Current Colorectal Cancer Reports

, Volume 2, Issue 2, pp 85–93 | Cite as

Shifting from clinical to biologic indicators of prognosis after resection of hepatic colorectal metastases

Article

Abstract

Following resection of hepatic colorectal metastases, there are few criteria for predicting which patients have more aggressive disease and are, therefore, more likely to experience recurrence and reduced survival. Traditionally, primary tumor stage, preoperative carcinoembryonic antigen level, time from primary tumor treatment to diagnosis of hepatic metastases (disease-free interval), hepatic tumor size, number of hepatic metastases, and presence of extrahepatic disease have been reported to be predictors of survival after resection. However, the data regarding the prognostic importance of these clinicopathologic factors are inconsistent and conflicting. Therefore, conventional clinicopathologic factors may be inadequate for the purposes of prognostication. More recently, there has been increased interest in identifying biologic indicators that may help better define patients at risk for recurrence after hepatic resection for colorectal metastases. Recent studies have shown that proliferation markers such as p53 expression, tritiated thymidine uptake, thymidylate synthase, Ki-67, and human telomerase reverse transcriptase may be better predictors of outcome after resection of hepatic colorectal metastases. Moreover, tumor response to preoperative chemotherapy may also prove to be a useful predictor of outcome following liver resection for colorectal metastases.

Keywords

Hepatic Resection Hepatic Metastasis Metastatic Colorectal Cancer Colorectal Liver Metastasis Extrahepatic Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References and Recommended Reading

  1. 1.
    Jemal A, Murray T, Ward E, et al.: Cancer statistics, 2005. CA Cancer J Clin 2005, 55:10–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Steele G Jr, Ravikumar TS: Resection of hepatic metastases from colorectal cancer. Biologic perspective. Ann Surg 1989, 210:127–138.PubMedCrossRefGoogle Scholar
  3. 3.
    Jaffe BM, Donegan WL, Watson F, Spratt JS Jr: Factors influencing survival in patients with untreated hepatic metastases. Surg Gynecol Obstet 1968, 127:1–11.PubMedGoogle Scholar
  4. 4.
    Bengmark S, Hafstrom L: The natural history of primary and secondary malignant tumors of the liver. I. The prognosis for patients with hepatic metastases from colonic and rectal carcinoma by laparotomy. Cancer 1969, 23:198–202.PubMedCrossRefGoogle Scholar
  5. 5.
    de Brauw LM, van de Velde CJ, Bouwhuis-Hoogerwerf ML, Zwaveling A: Diagnostic evaluation and survival analysis of colorectal cancer patients with liver metastases. J Surg Oncol 1987, 34:81–86.PubMedCrossRefGoogle Scholar
  6. 6.
    Bengtsson G, Carlsson G, Hafstrom L, Jonsson PE: Natural history of patients with untreated liver metastases from colorectal cancer. Am J Surg 1981, 141:586–589.PubMedCrossRefGoogle Scholar
  7. 7.
    Goslin R, Steele G Jr, Zamcheck N, et al.: Factors influencing survival in patients with hepatic metastases from adenocarcinoma of the colon or rectum. Dis Colon Rectum 1982, 25:749–754.PubMedCrossRefGoogle Scholar
  8. 8.
    Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. Advanced Colorectal Cancer Meta-analysis Project. J Clin Oncol 1992, 10:896–903.Google Scholar
  9. 9.
    Saltz LB, Cox JV, Blanke C, et al.: Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 2000, 343:905–914.PubMedCrossRefGoogle Scholar
  10. 10.
    de Gramont A, Bosset JF, Milan C, et al.: Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. J Clin Oncol 1997, 15:808–815.PubMedGoogle Scholar
  11. 11.
    Douillard JY, Cunningham D, Roth AD, et al.: Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 2000, 355:1041–1047.PubMedCrossRefGoogle Scholar
  12. 12.
    Goldberg RM, Sargent DJ, Morton RF, et al.: A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004, 22:23–30.PubMedCrossRefGoogle Scholar
  13. 13.
    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, 18:2938–2947.PubMedGoogle Scholar
  14. 14.
    Cunningham D, Pyrhonen S, James RD, et al.: Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 1998, 352:1413–1418.PubMedCrossRefGoogle Scholar
  15. 15.
    Rougier P, Van Cutsem E, Bajetta E, et al.: Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet 1998, 352:1407–1412.PubMedCrossRefGoogle Scholar
  16. 16.
    Rothenberg ML, Oza AM, Bigelow RH, et al.: Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial. J Clin Oncol 2003, 21:2059–2069.PubMedCrossRefGoogle Scholar
  17. 17.
    Hurwitz H, Fehrenbacher L, Novotny W, et al.: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004, 350:2335–2342.PubMedCrossRefGoogle Scholar
  18. 18.
    Saltz LB, Meropol NJ, Loehrer PJ Sr, et al.: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 2004, 22:1201–1208.PubMedCrossRefGoogle Scholar
  19. 19.
    Moertel CG, Gunderson LL, Mailliard JA, et al.: Early evaluation of combined fluorouracil and leucovorin as a radiation enhancer for locally unresectable, residual, or recurrent gastrointestinal carcinoma. The North Central Cancer Treatment Group. J Clin Oncol 1994, 12:21–27.PubMedGoogle Scholar
  20. 20.
    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, 230:309–321. This is a large series which outlines a scoring system utilizing various clinical prognostic factors.PubMedCrossRefGoogle Scholar
  21. 21.
    Vauthey JN, Pawlik TM, Abdalla EK, et al.: Is extended hepatectomy for hepatobiliary malignancy justified? Ann Surg 2004, 239:722–732.PubMedCrossRefGoogle Scholar
  22. 22.
    Rosen CB, Nagorney DM, Taswell HF, et al.: Perioperative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma. Ann Surg 1992, 216:493–505.PubMedCrossRefGoogle Scholar
  23. 23.
    Abdalla EK, Vauthey JN, Ellis LM, et al.: Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 2004, 239:818–827.PubMedCrossRefGoogle Scholar
  24. 24.
    Scheele J, Stangl R, Altendorf-Hofmann A: Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg 1990, 77:1241–1246.PubMedCrossRefGoogle Scholar
  25. 25.
    Choti MA, Sitzmann JV, Tiburi MF, et al.: Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 2002, 235:759–766. One of the first publications reporting a clear improving survival in patients undergoing liver resection. Factors impacting prognosis and potential reasons for the improved results are discussed.PubMedCrossRefGoogle Scholar
  26. 26.
    Hughes KS, Rosenstein RB, Songhorabodi S, et al.: Resection of the liver for colorectal carcinoma metastases. A multiinstitutional study of long-term survivors. Dis Colon Rectum 1988, 31:1–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Adson MA, van Heerden JA, Adson MH, et al.: Resection of hepatic metastases from colorectal cancer. Arch Surg 1984, 119:647–651.PubMedGoogle Scholar
  28. 28.
    Schlag P, Hohenberger P, Herfarth C: Resection of liver metastases in colorectal cancer-competitive analysis of treatment results in synchronous versus metachronous metastases. Eur J Surg Oncol 1990, 16:360–365.PubMedGoogle Scholar
  29. 29.
    Gayowski TJ, Iwatsuki S, Madariaga JR, et al.: Experience in hepatic resection for metastatic colorectal cancer: analysis of clinical and pathologic risk factors. Surgery 1994, 116:703–711.PubMedGoogle Scholar
  30. 30.
    Jenkins LT, Millikan KW, Bines SD, et al.: Hepatic resection for metastatic colorectal cancer. Am Surg 1997, 63:605–610.PubMedGoogle Scholar
  31. 31.
    Jamison RL, Donohue JH, Nagorney DM, et al.: Hepatic resection for metastatic colorectal cancer results in cure for some patients. Arch Surg 1997, 132:505–511.PubMedGoogle Scholar
  32. 32.
    Hughes KS, Simon R, Songhorabodi S, et al.: Resection of the liver for colorectal carcinoma metastases: a multiinstitutional study of patterns of recurrence. Surgery 1986, 100:278–284.PubMedGoogle Scholar
  33. 33.
    Scheele J, Stang R, Altendorf-Hofmann A, Paul M: Resection of colorectal liver metastases. World J Surg 1995, 19:59–71.PubMedCrossRefGoogle Scholar
  34. 34.
    Fong Y, Cohen AM, Fortner JG, et al.: Liver resection for colorectal metastases. J Clin Oncol 1997, 15:938–946.PubMedGoogle Scholar
  35. 35.
    Nitti D, Belluco C, Montesco MC, et al.: Nuclear p53 protein expression in resected hepatic metastases from colorectal cancer: an independent prognostic factor of survival. Eur J Cancer 1998, 34:851–855.PubMedCrossRefGoogle Scholar
  36. 36.
    Weber JC, Nakano H, Bachellier P, et al.: Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases? Am J Surg 2001, 182:81–88.PubMedCrossRefGoogle Scholar
  37. 37.
    de Jong KP, Lont HE, Bijma AM, et al.: The effect of partial hepatectomy on tumor growth in rats: in vivo and in vitro studies. Hepatology 1995, 22:1263–1272.PubMedCrossRefGoogle Scholar
  38. 38.
    Gonen M, Hummer A, Zervoudakis A, et al.: Thymidylate synthase expression in hepatic tumors is a predictor of sur vival and progression in patients with resectable metastatic colorectal cancer. J Clin Oncol 2003, 21:406–412.PubMedCrossRefGoogle Scholar
  39. 39.
    Smith DL, Soria JC, Morat L, et al.: Human telomerase reverse transcriptase (hTERT) and Ki-67 are better predictors of sur vival than established clinical indicators in patients undergoing curative hepatic resection for colorectal metastases. Ann Surg Oncol 2004, 11:45–51.PubMedCrossRefGoogle Scholar
  40. 40.
    Domont J, Pawlik TM, Boige V, et al.: Catalytic subunit of human telomerase reverse transcriptase is an independent predictor of sur vival in patients undergoing curative resection of hepatic colorectal metastases: a multicenter analysis. J Clin Oncol 2005, 23:3086–3093. This paper reports on one biologic factor which was shown to be an independent predictor of prognosis.PubMedCrossRefGoogle Scholar
  41. 41.
    Nordlinger B, Guiguet M, Vaillant JC, et al.: Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Francaise de Chirurgie. Cancer 1996, 77:1254–1262.PubMedCrossRefGoogle Scholar
  42. 42.
    Mann CD, Metcalfe MS, Leopardi LN, Maddern GJ: The clinical risk score: emerging as a reliable preoperative prognostic index in hepatectomy for colorectal metastases. Arch Surg 2004, 139:1168–1172.PubMedCrossRefGoogle Scholar
  43. 43.
    Wang JY, Chiang JM, Jeng LB, et al.: Resection of liver metastases from colorectal cancer: are there any truly significant clinical prognosticators? Dis Colon Rectum 1996, 39:847–851.PubMedCrossRefGoogle Scholar
  44. 44.
    Aldrighetti L, Castoldi R, Di Palo S, et al.: [Prognostic factors for long-term outcome of hepatic resection for colorectal liver metastases.] Chir Ital 2005, 57:555–570.PubMedGoogle Scholar
  45. 45.
    Mala T, Bohler G, Mathisen O, et al.: Hepatic resection for colorectal metastases: can preoperative scoring predict patient outcome? World J Surg 2002, 26:1348–1353.PubMedCrossRefGoogle Scholar
  46. 46.
    Fortner JG, Silva JS, Golbey RB, et al.: Multivariate analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer. I. Treatment by hepatic resection. Ann Surg 1984, 199:306–316.PubMedCrossRefGoogle Scholar
  47. 47.
    Doci R, Gennari L, Bignami P, et al.: One hundred patients with hepatic metastases from colorectal cancer treated by resection: analysis of prognostic determinants. Br J Surg 1991, 78:797–801.PubMedCrossRefGoogle Scholar
  48. 48.
    Scheele J, Stangl R, Altendorf-Hofmann A, Gall FP: Indicators of prognosis after hepatic resection for colorectal secondaries. Surgery 1991, 110:13–29.PubMedGoogle Scholar
  49. 49.
    Ekberg H, Tranberg KG, Andersson R, et al.: Determinants of sur vival in liver resection for colorectal secondaries. Br J Surg 1986, 73:727–731.PubMedCrossRefGoogle Scholar
  50. 50.
    Weber SM, Jarnagin WR, DeMatteo RP, et al.: Sur vival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol 2000, 7:643–650.PubMedCrossRefGoogle Scholar
  51. 51.
    Cady B, Stone MD, McDermott WV Jr, et al.: Technical and biological factors in disease-free sur vival after hepatic resection for colorectal cancer metastases. Arch Surg 1992, 127:561–569.PubMedGoogle Scholar
  52. 52.
    Kokudo N, Imamura H, Sugawara Y, et al.: Surgery for multiple hepatic colorectal metastases. J Hepatobiliary Pancreat Surg 2004, 11:84–91.PubMedCrossRefGoogle Scholar
  53. 53.
    Bolton JS, Fuhrman GM: Sur vival after resection of multiple bilobar hepatic metastases from colorectal carcinoma. Ann Surg 2000, 231:743–751.PubMedCrossRefGoogle Scholar
  54. 54.
    Adam R, Pascal G, Castaing D, et al.: Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg 2004, 240:1052–1064. This report is one of the first to implicate response to chemotherapy as an important prognostic factor when considering resection of liver metastases.PubMedCrossRefGoogle Scholar
  55. 55.
    Pawlik TM, Abdalla EK, Ellis LM, et al.: Debunking dogma: surgery for four or more colorectal liver metastases is justified. J Gastro Surg 2006, In press.Google Scholar
  56. 56.
    Nagakura S, Shirai Y, Yamato Y, et al.: Simultaneous detection of colorectal carcinoma liver and lung metastases does not warrant resection. J Am Coll Surg 2001, 193:153–160.PubMedCrossRefGoogle Scholar
  57. 57.
    Elias D, Sideris L, Pocard M, et al.: Results of R0 resection for colorectal liver metastases associated with extrahepatic disease. Ann Surg Oncol 2004, 11:274–280.PubMedCrossRefGoogle Scholar
  58. 58.
    Ferrero A, Polastri R, Muratore A, et al.: Extensive resections for colorectal liver metastases. J Hepatobiliary Pancreat Surg 2004, 11:92–96.PubMedCrossRefGoogle Scholar
  59. 59.
    Elias D, Ouellet JF, Bellon N, et al.: Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases. Br J Surg 2003, 90:567–574.PubMedCrossRefGoogle Scholar
  60. 60.
    Inoue M, Kotake Y, Nakagawa K, et al.: Surgery for pulmonary metastases from colorectal carcinoma. Ann Thorac Surg 2000, 70:380–383.PubMedCrossRefGoogle Scholar
  61. 61.
    McAfee MK, Allen MS, Trastek VF, et al.: Colorectal lung metastases: results of surgical excision. Ann Thorac Surg 1992, 53:780–786.PubMedCrossRefGoogle Scholar
  62. 62.
    Sakamoto T, Tsubota N, Iwanaga K, et al.: Pulmonary resection for metastases from colorectal cancer. Chest 2001, 119:1069–1072.PubMedCrossRefGoogle Scholar
  63. 63.
    Mansel JK, Zinsmeister AR, Pairolero PC, Jett JR: Pulmonary resection of metastatic colorectal adenocarcinoma. A ten year experience. Chest 1986, 89:109–112.PubMedGoogle Scholar
  64. 64.
    Inoue M, Ohta M, Iuchi K, et al.: Benefits of surgery for patients with pulmonary metastases from colorectal carcinoma. Ann Thorac Surg 2004, 78:238–244.PubMedCrossRefGoogle Scholar
  65. 65.
    Cady B, Stone MD: The role of surgical resection of liver metastases in colorectal carcinoma. Semin Oncol 1991, 18:399–406.PubMedGoogle Scholar
  66. 66.
    Belluco C, Guillem JG, Kemeny N, et al.: p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases. J Clin Oncol 1996, 14:2696–2701.PubMedGoogle Scholar
  67. 67.
    Costa A, Doci R, Mochen C, et al.: Cell proliferation-related markers in colorectal liver metastases: correlation with patient prognosis. J Clin Oncol 1997, 15:2008–2014.PubMedGoogle Scholar
  68. 68.
    Petrowsky H, Sturm I, Graubitz O, et al.: Relevance of Ki-67 antigen expression and K-ras mutation in colorectal liver metastases. Eur J Surg Oncol 2001, 27:80–87.PubMedCrossRefGoogle Scholar
  69. 69.
    Lind DS, Parker GA, Horsley JS 3rd, et al.: Formal hepatic resection of colorectal liver metastases. Ploidy and prognosis. Ann Surg 1992, 215:677–684.PubMedCrossRefGoogle Scholar
  70. 70.
    Crowe PJ, Yang JL, Berney CR, et al.: Genetic markers of sur vival and liver recurrence after resection of liver metastases from colorectal cancer. World J Surg 2001, 25:996–1001.PubMedCrossRefGoogle Scholar
  71. 71.
    Saw RP, Koorey D, Painter D, et al.: p53, DCC and thymidylate synthase as predictors of sur vival after resection of hepatic metastases from colorectal cancer. Br J Surg 2002, 89:1409–1415.PubMedCrossRefGoogle Scholar
  72. 72.
    Hollstein M, Sidransky D, Vogelstein B, Harris CC: p53 mutations in human cancers. Science 1991, 253:49–53.PubMedCrossRefGoogle Scholar
  73. 73.
    Kastan MB, Onyekwere O, Sidransky D, et al.: Participation of p53 protein in the cellular response to DNA damage. Cancer Res 1991, 51:6304–6311.PubMedGoogle Scholar
  74. 74.
    Sturm I, Kohne CH, Wolff G, et al.: Analysis of the p53/BA X pathway in colorectal cancer: low BA X is a negative prognostic factor in patients with resected liver metastases. J Clin Oncol 1999, 17:1364–1374.PubMedGoogle Scholar
  75. 75.
    Hasegawa H, Ueda M, Furukawa K, et al.: p53 gene mutations in early colorectal carcinoma. De novo vs. adenoma-carcinoma sequence. Int J Cancer 1995, 64:47–51.PubMedCrossRefGoogle Scholar
  76. 76.
    Wang A, Yoshimi N, Ino N, et al.: WAF1 expression and p53 mutations in human colorectal cancers. J Cancer Res Clin Oncol 1997, 123:118–123.PubMedCrossRefGoogle Scholar
  77. 77.
    Pricolo VE, Finkelstein SD, Hansen K, et al.: Mutated p53 gene is an independent adverse predictor of survival in colon carcinoma. Arch Surg 1997, 132:371–375.PubMedGoogle Scholar
  78. 78.
    Kastrinakis WV, Ramchurren N, Rieger KM, et al.: Increased incidence of p53 mutations is associated with hepatic metastasis in colorectal neoplastic progression. Oncogene 1995, 11:647–652.PubMedGoogle Scholar
  79. 79.
    Ofner D, Riehemann K, Maier H, et al.: Immunohistochemically detectable bcl-2 expression in colorectal carcinoma: correlation with tumour stage and patient survival. Br J Cancer 1995, 72:981–985.PubMedGoogle Scholar
  80. 80.
    Johnston PG, Fisher ER, Rockette HE, et al.: The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer. J Clin Oncol 1994, 12:2640–2647.PubMedGoogle Scholar
  81. 81.
    Lenz HJ, Danenberg KD, Leichman CG, et al.: p53 and thymidylate synthase expression in untreated stage II colon cancer: associations with recurrence, survival, and site. Clin Cancer Res 1998, 4:1227–1234.PubMedGoogle Scholar
  82. 82.
    Allegra C: Thymidylate synthase levels: prognostic, predictive, or both? J Clin Oncol 2002, 20:1711–1713.PubMedCrossRefGoogle Scholar
  83. 83.
    Allegra CJ, Parr AL, Wold LE, et al.: Investigation of the prognostic and predictive value of thymidylate synthase, p53, and Ki-67 in patients with locally advanced colon cancer. J Clin Oncol 2002, 20:1735–1743.PubMedCrossRefGoogle Scholar
  84. 84.
    Aschele C, Debernardis D, Casazza S, et al.: Immunohistochemical quantitation of thymidylate synthase expression in colorectal cancer metastases predicts for clinical outcome to fluorouracil-based chemotherapy. J Clin Oncol 1999, 17:1760–1770.PubMedGoogle Scholar
  85. 85.
    Davies MM, Johnston PG, Kaur S, Allen-Mersh TG: Colorectal liver metastasis thymidylate synthase staining correlates with response to hepatic arterial floxuridine. Clin Cancer Res 1999, 5:325–328.PubMedGoogle Scholar
  86. 86.
    Link KH, Kornmann M, Butzer U, et al.: Thymidylate synthase quantitation and in vitro chemosensitivity testing predicts responses and survival of patients with isolated nonresectable liver tumors receiving hepatic arterial infusion chemotherapy. Cancer 2000, 89:288–296.PubMedCrossRefGoogle Scholar
  87. 87.
    Moyzis RK, Buckingham JM, Cram LS, et al.: A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci U S A 1988, 85:6622–6626.PubMedCrossRefGoogle Scholar
  88. 88.
    Blackburn EH: Structure and function of telomeres. Nature 1991, 350:569–573.PubMedCrossRefGoogle Scholar
  89. 89.
    Greider CW: Telomeres. Curr Opin Cell Biol 1991, 3:444–451.PubMedCrossRefGoogle Scholar
  90. 90.
    Yan P, Benhattar J, Seelentag W, et al.: Immunohistochemical localization of hTERT protein in human tissues. Histochem Cell Biol 2004, 121:391–397.PubMedCrossRefGoogle Scholar
  91. 91.
    Shore D: Telomerase and telomere-binding proteins: controlling the endgame. Trends Biochem Sci 1997, 22:233–235.PubMedCrossRefGoogle Scholar
  92. 92.
    Vaziri H, Dragowska W, Allsopp RC, et al.: Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci U S A 1994, 91:9857–9860.PubMedCrossRefGoogle Scholar
  93. 93.
    Lindsey J, McGill NI, Lindsey LA, et al.: In vivo loss of telomeric repeats with age in humans. Mutat Res 1991, 256:45–48.PubMedGoogle Scholar
  94. 94.
    Shay JW, Wright WE: Telomerase activity in human cancer. Curr Opin Oncol 1996, 8:66–71.PubMedGoogle Scholar
  95. 95.
    Yang Y, Chen Y, Zhang C, et al.: Nucleolar localization of hTERT protein is associated with telomerase function. Exp Cell Res 2002, 277:201–209.PubMedCrossRefGoogle Scholar
  96. 96.
    Etheridge KT, Banik SS, Armbruster BN, et al.: The nucleolar localization domain of the catalytic subunit of human telomerase. J Biol Chem 2002, 277:24764–24770.PubMedCrossRefGoogle Scholar
  97. 97.
    Lantuejoul S, Soria JC, Moro-Sibilot D, et al.: Differential expression of telomerase reverse transcriptase (hTERT) in lung tumours. Br J Cancer 2004, 90:1222–1229.PubMedCrossRefGoogle Scholar
  98. 98.
    Kim NW, Piatyszek MA, Prowse KR, et al.: Specific association of human telomerase activity with immortal cells and cancer. Science 1994, 266:2011–2015.PubMedCrossRefGoogle Scholar
  99. 99.
    Yoo J, Park SY, Kang SJ, et al.: Expression of telomerase activity, human telomerase RNA, and telomerase reverse transcriptase in gastric adenocarcinomas. Mod Pathol 2003, 16:700–707.PubMedCrossRefGoogle Scholar
  100. 100.
    Kanaya T, Kyo S, Takakura M, et al.: hTERT is a critical determinant of telomerase activity in renal-cell carcinoma. Int J Cancer 1998, 78:539–543.PubMedCrossRefGoogle Scholar
  101. 101.
    Liu YC, Chen CJ, Wu HS, et al.: Telomerase and c-myc expression in hepatocellular carcinomas. Eur J Surg Oncol 2004, 30:384–390.PubMedCrossRefGoogle Scholar
  102. 102.
    Niiyama H, Mizumoto K, Sato N, et al.: Quantitative analysis of hTERT mRNA expression in colorectal cancer. Am J Gastroenterol 2001, 96:1895–1900.PubMedCrossRefGoogle Scholar
  103. 103.
    Chadeneau C, Hay K, Hirte HW, et al.: Telomerase activity associated with acquisition of malignancy in human colorectal cancer. Cancer Res 1995, 55:2533–2536.PubMedGoogle Scholar
  104. 104.
    Stremmel C, Wein A, Hohenberger W, Reingruber B: DNA microarrays: a new diagnostic tool and its implications in colorectal cancer. Int J Colorectal Dis 2002, 17:131–136.PubMedCrossRefGoogle Scholar
  105. 105.
    Mehta KR, Nakao K, Zuraek MB, et al.: Fractional genomic alteration detected by array-based comparative genomic hybridization independently predicts survival after hepatic resection for metastatic colorectal cancer. Clin Cancer Res 2005, 11:1791–1797.PubMedCrossRefGoogle Scholar
  106. 106.
    Tanaka K, Adam R, Shimada H, et al.: Role of neoadjuvant chemotherapy in the treatment of multiple colorectal metastases to the liver. Br J Surg 2003, 90:963–969.PubMedCrossRefGoogle Scholar
  107. 107.
    Weber JC, Navarra G, Jiao LR, et al.: New technique for liver resection using heat coagulative necrosis. Ann Surg 2002, 236:560–563.PubMedCrossRefGoogle Scholar
  108. 108.
    Parikh AA, Gentner B, Wu TT, et al.: Perioperative complications in patients undergoing major liver resection with or without neoadjuvant chemotherapy. J Gastrointest Surg 2003, 7:1082–1088.PubMedCrossRefGoogle Scholar
  109. 109.
    Allen PJ, Kemeny N, Jarnagin W, et al.: Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases. J Gastrointest Surg 2003, 7:109–117.PubMedCrossRefGoogle Scholar
  110. 110.
    Nordlinger B, Quilichini MA, Parc R, et al.: Hepatic resection for colorectal liver metastases. Influence on survival of preoperative factors and surgery for recurrences in 80 patients. Ann Surg 1987, 205:256–263.PubMedCrossRefGoogle Scholar
  111. 111.
    Fong Y, Saldinger PF, Akhurst T, et al.: Utility of 18F-FDG positron emission tomography scanning on selection of patients for resection of hepatic colorectal metastases. Am J Surg 1999, 178:282–287.PubMedCrossRefGoogle Scholar

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© Current Science Inc. 2006

Authors and Affiliations

  1. 1.Department of SurgeryJohns Hopkins HospitalBaltimoreUSA

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