Surgery Today

, Volume 40, Issue 4, pp 287–294 | Cite as

Strategies for treating liver metastasis from gastric cancer

  • Yoshihiro Kakeji
  • Masaru Morita
  • Yoshihiko Maehara
Review Article

Abstract

The prognosis of patients with liver metastasis from gastric cancer is dismal. This article reviews the characteristics of gastric cancer metastasizing to the liver, and multimodality of treatments. Differentiated adenocarcinoma, poorly differentiated adenocarcinoma with a medullary growth pattern, and special types, including endocrine carcinoma and hepatoid carcinoma, are likely to metastasize to the liver. The overexpression of growth factors or adhesion molecules is clinically significant for liver metastasis. Surgery for liver metastases arising from gastric adenocarcinoma is reasonable if a complete resection seems feasible after careful preoperative staging. A hepatic resection should always be considered as an option for gastric cancer patients with hepatic metastases. Newer generation cytotoxic agents such as S-1, irinotecan, and taxanes show promising activity for patients with metastases. Adjuvant chemotherapy or molecular targeted therapy will provide significant benefits to patients in the future.

Key words

Gastric cancer Hepatic resection Liver metastasis Adjuvant chemotherapy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    American Cancer Society. Global cancer facts and figures 2007. http://www.cancer.org/downloads/STT/Global_Facts_and_Figs._2007_rev2.pdf. Accessed 16 Jun 2009.
  2. 2.
    Ministry of Health, Labor and Welfare, Japan. Figures for vital statistics in 2007. http://www.mhlw.go.jp/toukei/saikin/hw/jinkou/kakutei07/hyo7.html. Accessed 16 Jun 2009.
  3. 3.
    Sasako M, Saka M, Fukagawa T, Katai H, Sano T. Modern surgery for gastric cancer — Japanese perspective. Scand J Surg 2006;95:232–235.PubMedGoogle Scholar
  4. 4.
    Douglass HO Jr, Hundahl SA, Macdonald JS, Khatri VP. Gastric cancer: D2 dissection or low Maruyama Index-based surgery — a debate. Surg Oncol Clin N Am 2007;16:133–155.CrossRefPubMedGoogle Scholar
  5. 5.
    Sano T. Tailoring treatments for curable gastric cancer. Br J Surg 2007;94:263–264.CrossRefPubMedGoogle Scholar
  6. 6.
    Sano T, Yamamoto S, Kurokawa Y, Nashimoto A, Kurita A, Hiratsuka M, et al. D2 lymphadenectomy alone or with paraaortic nodal dissection for gastric cancer. N Engl J Med 2008;359:453–462.CrossRefPubMedGoogle Scholar
  7. 7.
    Hu JK, Yang K, Zhang B, Chen XZ, Chen ZX, Chen JP. D2 plus para-aortic lymphadenectomy versus standardized D2 lymphadenectomy in gastric cancer surgery. Surg Today 2009;39:207–213.CrossRefPubMedGoogle Scholar
  8. 8.
    Marrelli D, Roviello F, De Stefano A, Fotia G, Gilberto C, Garosi L, et al. Risk factors for liver metastases after curative surgical procedures for gastric cancer: a prospective study of 208 patients treated with surgical resection. J Am Coll Surg 2004;198:51–58.CrossRefPubMedGoogle Scholar
  9. 9.
    Okano K, Maeba T, Ishimura K, Karasawa Y, Goda F, Wakabayashi H, et al. Hepatic resection for metastatic tumors from gastric cancer. Ann Surg 2002;235:86–91.CrossRefPubMedGoogle Scholar
  10. 10.
    Sakamoto Y, Ohyama S, Yamamoto J, Yamada K, Seki M, Ohta K, et al. Surgical resection of liver metastases of gastric cancer: an analysis of a 17-year experience with 22 patients. Surgery 2003;133:507–511.CrossRefPubMedGoogle Scholar
  11. 11.
    Sakamoto Y, Sano T, Shimada K, Esaki M, Saka M, Fukagawa T, et al. Favorable indications for hepatectomy in patients with liver metastasis from gastric cancer. J Surg Oncol 2007;95:534–539.CrossRefPubMedGoogle Scholar
  12. 12.
    Nakanishi H, Yasui K, Ikehara Y, Yokoyama H, Munesue S, Kodera Y, et al. Establishment and characterization of three novel human gastric cancer cell lines with differentiated intestinal phenotype derived from liver metastasis. Clinical & Experimental Metastasis 2005;22:137–147.CrossRefGoogle Scholar
  13. 13.
    Terracciano LM, Glatz K, Mhawech P. Hepatoid adenocarcinoma with liver metastasis mimicking hepatocellular carcinoma: An immunohistochemical and molecular study of eight cases. Am J Surg Pathol 2003;27:1302–1312.CrossRefPubMedGoogle Scholar
  14. 14.
    Adachi Y, Tsuchihashi J, Shiraishi N. AFP-producing gastric carcinoma: Multivariate analysis of prognostic factors in 270 patients. Oncology 2003;65:95–101.CrossRefPubMedGoogle Scholar
  15. 15.
    Gao YB, Zhang DF, Jin XL, Xiao JC. Preliminary study on the clinical and pathological relevance of gastric hepatoid adenocarcinoma. J Dig Dis 2007;8:23–28.CrossRefPubMedGoogle Scholar
  16. 16.
    Maehara Y, Moriguchi S, Kakeji Y, Kohnoe S, Korenaga D, Haraguchi M, et al. Pertinent risk factors and gastric carcinoma with synchronous peritoneal dissemination or liver metastasis. Surgery 1991;110:820–823.PubMedGoogle Scholar
  17. 17.
    Amemiya H, Kono K, Itakura J. c-Met expression in gastric cancer with liver metastasis. Oncology 2002;63(3):286–296.CrossRefPubMedGoogle Scholar
  18. 18.
    Kakeji Y, Koga T, Sumiyoshi Y, Shibahara K, Oda S, Maehara Y, et al. Clinical significance of vascular endothelial growth factor expression in gastric cancer. J Exp Clin Cancer Res 2002;21:125–129.PubMedGoogle Scholar
  19. 19.
    Maruo Y, Gochi A, Kaihara A. ICAM-1 expression and the soluble ICAM-1 level for evaluating the metastatic potential of gastric cancer. Int J Cancer 2002;100(4):486–490.CrossRefPubMedGoogle Scholar
  20. 20.
    Mayer B, Lorenz C, Babic R. Expression of leukocyte cell adhesion molecules on gastric carcinomas: Possible involvement of LFA-3 expression in the development of distant metastases. Int J Cancer 1995;64(6):415–423.CrossRefPubMedGoogle Scholar
  21. 21.
    Giordano S, Ponzetto C, Di Renzo MF, Cooper CS, Comoglio PM. Tyrosine kinase receptor indistinguishable from the c-met protein. Nature 1989;339:155–156.CrossRefPubMedGoogle Scholar
  22. 22.
    Giordano S, Di Renzo MF, Narsimhan RP, Cooper CS, Rosa C, Comoglio PM. Biosynthesis of the protein encoded by the c-met protooncogene. Oncogene 1989;4:1383–1388.PubMedGoogle Scholar
  23. 23.
    Bussolino F, Di Renzo MF, Ziche M, Bocchietto E, Olivero M, Naldini L, et al. Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. J Cell Biol 1992;119:629–641.CrossRefPubMedGoogle Scholar
  24. 24.
    Ferrara N, Houck KA, Jakeman LB, Winer J, Leung DW. The vascular endothelial growth factor family of polypeptides. J Cell Biochem 1991;47:211–218.CrossRefPubMedGoogle Scholar
  25. 25.
    Simmons D, Makgoba MW, Seed B. ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature 1988;331:624–627.CrossRefPubMedGoogle Scholar
  26. 26.
    Marlin SD, Spriger TA. Purified intercellular adhesion molecule 1 (ICAM-1) is a ligand for lymphocyte function-associated antigen-1 (LFA-1). Cell 1987;51:813–819.CrossRefPubMedGoogle Scholar
  27. 27.
    Dustin ML, Rothlein R, Bhan AK, Dimarello CA, Springer TA. Induction by IL-1 and interferon-gamma: tissue distribution, biochemistry and function of a natural adherence molecule (ICAM-1). J Immunol 1986;137:245–254.PubMedGoogle Scholar
  28. 28.
    Staunton DE, Marlin SD, Stratowa C, Dustin ML, Springer TA. Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 1988;52:925–933.CrossRefPubMedGoogle Scholar
  29. 29.
    Makgoba MW, Sanders ME, Shaw S. The CD-2-LFA-3 and LFA 1-ICAM pathways: relevance to T-cell recognition. Immunol Today 1989;10:417–422.CrossRefPubMedGoogle Scholar
  30. 30.
    Garcia-Barcina M, Lukomska B, Gawron W, Winnock M, Viral-Vanaccocha F, Bioulac-Sage P, et al. Expression of cell adhesion molecules on liver-associated lymphocytes and their ligands on sinusoidal lining cells in patients with benign or malignant disease. Am J Pathol 1995;146:12406–12413.Google Scholar
  31. 31.
    Volpes R, van der Oord JJ, Desmet VJ. Immunohistochemical study of adhesion molecules in liver inflammation. Hepatology 1990;12:59–65.CrossRefPubMedGoogle Scholar
  32. 32.
    Nakanishi H, Yasui K, Yamagata S. Establishment and characterization of a new spontaneous metastasis model of human gastric carcinoma in nude mice. Jpn J Cancer Res 1991;82(8):927–933.PubMedGoogle Scholar
  33. 33.
    Yamaguchi K, Ura H, Yasoshima T. Liver metastatic model for human gastric cancer established by orthotopic tumor cell implantation. World J Surg 2001;25(2):131–137.CrossRefPubMedGoogle Scholar
  34. 34.
    Shen XH, Jin WN, Cui H, Cui X, Noh SH, Chung HC, et al. Cellular adjustment of gastric cancer for hepatic metastasis in successive orthotopic implantation model. Cancer Biol Ther 2006;5:1313–1319.CrossRefPubMedGoogle Scholar
  35. 35.
    Koga S, Kawaguchi H, Kishimoto H, Tanaka K, Miyano Y, Kimura O, et al. Therapeutic significance of noncurative gastrectomy for gastric cancer with liver metastasis. Am J Surg 1980;140:356–359.CrossRefPubMedGoogle Scholar
  36. 36.
    Shirabe K, Shimada M, Matsumata T, Higashi H, Yakeishi Y, Wakiyama S, et al. Analysis of the prognostic factors for liver metastasis of gastric cancer after hepatic resection: a multi-institutional study of the indications for resection. Hepatogastroenterology 2003;50:1560–1563.PubMedGoogle Scholar
  37. 37.
    Ochiai T, Sasako M, Mizuno S, Kinoshita T, Takayama T, Kosuge T, et al. Hepatic resection for metastatic tumours from gastric cancer: analysis of prognostic factors. Br J Surg 1994;81:1175–1178.CrossRefPubMedGoogle Scholar
  38. 38.
    Koga R, Yamamoto J, Ohyama S, Saiura A, Seki M, Seto Y, et al. Liver resection for metastatic gastric cancer: experience with 42 patients including eight long-term survivors. Jpn J Clin Oncol 2007;37:836–842.CrossRefPubMedGoogle Scholar
  39. 39.
    Miyazaki M, Itoh H, Nakagawa K, Ambiru S, Shimizu H, Togawa A, et al. Hepatic resection of liver metastases from gastric carcinoma. Am J Gastroenterol 1997;92:490–493.PubMedGoogle Scholar
  40. 40.
    Ambiru S, Miyazaki M, Ito H, Nakagawara K, Shimizu H, Yoshidome H, et al. Benefits and limits of hepatic resection for gastric metastases. Am J Surg 2001;181:279–283.CrossRefPubMedGoogle Scholar
  41. 41.
    Cheon SH, Rha SY, Jeung HC, Im CK, Kim SH, Kim HR, et al. Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases. Ann Oncol 2008;19:1146–1153.CrossRefPubMedGoogle Scholar
  42. 42.
    Chen MH, Yang W, Yan K, Gao W, Dai Y, Wang YB, et al. Treatment efficacy of radiofrequency ablation of 338 patients with hepatic malignant tumor and the relevant complications. World J Gastroenterol 2005;11:6395–6401.PubMedGoogle Scholar
  43. 43.
    Iannitti DA, Dupuy DE, Mayo-Smith WW, Murphy B. Hepatic radiofrequency ablation. Arch Surg 2002;137:422–426; discussion 427.CrossRefPubMedGoogle Scholar
  44. 44.
    Yamakado K, Nakatsuka A, Takaki H, Mori Y, Tonouchi H, Kusunoki M, et al. Prospective study of arterial infusion chemotherapy followed by radiofrequency ablation for the treatment of liver metastasis of gastric cancer. J Vasc Interv Radiol 2005;16:1747–1751.PubMedGoogle Scholar
  45. 45.
    Carditello A, Scisca C, Stilo F, Parisi A, Basile M. The possible role of radiofrequency as complementary treatment of locally advanced gastric cancer. Ann Ital Chir 2005;76:39–41.PubMedGoogle Scholar
  46. 46.
    Gannon CJ, Curley SA. The role of focal liver ablation in the treatment of unresectable primary and secondary malignant liver tumors. Semin Radiat Oncol 2005;15:265–272.CrossRefPubMedGoogle Scholar
  47. 47.
    An JY, Kim JY, Choi MG, Noh JH, Choi D, Sohn TS, et al. Radiofrequency ablation for hepatic metastasis from gastric adenocarcinoma. Yonsei Med J 2008;49:1046–1051.CrossRefPubMedGoogle Scholar
  48. 48.
    Shirasaka T, Shimamato Y, Ohshimo H, Yamaguchi M, Kato T, Yonekura K, et al. Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumour selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs 1996;7:548–557.CrossRefPubMedGoogle Scholar
  49. 49.
    Sugimachi K, Maehara Y, Horikoshi N, Shimada Y, Sakata Y, Mitachi Y, et al. An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. Oncology 1999;57:202–210.CrossRefPubMedGoogle Scholar
  50. 50.
    Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, Mitachi Y, Taguchi T. Late phase II study of novel oral fluoropyrimidine aniticancer drug S-1 (1M tegafur-0.4M gimestat-1M otastat potassium) in advanced gastric cancer patients. Eur J Cancer 1998;34:1715–1720.CrossRefPubMedGoogle Scholar
  51. 51.
    Boku N, Yamamoto S, Shirao K, Doi T, Sawaki A, Koizumi W, et al. Randomized phase III study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer. (JCOG 9912) Proc Am Soc Clin Oncol 2007;LBA4513 (abstract).Google Scholar
  52. 52.
    Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 2008;9:215–221.CrossRefPubMedGoogle Scholar
  53. 53.
    Imamura H, Iishi H, Tsuburaya A, Hatake K, Imamoto H, Esaki T, et al. Randomized phase III study of irinotecan plus S-1 (IRIS) versus S-1 alone as first-line treatment for advanced gastric cancer (GC0301/TOP-002). Proc Gastrointestinal Cancers Symposium 2008;4 (abstract).Google Scholar
  54. 54.
    Japan Clinical Cancer Research Organization. A Phase III study of docetaxel and S-1 versus S-1 in the treatment of advanced gastric cancer. https://center.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000000317&type= summary&language=J. Accessed 16 Jun 2009.
  55. 55.
    Yoshida K, Ninomiya M, Takakura N, Hirabayashi N, Takiyama W, Sato Y, et al. Phase II study of docetaxel and S-1 combination therapy for advanced or recurrent gastric cancer. Clin Cancer Res 2006;12:3402–3407.CrossRefPubMedGoogle Scholar
  56. 56.
    Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil in comparison to cisplatin and fluorouracil as first line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 2006;24:4991–4997.CrossRefPubMedGoogle Scholar
  57. 57.
    Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 2008;358:36–46.CrossRefPubMedGoogle Scholar
  58. 58.
    Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol 2009;20:666–673.CrossRefPubMedGoogle Scholar
  59. 59.
    Ganeshan A, Upponi S, Hon LQ, Warakaulle D, Uberoi R. Hepatic arterial infusion of chemotherapy: the role of diagnostic and interventional radiology. Ann Oncol 2008;19:847–851.CrossRefPubMedGoogle Scholar
  60. 60.
    Yonemura Y, Matsuki N, Sakuma H, Katayama K, Sawa T, Fujimura T, et al. Effect of intra-hepatoarterial infusion of MMC and CDDP for gastric cancer patients with liver metastases. Surg Today 1992;22:253–259.CrossRefPubMedGoogle Scholar
  61. 61.
    Arai Y, Endo T, Sone Y, Tohyama N, Inaba Y, Ariyoshi Y, et al. Management of patients with unresectable liver metastases from colorectal and gastric cancer employing an implantable port system. Cancer Chemother Pharmacol 1992;31(suppl I):S99–102.CrossRefPubMedGoogle Scholar
  62. 62.
    Ojima H, Ootake S, Yokobori T, Mochida Y, Hosouchi Y, Nishida Y, et al. Treatment of multiple liver metastasis from gastric carcinoma. World J Surg Oncol 2007;5:70.CrossRefPubMedGoogle Scholar
  63. 63.
    Kumada T, Arai Y, Itoh K, Takayasu Y, Nakamura K, Ariyoshi Y, et al. Phase II study of combined administration of 5-fluorouracil, epirubicin and mitomycin-c by hepatic artery infusion in patients with liver metastases of gastric cancer. Oncology 1999;57:216–223.CrossRefPubMedGoogle Scholar
  64. 64.
    Johansson, C-J. Pharmacokinetic rationale for chemotherapeutic drugs combined with intra-arterial degradable starch microspheres (Spherex(R)). Clin Pharmacokinet 1996;31:231–240.CrossRefPubMedGoogle Scholar
  65. 65.
    Hirasawa T, Asahara S, Fujisaki S, Kuraoka K, Takano K, Kamei A, et al. Transcatheter arterial chemoembolization (TACE) using degradable starch microspheres (DSM) for metastatic liver tumors in patients with gastric cancer (in Japanese with English abstract). J Jpn Soc Gastroenterol 2008;105:367–372.Google Scholar
  66. 66.
    Chang YC, Nagasue N, Abe S, Taniura H, Kumar DD, Nakamura T. Comparison between the clinicopathologic features of AFPpositive and AFP-negative gastric cancers. Am J Gastroenterol 1992;87:321–325.PubMedGoogle Scholar
  67. 67.
    Mihmanli M, Dilege E, Demir U, Coskun H, Eroglu T, Uysalol MD. The use of tumor markers as predictors of prognosis in gastric cancer. Hepatogastroenterology 2004;51:1544–1547.PubMedGoogle Scholar
  68. 68.
    Reynoso G, Chu TM, Holyoke D, Cohen E, Nemoto T, Wang JJ, et al. Carcinoembryonic antigen in patients with different cancers. JAMA 1972;220:361–365.CrossRefPubMedGoogle Scholar
  69. 69.
    Nakagoe T, Sawai T, Tsuji T, Jibiki M, Nanashima A, Yamaguchi H, et al. Pre-operative serum levels of sialyl Tn antigen predict liver metastasis and poor prognosis in patients with gastric cancer. Eur J Surg Oncol 2001;27:731–739.CrossRefPubMedGoogle Scholar
  70. 70.
    Santeusanio G, Peronace L, Castagna G, De Muro G, Santi D, D’Orazio A, et al. Immunohistochemical study of carcinoembryonic antigen (CEA) in gastric tumors: correlation with preoperative serum levels, histologic type, and grade of anaplasia of the tumor. J Surg Oncol 1988;37:13–19.CrossRefPubMedGoogle Scholar
  71. 71.
    Maehara Y, Kusumoto T, Takahashi I, Kakeji Y, Baba H, Akazawa K, et al. Predictive value of preoperative carcinoembryonic antigen levels for the prognosis of patients with welldifferentiated gastric cancer. A multivariate analysis. Oncology 1994;51:234–237.CrossRefPubMedGoogle Scholar
  72. 72.
    Ishigami S, Natsugoe S, Hokita S, Che X, Tokuda K, Nakajo A, et al. Clinical importance of preoperative carcinoembryonic antigen and carbohydrate antigen 19–9 levels in gastric cancer. J Clin Gastroenterol 2001;32:41–44.CrossRefPubMedGoogle Scholar
  73. 73.
    Choi SR, Jang JS, Lee JH, Roh MH, Kim MC, Lee WS, et al. Role of serum tumor markers in monitoring for recurrence of gastric cancer following radical gastrectomy. Dig Dis Sci 2006;51:2081–2086.CrossRefPubMedGoogle Scholar
  74. 74.
    Korenaga D, Saeki H, Mawatari K, Orita H, Maekawa S, Ikeda T, et al. Serum carcinoembryonic antigen concentration doubling time correlates with tumor biology and life expectancy in patients with recurrent gastrointestinal carcinoma. Arch Surg 1997;132:188–194.PubMedGoogle Scholar
  75. 75.
    Seo JH, Choi CW, Kim BS, Shin SW, Kim YH, Kim JS, et al. Follow-up study of peripheral blood carcinoembryonic antigen mRNA using reverse transcription-polymerase chain reaction as an early marker of clinical recurrence in patients with curatively resected gastric cancer. Am J Clin Oncol 2005;28:24–29.CrossRefPubMedGoogle Scholar
  76. 76.
    Motoyama T, Aizawa K, Watanabe H, Fukase M, Saito K. α-Fetoprotein-producing gastric carcinomas: A comparative study of three different subtypes. Acta Pathol Jpn 1 1993;43:654–661.Google Scholar
  77. 77.
    Kono K, Amemiya H, Sekikawa T, Iizuka H, Takahashi A, Fujii H, et al. Clinicopathologic features of gastric cancers producing alpha-fetoprotein. Dig Surg 2002;19:359–365.CrossRefPubMedGoogle Scholar
  78. 78.
    Amemiya H, Kono K, Mori Y, Takahashi A, Ichihara F, Iizuka H, et al. High frequency of c-Met expression in gastric cancers producing α-fetoprotein. Oncology 2 2000;59:145–151.CrossRefGoogle Scholar
  79. 79.
    Matsumoto K, Nakamura T. Hepatocyte growth factor as a tissue organizer for organogenesis and regeneration. Biochem Biophys Res Commun 1997;239:639–644.CrossRefPubMedGoogle Scholar
  80. 80.
    Matsumoto K, Nakamura T. Hepatocyte growth factor: molecular structure, roles in liver regeneration and other biological functions. Crit Rev Oncogen 1992;3:27–54.Google Scholar
  81. 81.
    Koide N, Nishio A, Igarashi J, Kajikawa S, Adachi W, Amano J. Alpha-fetoprotein-producing gastric cancer: Histochemical analysis of cell proliferation, apoptosis and angiogenesis. Am J Gastroenterol 1999;94:1658–1663.PubMedGoogle Scholar
  82. 82.
    Fujii H, Ichikawa K, Takagaki T, Nakanishi Y, Ikegami M, Hirose S, et al. Genetic evolution of [alpha] fetoprotein producing gastric cancer. J Clin Pathol 2003;56:942–949.CrossRefPubMedGoogle Scholar
  83. 83.
    Nakagoe T, Sawai T, Tsuji T, Jibiki M, Nanashima A, Yamaguchi H, et al. Difference in prognostic value between sialyl Lewisa and sialyl Lewisx antigen levels in the preoperative serum of gastric cancer patients. J Clin Gastroenterol 2002;34:408–415.CrossRefPubMedGoogle Scholar
  84. 84.
    Kjeldsen T, Clausen H, Hirohashi S, Ogawa T, Iijima H, Hakomori S. Preparation and characterization of monoclonal antibodies directed to the tumor-associated O-linked sialosyl-2,6-N acetylgalactosaminyl (sialosyl-Tn) epitope. Cancer Res 1988;48:2214–2220.PubMedGoogle Scholar
  85. 85.
    Takahashi I, Maehara Y, Kusumoto T, Yoshida M, Kakeji Y, Kusumoto H, et al. Predictive value of preoperative serum sialyl Tn antigen levels in prognosis of patients with gastric cancer. Cancer 1993;72:1836–1840.CrossRefPubMedGoogle Scholar
  86. 86.
    Nakagoe T, Sawai T, Tsuji T, Jibiki M, Nanashima A, Yamaguchi H, et al. Pre-operative serum levels of sialyl Tn antigen predict liver metastasis and poor prognosis in patients with gastric cancer. Eur J Surg Oncol 2001;27:731–739.CrossRefPubMedGoogle Scholar
  87. 87.
    Yokoyama H, Ikehara Y, Kodera Y, Ikehara S, Yatabe Y, Mochizuki Y, et al. Molecular basis for sensitivity and acquired resistance to gefitinib in HER2-overexpressing human gastric cancer cell lines derived from liver metastasis. Br J Cancer 2006;95:1504–1513.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2010

Authors and Affiliations

  • Yoshihiro Kakeji
    • 1
  • Masaru Morita
    • 1
  • Yoshihiko Maehara
    • 1
  1. 1.Department of Surgery and Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

Personalised recommendations