Abstract
Background
Liver resection is the only potential cure for patients with colorectal liver metastasis. However, more than 30% of patients will develop tumour recurrence, probably caused by tumour cells disseminated before or during surgery. As prevention of cell dissemination is barely obtainable, alternative concepts have to be discussed.
Methods
The potential of leukocyte adhesion filters for the removal of cytokeratin positive cells (CK+) from blood was studied in 18 patients undergoing liver resection for colorectal liver metastasis. Blood sampling was done via a liver venous catheter during hepatic mobilisation. Filtration was done with an in-line WBF2 filter system. To define the relation between surgery and cell release we compared patients’ pre-operative and intra-operative blood and bone marrow (BM) samples with their CK expression using immunochemical staining.
Results
CK+ cells were detected in BM samples of nine of 14 patients before surgery, indicating early dissemination. In ten of 18 patients CK+ cells were detected in blood samples during hepatic mobilisation; all ten patients underwent major liver surgery (R0 resection). In those patients recurrent disease was observed more often (P≤0.05). In 17 of 18 patients CK+ cells were not detectable after filtration procedure, which indicated cell adhesion to the filter medium.
Conclusion
Liver resection due to metastasis leads to frequent intra-operative tumour cell shedding. As the detection of CK+ cells is correlated with disease recurrence, modification of surgical techniques to prevent cell dissemination, and additional therapeutic concepts such as advanced filtration technology, have to be discussed.
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References
Turnbull RB Jr, Kyle K, Watson FR, Spratt J (1967) Cancer of the colon: the influence of the no-touch isolation technique on survival rates. Ann Surg 166:420–427
Petrowsky H, Gonen M, Jarnagin W, Lorenz M, DeMatteo R, Heinrich S, et al (2002) Second liver resections are safe and effective treatment for recurrent hepatic metastases from colorectal cancer: a bi-institutional analysis. Ann Surg 235:863–871
Weitz J, Koch M, Kienle P, Schrodel A, Willeke F, Benner A, et al (2000) Detection of hematogenic tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer. Ann Surg 232:66–72
Nishizaki T, Matsumata T, Kanematsu T, Yasunaga C, Sugimachi K (1990) Surgical manipulation of VX2 carcinoma in the rabbit liver evokes enhancement of metastasis. J Surg Res 49:92–97
Fruhauf NR, Dumpich O, Kaudel CP, Kasimir-Bauer S, Oldhafer KJ (2001) Filtration of malignant cells: tumour cell depletion in an ex vivo model using a leukocyte adhesion filter. Perfusion 16 [Suppl]:51–55
Edelman MJ, Potter P, Mahaffey KG, Frink R, Leidich RB (1996) The potential for reintroduction of tumor cells during intraoperative blood salvage: reduction of risk with use of the RC-400 leukocyte depletion filter. Urology 47:179–181
Kainuma M, Fujiwara Y, Kimura N, Shitaokoshi A, Nakashima K, Shimada Y (1991) Monitoring hepatic venous hemoglobin oxygen saturation in patients undergoing liver surgery. Anesthesiology 74:49–52
Fruhauf NR, Oldhafer KJ, Kaiser GM, Kaudel CP, Broelsch CE (2004) Feasibility of veno–venous bypass surgery using leukocyte adhesion filters during abdominal surgery in a porcine model. Eur Surg Res 36:83–87
Nakayama H, Masuda H, Miyake H, Shibata M, Fukuzawa M (2002) Anterior approach for resection of metastatic liver tumors infiltrating the caudate lobe. Hepatogastroenterology 49:1401–1404
Lai EC, Fan ST, Lo CM, Chu KM, Liu CL (1996) Anterior approach for difficult major right hepatectomy. World J Surg 20:314–317; discussion 318
Kasimir-Bauer S, Oberhoff C, Sliwinska K, Neumann R, Schindler AE, Seeber S (2001) Evaluation of different methods for the detection of minimal residual disease in blood and bone marrow of patients with primary breast cancer: importance for clinical use? Breast Cancer Res Treat 69:123–132
Kasimir-Bauer S, Oberhoff C, Schindler AE, Seeber S (2002) A summary of two clinical studies on tumor cell dissemination in primary and metastatic breast cancer: methods, prognostic significance and implication for alternative treatment protocols (review). Int J Oncol 20:1027–1034
Braun S, Muller M, Hepp F, Schlimok G, Riethmuller G, Pantel K (1998) Re: micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst 90:1099–1101
Wagner JS, Adson MA, Van Heerden JA, Adson MH, Ilstrup DM (1984) The natural history of hepatic metastases from colorectal cancer. A comparison with resective treatment. Ann Surg 199:502–508
Weitz J, Kienle P, Lacroix J, Willeke F, Benner A, Lehnert T, et al (1998) Dissemination of tumor cells in patients undergoing surgery for colorectal cancer. Clin Cancer Res 4:343–348
Koch M, Weitz J, Kienle P, Benner A, Willeke F, Lehnert T, et al (2001) Comparative analysis of tumor cell dissemination in mesenteric, central, and peripheral venous blood in patients with colorectal cancer. Arch Surg 136:85–89
Schlimok G, Funke I, Bock B, Schweiberer B, Witte J, Riethmuller G (1990) Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance. J Clin Oncol 8:831–837
Lindemann F, Schlimok G, Dirschedl P, Witte J, Riethmuller G (1992) Prognostic significance of micrometastatic tumour cells in bone marrow of colorectal cancer patients. Lancet 340:685–689
Perseghin P, Vigano M, Rocco G, Della Pona C, Buscemi A, Rizzi A (1997) Effectiveness of leukocyte filters in reducing tumor cell contamination after intraoperative blood salvage in lung cancer patients. Vox Sang 72:221–224
Mayhew E, Glaves D (1984) Quantitation of tumorigenic disseminating and arrested cancer cells. Br J Cancer 50:159–166
Dzik S (1993) Leukodepletion blood filters: filter design and mechanisms of leukocyte removal. Transfus Med Rev 7:65–77
Molnar B, Ladanyi A, Tanko L, Sreter L, Tulassay Z (2001) Circulating tumor cell clusters in the peripheral blood of colorectal cancer patients. Clin Cancer Res 7:4080–4085
Liu CL, Fan ST, Lo CM, Tung-Ping Poon R, Wong J (2000) Anterior approach for major right hepatic resection for large hepatocellular carcinoma. Ann Surg 232:25–31
Oldhafer KJ, Lang H, Schlitt HJ, Hauss J, Raab R, Klempnauer J, et al (2000) Long-term experience after ex situ liver surgery. Surgery 127:520–527
Raab R, Schlitt HJ, Oldhafer KJ, Bornscheuer A, Lang H, Pichlmayr R (2000) Ex-vivo resection techniques in tissue-preserving surgery for liver malignancies. Langenbecks Arch Surg 385:179–184
Acknowledgements
This work was supported by Deutsche Krebshilfe (project 70-2567-OL2). The authors thank Dr. Markus Neuhäuser (Institute of Medical Mathematics, Biometry and Epidemiology of the University of Essen) for supporting the statistical analyses.
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Frühauf, N.R., Kasimir-Bauer, S., Görlinger, K. et al. Peri-operative filtration of disseminated cytokeratin positive cells in patients with colorectal liver metastasis. Langenbecks Arch Surg 390, 15–20 (2005). https://doi.org/10.1007/s00423-004-0518-3
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DOI: https://doi.org/10.1007/s00423-004-0518-3