Hematogenous tumor cell dissemination during colonoscopy for colorectal cancer

  • M. Koch
  • P. Kienle
  • P. Sauer
  • F. Willeke
  • K. Buhl
  • A. Benner
  • T. Lehnert
  • C. Herfarth
  • M. von Knebel Doeberitz
  • J. WeitzEmail author
Original article


Background: It has long been suspected that mechanical influences may enhance the release of viable colorectal cancer cells into the circulation. The objective of this study was to determine the extent of hematogenous tumor cell spread in colorectal cancer patients during colonoscopy. Methods: Peripheral venous blood samples were taken before and after colonoscopy from 44 patients with colorectal cancer. Blood samples were examined using a reverse-transcriptase polymerase chain reaction assay to amplify cytokeratin 20 transcripts. Results: Eleven patients with colorectal cancer displayed circulating tumor cells before and after colonoscopy (25%), whereas tumor cells were detected in six of 44 patients (14%) only after the procedure (p = 0.03, McNemar’s test: tumor cell detection before after colonoscopy). All control samples consistently tested negative. Conclusions: Mechanical forces may result in enhanced release of viable colorectal cancer cells into the circulation; however, the clinical significance of these results needs to be clarified.


Colorectal cancer Colonoscopy Reverse-trascriptase-polymerase chain reaction Tumor cell dissemination 


  1. 1.
    Agresti, A 1990Categorial data analysis.WileyNew YorkGoogle Scholar
  2. 2.
    Allgayer, H, Heiss, MM, Riesenberg, R,  et al. 1997Urokinase plasminogen activator receptor (uPA-R): one potential characteristic of metastatic phenotypes in minimal residual tumor disease.Cancer Res5713941399PubMedGoogle Scholar
  3. 3.
    Baillie, J 1994Complications of endoscopy.Endoscopy26185203PubMedGoogle Scholar
  4. 4.
    Barnes, JP 1952Physiologic resection of the right colon.Surg Gynecol Obstet94722726PubMedGoogle Scholar
  5. 5.
    Basha, G, Ectors, N, Penninckx, F,  et al. 1997Tumor cell implantation after colonoscopy with biopsies in a patient with rectal cancer.Dis Colon Rectum4015081510PubMedGoogle Scholar
  6. 6.
    Brown, DC, Purushotham, AD, Birnie, GD,  et al. 1995Detection of intraoperative tumor cell dissemination in patients with breast cancer by use of reverse transcription and polymerase chain reaction.Surgery11796101Google Scholar
  7. 7.
    Burchill, SA, Bradbury, MF, Pittman, K,  et al. 1995Detection of epithelial cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction.Br J Cancer71278281Google Scholar
  8. 8.
    Chausovsky, G, Luchansky, M, Figer, A,  et al. 1999Expression of cytokeratin 20 in the blood of patients with disseminated carcinoma of the pancreas, colon, stomach, and the lung.Cancer8623982405CrossRefPubMedGoogle Scholar
  9. 9.
    Eschwege, P, Dumas, F, Blanchet, P,  et al. 1995Hematogenous dissemination of prostatic epithelial cells during radical prostatectomy.Lancet34615281530CrossRefPubMedGoogle Scholar
  10. 10.
    Fleiss, JL 1973Statistical methods for rates and proportions, 2nd edn.WileyNew YorkGoogle Scholar
  11. 11.
    Funaki, NO, Tanaka, J, Itami, A,  et al. 1997Detection of colorectal carcinoma cells in circulating peripheral blood by reverse transcription-polymerase chain reaction targeting cytokeratin-20 mRNA.Life Sci60643652CrossRefPubMedGoogle Scholar
  12. 12.
    Funaki, NO, Tanaka, J, Ohshio, G,  et al. 1998Cytokeratin 20 mRNA in peripheral venous blood of colorectal carcinoma patients.Br J Cancer7713271332Google Scholar
  13. 13.
    Ghossein, R, Bhattacharya, S, Rosai, J 1999Molecular detection of micrometastases and circulating tumor cells in solid tumors.Clin Cancer Res519501960PubMedGoogle Scholar
  14. 14.
    Glaves, D, Huben, RP, Weis, L 1988Haematogenous dissemination of cells from human renal adenocarcinomas.Br J Cancer573235PubMedGoogle Scholar
  15. 15.
    Howard, ML, Greene, FL 1990The effect of preoperative endoscopy on recurrence and survival following surgery for colorectal carcinoma.Am Surg56124127PubMedGoogle Scholar
  16. 16.
    Hu, XC, Chow, LW 2000Fine needle aspiration may shed breast cells into peripheral blood as determined by RT-PCR.Oncology59217222CrossRefPubMedGoogle Scholar
  17. 17.
    Johnson, PWM, Burchill, SA, Selby, PJ 1995The molecular detection of circulating tumor cells.Br J Cancer72268276PubMedGoogle Scholar
  18. 18.
    Jung, R, Petersen, K, Krüger, W,  et al. 1999Detection of micrometastasis by cytokeratin 20 RT-PCR is limited due to stable background transcription in granulocytes.Br J Cancer81870873Google Scholar
  19. 19.
    Koch, M, Weitz, J, Kienle, P,  et al. 2001Comparative analysis of tumor cell dissemination in mesenteric, central and peripheral venous blood in patients with colorectal cancer.Arch Surg1368589PubMedGoogle Scholar
  20. 20.
    Koo, J, Fung, K, Siu, KF,  et al. 1983Recovery of malignant tumor cells from the right atrium during hepatic resection for hepatocellular carcinoma.Cancer5219521956PubMedGoogle Scholar
  21. 21.
    Macfarlane, DE, Dahle, CE 1993Isolating RNA from whole blood—the dawn of RNA-based diagnosis?Nature362186188CrossRefPubMedGoogle Scholar
  22. 22.
    Moll, R, Löwe, A, Laufer, J, Franke, WW 1992Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies.Am J Pathol140427447PubMedGoogle Scholar
  23. 23.
    Moll, R, Zimbelmann, R, Goldschmidt, MD,  et al. 1993The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas.Differentiation537593PubMedGoogle Scholar
  24. 24.
    Moreno, JG, O’Hara, M, Long, JP,  et al. 1997Transrectal ultrasound-guided biopsy causes hematogenous dissemination of prostate cells as determined by RT-PCR.Urology49515520CrossRefPubMedGoogle Scholar
  25. 25.
    Nishizaki, T, Matsumata, T, Kanematsu, T 1990Surgical manipulation of VX2 carcinoma in the rabbit liver evokes enhancement of metastasis.J Surg Res499297PubMedGoogle Scholar
  26. 26.
    Pappalardo, G, Polettini, E, Frattaroli, FM,  et al. 2000Magnetic resonance colonography versus conventional colonoscopy for the detection of colonic endoluminal lesions.Gastroenterology119300304PubMedGoogle Scholar
  27. 27.
    Rex, DK 1998CT and MR colography (virtual colonoscopy): status report.J Clin Gastroenterol27199203CrossRefPubMedGoogle Scholar
  28. 28.
    Scapa, E, Broide, E, Pinhasov, I 1997The effect of colonoscopy on tumor markers.Surg Laparosc Endosc7477479CrossRefPubMedGoogle Scholar
  29. 29.
    So, JB, Alexander, DJ, Chia, YW,  et al. 1997A study of the effects of bowel preparation on CEA levels in patients undergoing surveillance colonoscopy.J R Coll Surg Edinburgh42105106Google Scholar
  30. 30.
    Sobin, LH, Wittekind, C 1997UICC: TNM classification of malignant tumors, 5th edn.WileyLondonGoogle Scholar
  31. 31.
    Soeth, E, Vogel, I, Röder, C,  et al. 1997Comparative analysis of bone marrow and venous blood isolates from gastrointestinal cancer patients for the detection of disseminated tumor cells using reverse transcription PCR.Cancer Res5731063110Google Scholar
  32. 32.
    Sollenberger, LL, Eisenstat, TE, Rubin, RJ,  et al. 1988Is preoperative colonoscopy necessary in carcinoma of the colon and rectum?Am Surg54113115PubMedGoogle Scholar
  33. 33.
    Sträter, J, Wedding, U, Earth, TF,  et al. 1996Rapid onset of apoptosis in vitro follows disruption of β1-integrin/matrix interactions in human colonic crypt cells.Gastroenterology11017761784PubMedGoogle Scholar
  34. 34.
    Turnbull, RB, Kyle, K, Watson, FR,  et al. 1967Cancer of the colon: the influence of the no-touch isolation technique on survival rates.Ann Surg166420425PubMedGoogle Scholar
  35. 35.
    Turner, J, Sturgeon, CM 1993Effect of bowel cleansing and colonoscopy on serum CEA levels.J R Coll Surg Edinburgh388991Google Scholar
  36. 36.
    Weiss, L 1990Metastatic inefficiency.Adv Cancer Res54159211PubMedGoogle Scholar
  37. 37.
    Weitz, J, Kienle, P, Lacroix, J,  et al. 1998Dissemination of tumor cells in patients undergoing surgery for colorectal cancer.Clin Cancer Res4343348PubMedGoogle Scholar
  38. 38.
    Weitz, J, Kienle, P, Magener, A,  et al. 1999Detection of disseminated colorectal cancer cells in lymph nodes, blood and bone marrow.Clin Cancer Res518301836Google Scholar
  39. 39.
    Weitz, J, Koch, M, Kienle, P,  et al. 2000Detection of hematogenous tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer.Ann Surg2326672PubMedGoogle Scholar
  40. 40.
    Wharton, RQ, Jonas, SK, Glover, C,  et al. 1999Increased detection of circulating tumor cells in the blood of colorectal carcinoma patiens using two reverse transcription-PCR and multiple blood samples.Clin Cancer Res541584163Google Scholar
  41. 41.
    Wiggers, T, Jeekel, J, Arends, JW,  et al. 1988No-touch isolation technique in colon cancer: a controlled prospective trial.Br J Surg75409415PubMedGoogle Scholar
  42. 42.
    Willeke, F, Ridder, R, Mechtersheimer, G,  et al. 1998Analysis of FUS-CHOP fusion transcripts in different types of soft tissue liposarcoma and their diagnostic implications.Clin Cancer Res417791884PubMedGoogle Scholar
  43. 43.
    Wyld, DK, Selby, P, Perren, TJ,  et al. 1998Detection of colorectal cancer cells in peripheral blood by reverse-transcriptase polymerase chain reaction for cytokeratin 20.Int J Cancer79288293CrossRefGoogle Scholar
  44. 44.
    Yamaguchi, K, Takagi, Y, Shinichirou, A,  et al. 2000Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection.Ann Surg2325865CrossRefPubMedGoogle Scholar
  45. 45.
    Yuan, J, Coplen, DE, Petros, JA,  et al. 1992Effects of rectal examination, prostatic massage, ultrasonography and needle biopsy on serum prostate specific antigen levels.J Urol147810814PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • M. Koch
    • 1
    • 2
  • P. Kienle
    • 1
    • 2
  • P. Sauer
    • 3
  • F. Willeke
    • 1
    • 2
  • K. Buhl
    • 2
  • A. Benner
    • 4
  • T. Lehnert
    • 2
  • C. Herfarth
    • 1
    • 2
  • M. von Knebel Doeberitz
    • 2
  • J. Weitz
    • 1
    • 2
    Email author
  1. 1.Division for Molecular Diagnostics and Therapy, Department of SurgeryUniversity of Heidelberg, INF 110, D-69120 HeidelbergGermany
  2. 2.Division for Surgical Oncology of the Department of SurgeryUniversity of Heidelberg, INF 110, D-69120 HeidelbergGermany
  3. 3.Department of MedicineUniversity of Heidelberg, INF 110, D-69120 HeidelbergGermany
  4. 4.Central Unit BiostatisticsGerman Cancer Research Center, D-69120 HeidelbergGermany

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