• 第四軍醫(yī)大學西京醫(yī)院肝膽外科(西安710032);

目的　明確外周血微轉移檢測在肝細胞癌 (hepatocellular carcinoma，HCC) 轉移復發(fā)中的診斷價值。方法　通過回顧文獻分析HCC外周血微轉移檢測的方法及意義。 結果　HCC的外周血微轉移檢測目前主要有播散細胞檢測與HCC特異mRNA標記檢測兩類，從理論上來說都被認為是早期檢測轉移復發(fā)的理想方法，但不同實驗研究間普遍存在著相互矛盾的結論，調整改進檢測手段與時間亦未能夠徹底解決檢測結論的沖突。結論 外周血微轉移檢測對于深入理解HCC轉移復發(fā)機理和完善臨床治療有很大意義，但理論與應用中均存在著有待改進的地方，該技術的不斷完善將促進對轉移復發(fā)的機理研究與檢測應用。

引用本文： 李寶定,趙青川,竇科峰. 肝癌外周血微轉移檢測意義及其問題. 中國普外基礎與臨床雜志, 2006, 13(6): 737-740. doi: 復制

版權信息： ?四川大學華西醫(yī)院華西期刊社《中國普外基礎與臨床雜志》版權所有，未經(jīng)授權不得轉載、改編

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2. 　Yamanaka N, Okamoto E, Fujihara S, et al. Do the tumor cells of hepatocellular carcinomas dislodge into the portal venous stream during hepatic resection? [J]. Cancer， 1992; 70(9)∶2263.
3. 　Jeng KS, Sheen IS, Tsai YC. Does the presence of circulating hepatocellular carcinoma cells indicate a risk of recurrence after resection? [J]. Am J Gastroenterol， 2004; 99(8)∶1503.
4. 　Waguri N, Suda T, Nomoto M, et al. Sensitive and specific detection of circulating cancer cells in patients with hepatocellular carcinoma; detection of human telomerase reverse transcriptase messenger RNA after immunomagnetic separation [J]. Clin Cancer Res， 2003; 9(8)∶3004.
5. 　Carr BI. An assay for micrometastatic hepatocellular carcinoma [J]. Gastroenterology， 1994; 106(1)∶264.
6. 　Reid AE, Liang TJ. Tumor marker for metastasis: searching for an abnormal needle in a haystack [J]. Hepatology， 1994; 20(6)∶1631.
7. 　Koo J, Fung K, Siu KF, et al. Recovery of malignant tumor cells from the right atrium during hepatic resection for hepatocellular carcinoma [J]. Cancer， 1983; 52(10)∶1952.
8. 　Leonhardt U, Ritzel U, Ottleben M, et al. Circulating human hepatic lipase mRNA in patients with hepatocellular carcinoma and healthy controls [J]. Eur J Surg， 1999; 165(6)∶539.
9. 　Kar S, Carr BI. Detection of liver cells in peripheral blood of patients with advanced-stage hepatocellular carcinoma [J]. Hepatology， 1995; 21(2)∶403.
10. 　Dodd GD 3rd, Carr BI. Percutaneous biopsy of portal vein th-rombus: a new staging technique for hepatocellular carcinoma [J]. AJR Am J Roentgenol， 1993; 161(2)∶229.
11. 　Vilana R, Bru C, Bruix J, et al. Fine-needle aspiration biopsy of portal vein thrombus: value in detecting malignant thrombosis [J]. AJR Am J Roentgenol， 1993; 160(6)∶1285.
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13. 　Wong IH, Lo YM, Yeo W, et al. Frequent p15 promoter me-thylation in tumor and peripheral blood from hepatocellular carcinoma patients [J]. Clin Cancer Res， 2000; 6(9)∶3516.
14. 　Komeda T, Fukuda Y, Sando T, et al. Sensitive detection of circulating hepatocellular carcinoma cells in peripheral venous blood [J]. Cancer， 1995; 75(9)∶2214.
15. 　Sabile A, Louha M, Bonte E, et al. Efficiency of Ber-EP4 antibody for isolating circulating epithelial tumor cells before RT-PCR detection [J]. Am J Clin Pathol， 1999; 112(2)∶171.
16. 　Vona G, Sabile A, Louha M, et al. Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulatingtumor cells [J]. Am J Pathol， 2000; 156(1)∶57.
17. 　Rostagno P, Moll JL, Bisconte JC, et al. Detection of rare circulating breast cancer cells by filtration cytometry and identification by DNA content: sensitivity in an experimental model [J]. Anticancer Res， 1997; 17(4A)∶2481.
18. 　Ito A, Shinkai M, Honda H, et al. Medical application of functionalized magnetic nanoparticles [J]. J Biosci Bioengin, 2005; 100(1)∶1.
19. 　Jiang SY, Shyu RY, Huang MF, et al. Detection of alphafetoprotein-expressing cells in the blood of patients with hepatoma and hepatitis [J]. Br J Cancer， 1997; 75(6)∶928.
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27. 　Matsumura M, Niwa Y, Kato N, et al. Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma [J]. Hepatology， 1994; 20(6)∶1418.
28. 　Miyamoto A, Fujiwara Y, Sakon M, et al. Development of a multiple-marker RT-PCR assay for detection of micrometastases of hepatocellular carcinoma [J]. Dig Dis Sci， 2000; 45(7)∶1376.
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32. 　Nicoli N, Casaril A, Hilal MA, et al. A case of rapid intrahepatic dissemination of hepatocellular carcinoma after radiofrequency thermal ablation [J]. Am J Surg， 2004; 188(2)∶165.
33. 　Wu F, Wang ZB, Jin CB, et al. Circulating tumor cells in patients with solid malignancy treated by high-intensity focused ultrasound [J]. Ultrasound Med Biol， 2004; 30(4)∶511.
  1. 1. 　Tang ZY, Ye SL, Liu YK, et al. A decade’s studies on metastasis of hepatocellular carcinoma [J]. J Cancer Res Clin Oncol， 2004; 130(4)∶187.
  2. 2. 　Yamanaka N, Okamoto E, Fujihara S, et al. Do the tumor cells of hepatocellular carcinomas dislodge into the portal venous stream during hepatic resection? [J]. Cancer， 1992; 70(9)∶2263.
  3. 3. 　Jeng KS, Sheen IS, Tsai YC. Does the presence of circulating hepatocellular carcinoma cells indicate a risk of recurrence after resection? [J]. Am J Gastroenterol， 2004; 99(8)∶1503.
  4. 4. 　Waguri N, Suda T, Nomoto M, et al. Sensitive and specific detection of circulating cancer cells in patients with hepatocellular carcinoma; detection of human telomerase reverse transcriptase messenger RNA after immunomagnetic separation [J]. Clin Cancer Res， 2003; 9(8)∶3004.
  5. 5. 　Carr BI. An assay for micrometastatic hepatocellular carcinoma [J]. Gastroenterology， 1994; 106(1)∶264.
  6. 6. 　Reid AE, Liang TJ. Tumor marker for metastasis: searching for an abnormal needle in a haystack [J]. Hepatology， 1994; 20(6)∶1631.
  7. 7. 　Koo J, Fung K, Siu KF, et al. Recovery of malignant tumor cells from the right atrium during hepatic resection for hepatocellular carcinoma [J]. Cancer， 1983; 52(10)∶1952.
  8. 8. 　Leonhardt U, Ritzel U, Ottleben M, et al. Circulating human hepatic lipase mRNA in patients with hepatocellular carcinoma and healthy controls [J]. Eur J Surg， 1999; 165(6)∶539.
  9. 9. 　Kar S, Carr BI. Detection of liver cells in peripheral blood of patients with advanced-stage hepatocellular carcinoma [J]. Hepatology， 1995; 21(2)∶403.
  10. 10. 　Dodd GD 3rd, Carr BI. Percutaneous biopsy of portal vein th-rombus: a new staging technique for hepatocellular carcinoma [J]. AJR Am J Roentgenol， 1993; 161(2)∶229.
  11. 11. 　Vilana R, Bru C, Bruix J, et al. Fine-needle aspiration biopsy of portal vein thrombus: value in detecting malignant thrombosis [J]. AJR Am J Roentgenol， 1993; 160(6)∶1285.
  12. 12. 　Fujimoto K, Nakamura K, Takashima S, et al. Angioscopy of the inferior vena cava: preliminary observations in cases with involvement by neoplasm. Work in progress [J]. J Vasc Interv Radiol， 1991; 2(3)∶371.
  13. 13. 　Wong IH, Lo YM, Yeo W, et al. Frequent p15 promoter me-thylation in tumor and peripheral blood from hepatocellular carcinoma patients [J]. Clin Cancer Res， 2000; 6(9)∶3516.
  14. 14. 　Komeda T, Fukuda Y, Sando T, et al. Sensitive detection of circulating hepatocellular carcinoma cells in peripheral venous blood [J]. Cancer， 1995; 75(9)∶2214.
  15. 15. 　Sabile A, Louha M, Bonte E, et al. Efficiency of Ber-EP4 antibody for isolating circulating epithelial tumor cells before RT-PCR detection [J]. Am J Clin Pathol， 1999; 112(2)∶171.
  16. 16. 　Vona G, Sabile A, Louha M, et al. Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulatingtumor cells [J]. Am J Pathol， 2000; 156(1)∶57.
  17. 17. 　Rostagno P, Moll JL, Bisconte JC, et al. Detection of rare circulating breast cancer cells by filtration cytometry and identification by DNA content: sensitivity in an experimental model [J]. Anticancer Res， 1997; 17(4A)∶2481.
  18. 18. 　Ito A, Shinkai M, Honda H, et al. Medical application of functionalized magnetic nanoparticles [J]. J Biosci Bioengin, 2005; 100(1)∶1.
  19. 19. 　Jiang SY, Shyu RY, Huang MF, et al. Detection of alphafetoprotein-expressing cells in the blood of patients with hepatoma and hepatitis [J]. Br J Cancer， 1997; 75(6)∶928.
  20. 20. 　Funaki N, Tanaka J, Seto S, et al. Highly-sensitive identification of alpha-fetoprotein mRNA in circulating peripheral blood of hepatocellular carcinoma patients [J]. Life Sci， 1995; 57(17)∶1621.
  21. 21. 　Matsumura M, Niwa Y, Hikiba Y, et al. Sensitive assay for detection of hepatocellular carcinoma associated gene transcription (alpha-fetoprotein mRNA) in blood [J]. Biochem Biophys Res Commun， 1995; 207(2)∶813.
  22. 22. 　Chou HC, Sheu JC, Huang GT, et al. Albumin messenger RNA is not specific for circulating hepatoma cells [J]. Gastroenterology， 1994; 107(2)∶630.
  23. 23. 　Kienle P, Weitz J, Klaes R, et al. Detection of isolated disseminated tumor cells in bone marrow and blood samples of patients with hepatocellular carcinoma [J]. Arch Surg， 2000; 135(2)∶213.
  24. 24. 　Gross-Goupil M, Saffroy R, Azoulay D, et al. Real-time quantification of AFP mRNA to assess hematogenous dissemination after transarterial chemoembolization of hepatocellular carcinoma [J]. Ann Surg， 2003; 238(2)∶241.
  25. 25. 　Mou DC, Cai SL, Peng JR, et al. Evaluation of MAGE-1 and MAGE-3 as tumour-specific markers to detect blood dissemination of hepatocellular carcinoma cells [J]. Br J Cancer， 2002; 86(1)∶110.
  26. 26. 　Fujiwara Y, Sugita Y, Nakamori S, et al. Assessment of Stanniocalcin-1 mRNA as a molecular marker for micrometastases of various human cancers [J]. Int J Oncol， 2000; 16(4)∶799.
  27. 27. 　Matsumura M, Niwa Y, Kato N, et al. Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma [J]. Hepatology， 1994; 20(6)∶1418.
  28. 28. 　Miyamoto A, Fujiwara Y, Sakon M, et al. Development of a multiple-marker RT-PCR assay for detection of micrometastases of hepatocellular carcinoma [J]. Dig Dis Sci， 2000; 45(7)∶1376.
  29. 29. 　Wong IH, Yeo W, Leung T, et al. Circulating tumor cell mRNAs in peripheral blood from hepatocellular carcinoma patients under radiotherapy, surgical resection or chemotherapy: a quantitative evaluation [J]. Cancer Lett， 2001; 167(2)∶183.
  30. 30. 　Chelly J, Concordet JP, Kaplan JC, et al. Illegitimate transcription: transcription of any gene in any cell type [J]. Proc Natl Acad Sci USA， 1989; 86(8)∶2617.
  31. 31. 　Aselmann H, Wolfes H, Rohde F, et al. Quantification of alpha 1-fetoprotein mRNA in peripheral blood and bone marrow: a tool for perioperative evaluation of patients with hepatocellular carcinoma [J]. Langenbecks Arch Surg， 2001; 386(2)∶118.
  32. 32. 　Nicoli N, Casaril A, Hilal MA, et al. A case of rapid intrahepatic dissemination of hepatocellular carcinoma after radiofrequency thermal ablation [J]. Am J Surg， 2004; 188(2)∶165.
  33. 33. 　Wu F, Wang ZB, Jin CB, et al. Circulating tumor cells in patients with solid malignancy treated by high-intensity focused ultrasound [J]. Ultrasound Med Biol， 2004; 30(4)∶511.