael I. D’Angelica
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nancey E. Kemeny
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Harold J. Wanebo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wanebo, H.J., LeGolvan, M., Paty, P.B. et al. Meeting the biologic challenge of colorectal metastases. Clin Exp Metastasis 29, 821–839 (2012). https://doi.org/10.1007/s10585-012-9517-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-012-9517-x

Keywords

Search

Navigation