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Intraoperative molecular detection of circulating tumor cells by reverse transcription-polymerase chain reaction in patients with biliary-pancreatic cancer is associated with hematogenous metastasis

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Abstract

Background

Circulating tumor cells in the blood were frequently detected by reverse transcription-polymerase chain reaction during operation in patients with biliary-pancreatic cancer. We investigated the relationship between circulating tumor cells during operation and hematogenous metastases.

Methods

Blood samples from 67 patients with biliary-pancreatic cancer were obtained from the portal vein, peripheral artery, and superior vena cava during operation. Afer total RNA was extracted from each blood sample, carcinoembryonic antigen (CEA)-specific reverse transcription-polymerase chain reaction was performed.

Results

Intraoperative CEA-messenger RNA (mRNA) expression was detected in the blood of 32 (47.8%) of 67 patients with biliary-pancreatic cancer, although it was not detected in the blood obtained from 20 healthy volunteers or 15 patients with benign disease of the biliary pancreas. The incidence (37.5%) of hematogenous metastases after surgery in the CEA-mRNA-positive group (n =32) was significantly higher than that (11.4%) in the negative group (n=35;P=.01). In stage I, II, and III patients, survival of the CEA-mRNA-positive group was significantly worse compared with that of negative group (P=.03)

Conclusions

Intraoperative molecular detection of circulating tumor cells in patients with biliary-pancreatic cancer relates to a high risk of hematogeneous metastasis and is associated with unfavorable prognosis even after curative resection.

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References

  1. Takao S, Aikou T, Shinchi H, et al. Comparison of relapse and long-term survival between pylorus-preserving and Whipple pancreaticoduodenectomy in periampullary cancer.Am J Surg 1998; 17:467–70.

    Article  Google Scholar 

  2. Takao S, Shinchi, Uchikura K, et al. Liver metastases after curative resection in patients with distal bile duct cancer.Br J Surg 1999; 86:327–31.

    Article  PubMed  CAS  Google Scholar 

  3. Conlon KC, Klimstra DS, Brennan MF, Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinico-pathologic analysis of 5-year survivors.Ann Surg 1996;223:273–9.

    Article  PubMed  CAS  Google Scholar 

  4. Klempnauer J, Ridder GJ, Bektas H, Pichlmay R. Extended reseactions of ductal pancreatic cancer-impact on operative risk and prognosis.Oncology 1996;53:47–53.

    Article  PubMed  CAS  Google Scholar 

  5. Wood DP, Banks ER, Humphreys S, et al. Identification of bone marrow micrometastases in patients with prostate cancer.Cancer 1994;74:2533–40.

    Article  PubMed  Google Scholar 

  6. Jauch KW, Heiss MM, Gruetzner U, et al. Prognostic significance of bone marrow micrometastases in patients with gastric cancer.J Clin Oncol 1996;14:1810–7.

    PubMed  CAS  Google Scholar 

  7. Mor M, Mimori K, Inoue H, et al. Detection of cancer microme-tastases in lymph nodes by reverse transcriptase-polymerase chain reaction.Cancer Res. 1995;55:3417–20.

    Google Scholar 

  8. Schoenfeld A, Luqmani Y, Smith D, et al. Detection of breast cancer micrometastases in axillary lymph nodes by using polymerase chain reaction.Cancer Res 1994;54:2986–90.

    PubMed  CAS  Google Scholar 

  9. Eschwege P, Dumas F, Blanchet P, et al. Haematogenous dissemination of prostatic epithelial cells during radical prostatectomy.Lancet 1995;346:1528–30.

    Article  PubMed  CAS  Google Scholar 

  10. Brown DC, Purushotham AD, Birnie GD, George WD, Detection of intraoperative tumor cell dissemination in patients with breast cancer by use of reverse transcription and polymerase chain reaction.Surgery 1995;117:96–101.

    Article  Google Scholar 

  11. Miyazono F, Takao S, Natsugoe S, et al. Molecular detection of circulating cancer cells during surgery in patients with biliary-pancreatic cancer.Am J Surg 1999;177:475–9.

    Article  PubMed  CAS  Google Scholar 

  12. Miyazono F, Natsugoe S, Takao S, et al. Surgical maneuvers enhance molecular detection of circulating tumor cells during gastric cancer surgery.Ann Surg 2001;233:189–94.

    Article  PubMed  CAS  Google Scholar 

  13. Chomcynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.Anal Biochem 1987;162:156–9.

    Google Scholar 

  14. Gerhard M, Juhl H, Kalthoff H, et al. Specific detection of carcineombryonic antigen-expressing tumor cells in bone marrow aspirates by polymerase chain reaction.J Clin Oncol 1994;12:725–9.

    PubMed  CAS  Google Scholar 

  15. Romsdahl MM, McGrath RG, Hoppe E, McGrew EA. Experimental model for the study of tumor cells in the blood.Acta Cytol 1965;9:141–5.

    PubMed  CAS  Google Scholar 

  16. Liotta LA, Kleinerman J, Saidel GM. Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation.Cancer Res 1974;34:997–1004.

    PubMed  CAS  Google Scholar 

  17. Tyzzer EE, Factors in the production and growth of tumour metastases.J Med Res 1913;28:309–31.

    Google Scholar 

  18. Nishizaki T, Matsumata T, Kanematsu T, et al. Surgical manipulation of VX2 carcinoma in the rabbit liver evokes enhancement of metastasis.J Surg Res 1990;49:92–7.

    Article  PubMed  CAS  Google Scholar 

  19. Mori M, Mimori K, Ueno H, et al. Molecular detection of circulating solid carcinoma cells in the peripheral blood: the concept of early systemic disease.Int J Cancer 1996;68:739–43.

    Article  PubMed  CAS  Google Scholar 

  20. Funaki NO, Tanaka J, Kasamatsu T, et al. Identification of carcinoembryonic antigen mRNA in circulating peripheral blood of pancreatic carcinoma and gastric carcinoma patients.Life Sci 1996; 59:2187–99.

    Article  PubMed  CAS  Google Scholar 

  21. Nomoto S, Nakao A, Kasai Y, et al. Detection of ras gene mutation in perioperative peripheral blood with pancreatic adenocarcinoma.Jpn J Cancer Res 1996;87:793–7.

    PubMed  CAS  Google Scholar 

  22. Matsumura M, Niwa Y, Kato N, et al. Detection of alpha-fetoprotein mRNA, an indicator of hematogeneous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma.Hepatology 1994;20:1418–25.

    Article  PubMed  CAS  Google Scholar 

  23. Gion T, Taketomi A, Shimada M, et al. Perioperative change in albumin messenger RNA levels in patients with hepatocellular carcinoma.Hepatology 1998;28:1663–8.

    Article  PubMed  CAS  Google Scholar 

  24. Tamagawa E, Ueda M, Takahashi S, et al. Pancreatic lymph nodal and plexus micrometastases detected by enriched polymerase chain reaction and nonradioisotopic single-strand conformation polymorphism analysis: a new predictive factor for recurrent pancreatic carcinoma.Clin Cancer Res 1997;3:2143–9.

    PubMed  CAS  Google Scholar 

  25. Kodera Y, Nakanishi H, Yamamura Y, et al. Prognostic value and clinical implications of disseminated cancer cells in the peritoneal cavity detected by reverse transcriptase-polymerase chain reaction and cytology.Int J Cancer 1998;79:429–33.

    Article  PubMed  CAS  Google Scholar 

  26. Soeth E, Vogel I, Roder C, et al. Comparative analysis of bone marrow and venous blood isolates from gastrointestinal cancer patients for the detection of disseminated tumor cells using reverse transcription PCR.Cancer Res 1997;57:3106–10.

    PubMed  CAS  Google Scholar 

  27. Kijima F, Natsugoe S, Takao S et al. Detection and clinical significance of lymph node micrometastasis determined by reverse transcription-polymerase chain reaction in patients with esophageal carcinoma.Oncology 2000;58:38–44.

    Article  PubMed  CAS  Google Scholar 

  28. Nakajo A, Natsugoe S, Ishigami S, et al. Detection and prediction of micrometastasis in the lymph nodes of patients with pN0 gastric cancer.Ann Surg Oncol 2001;8:158–62.

    Article  PubMed  CAS  Google Scholar 

  29. Takao S, Natsugoe S, Aikou T. Hepatic metastasis of gastroenter-ological cancer: its tumor biology and oncological surgery.Hum Cell 1999;12:75–83.

    PubMed  CAS  Google Scholar 

  30. Goydos JS, Brumfield AM, Frezza E, et al. Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma.Ann Surg 1998;227:398–404.

    Article  PubMed  CAS  Google Scholar 

  31. Adler HL, McCurd MA, Kattan MW, et al. Elevated levels of circulating interleukin-6 and transforming growth factor-beta 1 in patients with metastatic prostatic carcinoma.J Urol 1999;161: 182–7.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. First Department of Surgery, Kagoshima University School of Medicine, 8-35-1 Sakuragaoku, 890-8520, Kagoshima, Japan

    Keiichiro Uchikura MD, Sonshin Takao MD, Akihiro Nakajo MD, Futoshi Miyazono MD, Saburou Nakashima MD, Kouki Tokuda MD, Masataka Matsumoto MD, Hiroyuki Shinchi MD, Shoji Natsugoe MD & Takashi Aikou MD

Authors
  1. Keiichiro Uchikura MD
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  2. Sonshin Takao MD
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  3. Akihiro Nakajo MD
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  4. Futoshi Miyazono MD
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  5. Saburou Nakashima MD
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  6. Kouki Tokuda MD
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  7. Masataka Matsumoto MD
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  8. Hiroyuki Shinchi MD
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  9. Shoji Natsugoe MD
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  10. Takashi Aikou MD
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Correspondence to Sonshin Takao MD.

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Uchikura, K., Takao, S., Nakajo, A. et al. Intraoperative molecular detection of circulating tumor cells by reverse transcription-polymerase chain reaction in patients with biliary-pancreatic cancer is associated with hematogenous metastasis. Annals of Surgical Oncology 9, 364–370 (2002). https://doi.org/10.1007/BF02573871

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  • DOI: https://doi.org/10.1007/BF02573871

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