#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Detection of Minimal Residual Disease and its Significance for Eestablishing Prognoses in Patients with Laparoscopic Resections of Colorectal Carcinomas


Authors: M. Škrovina;  M. Duda;  J. Srovnal *;  Bartoš J. Radová L. *;  M. Hajdúch *;  R. Soumarová **
Authors‘ workplace: Chirurgické oddělení, Nemocnice s poliklinikou a Komplexní onkologické centrum J. G. Mendela v Novém Jičíně, primář: MUDr. Matej Škrovina ;  Laboratoř experimentální medicíny, Lékařská fakulta UP v Olomouci, primář: doc. MUDr. Marián Hajdúch, Ph. D. *;  Radioterapie a. s., Komplexní onkologické centrum J. G. Mendela v Novém Jičíně, primář: doc. MUDr. Renata Soumarová, Ph. D. **
Published in: Rozhl. Chir., 2010, roč. 89, č. 6, s. 362-369.
Category: Monothematic special - Original

Overview

Aim:
The aim of the study was to detect minimal residual disease (MRD) in bone marrow samples, portal and peripheral blood samples collected from colorectal carcinoma (CRC) patients, and to assess the results in relation with clinical stages of the disorder and to evaluate potential correlation between the MRD presence and the disease relapse and overall patient survival rates.

Material and Methods:
The study included patients with primary CRCs indicated for laparoscopic resections. From September 21, 2006 to December 31, 2008, the authors selected 159 subjects with median age of 56. 126 patients (79.25%) were operated for CRC stage I-III, 33 patients (20.75%) had CRC stage IV. Six samples were collected in each subject to detect the MRD presence (systemic venous blood and bone marrow at the beginning of the procedure, venous blood from the mesenteric bed, systemic venous blood after the resection procedure, systemic venous blood and bone marrow one month after the procedure), as well as samples of the tumor tissue. Real-time RT-PCR method was use to detect the MRD.

Results:
The study confirmed correlation between MRD positivity in preoperative bone marrow samples and the disease stage (p < 0.035). It showed correlation between findings in preoperatively collected systemic venous blood samples and in mesenteric venous blood samples (p < 0.003), correlation between findings in systemic venous blood samples collected after the resections procedures and in systemic venous blood samples one month after the procedure (p < 0.015), as well as correlation between findings in preoperative systemic venous blood samples and findings in systemic venous blood samples collected after the procedures (p < 10-5). The authors found out that the surgical procedure affected the MRD presence in systemic venous blood samples in primary negative patients (p < 0.025). During the study period, the authors revealed no statistically significant correlation between the MRD findings in stage I-III patients and their disease-free survival (p < 0.59). Considering the above results, possible direct correlation between positive MRD findings in systemic venous blood samples, which were collected preoperatively in CRC stage I-III patients, and reduced survival time is expected (p < 0.075). During the study period, the overall survival time was significantly reduced in stage I-III patients with positive findings in postoperative systemic venous blood samples, compared to that in negative patients (p < 0.004).

Conclusion:
The data suggest certain correlations between the MRD findings and the disease prognosis. The authors continue to collect further samples and assess the outcomes in order to enlarge the patient study group and the data, and plan to evaluate the outcomes in a 5-year to 10- year follow up period.

Key words:
minimal residual disease – colorectal carcinoma – laparoscopic resection


Sources

1. International Union Against Cancer (UICC), TNM klasifikace zhoubných novotvaru, Šesté vydání 2002, Ústav zdravotníckých informací a statistiky České republiky, Praha, 2004, 65–68, ISBN 80-7280-391-3.

2. Tsavellas, G., Huang, A., McCullough, T., Patel, H., Araia, R., Allen-Mersh, T. G. Flow cytometry correlates with RT-PCR for detection of spiked but not circulating colorectal cancer cells. Clin. Exp. Metastasis, 2002; 19: 495–502.

3. Tsavellas, G., Patel, H., Allen-Mersh, T. G. Detection and clinical significance of occult tumour cells in colorectal cancer. Br. J. Surg., 2001; 88: 1307–1320.

4. Smith, B. M., Slade, M. J., English, J., et al. Response of circulating tumor cells to systematic therapy in patients with metastatic breast cancer: Comparison of quantitave polymerase chain reaction and immunocytochemical techniques. Journal of Clinical Oncology, 2000; 18: 1432–1439.

5. Gerhard, M., Juhl, H, Kalthoff, H., Schreiber, H. W., Wagener, C., Neumaier, M. Specific detection of carcinoembryonic antigen-expressing tumor cells in bone marrow aspirates by polymerase chain reaction. J. Clin. Oncol., 2001; 12: 725–729.

6. Wong, I. H. N., Yeo, W., Chan, A. T., Johnson, P. J. Quantitaive relationship of the circulating tumor burden assessed by reverse transcription-polymerase chain reaction for cytokeratin 19 mRNA in peripheral blood of colorectal cancer patients with Dukes‘ stage, serum carcinoembryonic antigen level and tumor progression. Cancer Letters, 2001; 162: 65–73.

7. Vlems, F. A., Diepstra, J. H. S., Cornelissen, I. M. H. A., Ruers, T. J. M., Ligtenberg, M. J. L., Punt, C. J. A., van Krieken, J. H. J. M., Wobbes, Th., van Muijen, G. N. P. Limitations of cytokeratin 20 RT-PCR to detect disseminated tumour cells in blood und bone marrow of patients with colorectal cancer: expression in controls and downregulation in tumour tissue. J. Clin. Pathol.: Mol. Pathol., 2002; 55: 156–163.

8. Chen, W. S., Chung, M. Y., Liu, J. H., Liu, J. M., Lin, J. K. Impact of circulating free tumor cells in the peripheral blood of colorectal cancer patients during laparoscopic surgery. World J. Surg., 2004; 28: 552–557.

9. Hardingham, J. E., Kotasek, D., Farmer, B., Butler, R. N., Mi, J. X., Sage, R. E., Dobrovic, A. Imunobead-PCR: a technique for the detection of circulating tumor cells using immunomagnetic beads and the polymerase chain reaction. Cancer Res., 1993; 53: 3455–3458.

10. Fidler, I. J. Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res., 1990; 50: 6130–6138.

11. Patel, H., Le Marer, N., Wharton, R. Q., Khan, Z. A., Araia, R., Glover, C., Henry, M. M., Allen-Mersh, T. G. Clearance of circulating tumor cells after excision of primare colorectal cancer. Ann. Surg., 2002; 235: 226–231.

12. Ito, S., Nakanishi, H., Hirai, T., Kato, T., Kodera, Y., Feng, Z., Kasai, Y., Ito, K., Akiyama, S., Nakao, A., Tatematsu, M. Quanatitative detection of CEA expressing free tumor cells in the peripheral blood of colorectal cancer patients during surgery with real-time RT-PCR on a LightCycler. Cancer Letters, 2002; 183: 195–203.

13. Wang, J. Y., Wu, C. H., Lu, C. Y., Hsieh, J. S., Wu, D. C., Huang, S. Y., Lin, S. R. Molecular detection of circulating tumor cells in the peripheral blood of patients with colorectal cancer using RT-PCR: significance of the prediction of postoperative metastasis. World J. Surg., 2006; 30: 1007–1013.

14. Feezor, R. J., Copeland, E. M., Hochwald, S. N. Significance of micrometastases in colorectal cancer. Ann. Surg. Oncol., 2002; 9: 944–953.

15. Yamaguchi, K., Takagi, Y., Aoki, S., Futamura, M., Saji, S. Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Ann. Surg., 2000; 232: 58–65.

16. Sadahiro, S., Suzuki, T., Tokunaga, N., Yurimoto, S., Yasuda, S., Tajima, T., Makuuchi, H., Murayama, C., Matsuda, K. Detection of tumor cells in the portal and peripheral blood of patients with colorectal carcinoma using competetive reverse transcriptase-polymerase chain reaction. Cancer, 2001; 92: 1251–1258.

17. Taniguchi, T., Makino, M., Suzuki, K., Kaibara, N. Prognostic significance of reverse transcriptase-polymerase chain reaction measurement of carcinoembryonic antigen mRNA levels in tumor drainage blood and peripheral blood of patients with colorectal carcinoma. Cancer, 2000; 89: 970–976.

18. Iinuma, H., Okinaga, K., Egami, H., Mimori, K., Hayashi, N., Nishida, K., Adachi, M., Mori, M., Sasako, M. Usefulness and clinical significance of quantitative real-time RT-PCR to detect isolated tumor cells in the peripheral blood and tumor drainage blood of patients with colorectal cancer. Int. J. Oncol., 2006; 28: 297–306.

19. Lindemann, F., Schlimok, G., Dirschedl, P., Witte, J., Riethmuller, G. Prognostic significance of micrometastatic tumor cells in bone marrow of colorectal cancer patients. Lancet, 1992; 340: 685–689.

20. Flatmark, K., Bjornland, K., Johannessen, H. O., Hegstad, E., Rosales, R., Harklau, L., Solhauq, J. H., Faye, R. S., Soreide, O., Fodstad, O. Study Group for Micrometastases in BM in Colorectal Cancer. Immunomagnetic detection of micrometastatic cells in bone marrow of colorectal cancer patients. Clin. Cancer Res., 2002; 8: 444–449.

Labels
Surgery Orthopaedics Trauma surgery
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#