Strategies for Synchronous and Multiple Metastatic Liver Tumors Designed from Epithelial-Mesenchymal Transition Concept

Abstract

At some point in the natural course of colorectal cancer up to 50% of patients will develop metastasis to the liver and it is one of the most critical effects for patient prognosis. The incidence of synchronous liver metastasis has been detected at around 20% - 25%, but the optimal timing of surgical resection remains controversial. Neoadjuvant chemotherapy has also been found to be beneficial not only for initially unresectable but also resectable synchronous metastases. Then, traditional surgical strategies of hepatic resection in accordance with past chemotherapeutic regimens have been used decreasingly over the past several years. This review will primarily discuss treatments in association with the recent developed chemotherapeutic regimens and surgical procedure from the clinical data and the concept for epithetlial-mesenchymal transition, which has recently been studied to elucidate mechanisms of the liver metastatic process.

Share and Cite:

S. Osada, H. Imai, Y. Sasaki and K. Yoshida, "Strategies for Synchronous and Multiple Metastatic Liver Tumors Designed from Epithelial-Mesenchymal Transition Concept," Journal of Cancer Therapy, Vol. 3 No. 3, 2012, pp. 201-206. doi: 10.4236/jct.2012.33029.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] R. Lochan, S. A. White and D. M. Manas, “Liver Resection for Colorectal Liver Metastasis,” Surgical Oncology, Vol. 16, No. 1, 2007, pp. 33-45. doi:10.1016/j.suronc.2007.04.010
[2] National Institute for Health and Clinical Excellence, “Improving Outcomes in Colorectal Cancers,” June 23, 2004.
[3] Y. Sakamoto, S. Fujita, T. Akasu, S. Nara, M. Esaki, K. Shimada, S. Yamamoto, Y. Moriya and T. Kosuge, “Is surgical Resection Justified for Stage IV Colorectal Cancer Patients Having Bilobar Hepatic Metastasis?—An Analysis of Survival of 77 Patients Undergoing Hepatectomy,” Journal of Surgical Oncology, Vol. 102, No. 7, 2010, pp. 784-788. doi:10.1002/jso.21721
[4] S. Matsui, S. Osada, H. Tomita, et al., “Clinical Significance of Aggressive Hepatectomy for Colorectal Liver Metastasis, Evaluated from the HGF/c-Met Pathway,” International Journal of Oncology, Vol. 37, No. 2, 2010, pp. 289-297.
[5] R. C. Bates and A. M. Mercurio, “The Epithelial-Mesenchymal Transition (EMT) and Colorectal Cancer Progression,” Cancer Biology & Therapy, Vol. 4, No. 4, 2005, pp. 365-370. doi:10.4161/cbt.4.4.1655
[6] H. Y. Chang, M. C. Kao, T. D. Way, C. T. Ho and E. Fu, “Diosgenin Suppresses Hepatocyte Growth Factor (HGF)-Induced Epithelial-Mesenchymal Transition by Down-Regulation of Mdm2 and Vimentin,” Journal of Agricultural and Food Chemistry, Vol. 59, No. 10, 2011, pp. 5357-5363.
[7] B. Nordlinger, H. Sorbye, B. Glimelius, et al., “Perioperative Chemotherapy with FOLFOX4 and Surgery Versus Surgery Alone for Resectable Liver Metastases from Colorectal Cancer (EORTC Intergroup Trial 40983): A Randomised Controlled Trial,” The Lancet, Vol. 371, No. 9617, 2008, pp. 1007-1016. doi:10.1016/S0140-6736(08)60455-9
[8] R. Adam, G. Pascal, D. Castaing, et al., “Tumor Progression While on Chemotherapy: A Contraindication to Liver Resection for Multiple Colorectal Metastases?” Annals of Surgery, Vol. 240, No. 6, 2004, pp. 1052-1064. doi:10.1097/01.sla.0000145964.08365.01
[9] A Falcone, S Ricci, I Brunetti, et al., “Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin and Irinotecan (FOLFOXIRI) Compared with Infusional Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) as First-Line Treatment for Metastatic Colorectal Cancer,” Journal of Clinical Oncology, Vol. 25, No. 13, 2007, pp. 1670-1676. doi:10.1200/JCO.2006.09.0928
[10] M. Ychou, F. Viret, A. Kramar, F. Desseigne, E. Mitry, et al., “A Tritherapy with Fluorouracil/Leucovorin, Irinotecan and Oxaliplatin, FOLFILINOX, a Phase II Study in Colorectal Cancer Patients with Unresectable Liver Metastases,” Cancer Chemotherapy and Pharmacology, Vol. 62, No. 2, 2008, pp. 195-201. doi:10.1007/s00280-007-0588-3
[11] S. Osada, Y. Sanada, Y. Tanaka, A. Ikawa, Y. Tokuyama, N. Okumura, K. Nonaka, T. Takahashi, K. Yamaguchi and K. Yoshida, “Strategy for Synchronous and Multiple Liver Metastasis,” Hepato-Gastroenterology, Vol. 59, No. 113, 2012, pp. 198-203.
[12] A. Brouquet, M. M. Mortenson, J. N. Vauthey, M. A. Rodriguez-Bigas, M. J. Overman, G. J. Chang, S. Kopetz, C. Garrett, S. A. Curley and E. K. Abdalla, “Surgical Strategies for Synchronous Colorectal Liver Metastases in 156 Consecutive Patients: Classic, Combined or Reverse Strategy?” Journal of the American College of Surgeons, Vol. 210, No. 6, 2010, pp. 934-941. doi:10.1016/j.jamcollsurg.2010.02.039
[13] S. K. Reddy, T. M. Pawlik, D. Zorzi, et al., “Simultaneous Resection of Colorectal Cancer and Synchronous Liver Metastases: A Multi-Institutional Analysis,” Annals of Surgical Oncology, Vol. 14, No. 12, 2007, pp. 4481-4491. doi:10.1245/s10434-007-9522-5
[14] S. J. Moug, D. Smith, E. Leen, C. Roxburgh and P. G. Horgan, “Evidence for a Synchronous Operative Approach in the Treatment of Colorectal Cancer with Hepatic Metastasis: A Case Matched Study,” European Journal of Surgical Oncology, Vol. 36, No. 4, 2010, pp. 365-370. doi:10.1016/j.ejso.2009.11.007
[15] J. Chen, Q. Li, C. Wang, H. Zhu, Y. Shi and G. Zhao, “Simultaneous vs. Staged Resection for Synchronous Colorectal Liver Metastases: A Meta-Analysis,” International Journal of Colorectal Disease, Vol. 26, No. 2, 2011, pp. 191-199. doi:10.1007/s00384-010-1018-2
[16] J. G. Hillingso and P. Wille-Jorgensen, “Staged or Simultaneous Resection of Synchronous Liver Metastases from Colorectal Cancer: A Systematic Review,” Colorectal Disease, Vol. 11, No. 1, 2009, pp. 3-10. doi:10.1111/j.1463-1318.2008.01625.x
[17] H. Sorbye, M. Mauer, T. Gruenberger, B. Glimelius, G. J. Poston, P. M. Schlag, P. Rougier, W. O. Bechstein, J. N. Primrose, E. T. Walpole, M. Finch-Jones, D. Jaeck, D. Miza, R. W. Parks, L. Collette, E. V. Cutsem, W. Scheithauer, M. P. Lutz and B. Nordlinger, “Predictive Factors for the Benefit of Perioperative FOLFOX for Resectable Liver Metastasis in Colorectal Cancer Patients (EORTC Intergroup Trial 40983),” Annals of Surgery, Vol. 255, No. 3, 2012, pp. 534-539. doi:10.1097/SLA.0b013e3182456aa2
[18] L. Spelt, B. Andersson, J. Nilsson and R. Andersson, “Prognostic Models for Outcome following Liver Resection for Colorectal Cancer Metastases: A Systematic Review,” European Journal of Surgical Oncology, Vol. 38, No. 1, 2012, pp. 16-24. doi:10.1016/j.ejso.2011.10.013
[19] R. J. De Haas, D. A. Wicherts and R. Adam, “Resection of Colorectal Liver Metastases with Extrahepatic Diseases,” Digestive Surgery, Vol. 25, No. 6, 2009, pp. 461-466. doi:10.1159/000184737
[20] G. Msai, F. Loupakis, L. Pollina, E. Vasile, S. Cupini, S. Ricci, I. M. Brunetti, R. Ferraldeschi, G. Naso, F. Filipponi, M. Andreuccetti and A. Falcone, “Long-Term Outcome of Initially Unresectable Metastatic Colorectal Cancer Patients Treated with 5-Fluorouracil/Ieucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Followed by Radical Surgery of Metastases,” Annals of Surgery, Vol. 249, No. 3, 2009, pp. 420-425. doi:10.1097/SLA.0b013e31819a0486
[21] T. M. Pawlik, K. Olino, A. L. Gleisner, M. Torbenson, et al., “Preoperative Chemotherapy for Colorectal Liver Metastases: Impact on Hepatic Histology and Postoperative Outcome,” Journal of Gastrointestinal Surgery, Vol. 11, No. 7, 2007, pp. 863-868. doi:10.1007/s11605-007-0149-4
[22] D. Zorzi, A. Laurent, T. M. Pawlik, G. Y. Laumes, J. N. Vauthey and E. K. Abdalla, “Chemotherapy-Associated Hepatotoxicity and Surgery for Colorectal Liver Metastases,” British Journal of Surgery, Vol. 97, No. 3, 2007, pp. 274-286. doi:10.1002/bjs.5719
[23] R. Adam, G. Pascal, D. Azoulay, K. Tanaka, D. Castaing and H. Bismuth, “Liver Resection for Colorectal Metastases, the Third Hepatectomy,” Annals of Surgery, Vol. 238, No. 6, 2003, pp. 871-884. doi:10.1097/01.sla.0000098112.04758.4e
[24] B. S. Langenhoff, P. F. M. Krabbe and T. J. M. Ruers, “Efficacy of Follow-Up after Surgical Treatment of Colorectal Liver Metastases,” European Journal of Surgical Oncology, Vol. 35, No. 2, 2009, pp. 180-186.
[25] K. Tanaka, H. Shimada, K. Matsuo, et al., “Outcome after Simultaneous Colorectal and Hepatic Resection for Colorectal Cancer with Synchronous Metastases,” Surgery, Vol. 136, No. 3, 2004, pp. 650-659. doi:10.1016/j.surg.2004.02.012
[26] A. Antonion, R. E. Lovegrove, H. S. Tilney, et al., “Meta Analysis of Clinical Outcome after First and Second Liver Resection for Colorectal Metastases,” Surgery, Vol. 141, No. 1, 2007, pp. 9-18. doi:10.1016/j.surg.2006.07.045
[27] G. Mentha, P. E. Majno, A. Andres, et al., “Neoadjuvant Chemotherapy and Resection of Advanced Synchronous Liver Metastases before Treatment of the Colorectal Primary,” British Journal of Surgery, Vol. 93, No. 7, 2006, pp. 872-878. doi:10.1002/bjs.5346
[28] A. Brouquet, M. M. Mortenson, J. N. Vauthey, M. A. Rodriguez-Bigas, M. J. Overman, G. J. Chang, S. Kopetz, G. Christopher, S. A. Curley and E. K. Abdalla, “Surgical Strategies for Synchronous Colorectal Liver Metastases in 156 Consecutive Patients: Calssic, Combined or Reverse Strategy?” Journal of the American College of Surgeons, Vol. 210, No. 6, 2010, pp. 934-941. doi:10.1016/j.jamcollsurg.2010.02.039
[29] G. Mentha, A. D. Roth, S. Terraz, P. Giostra, A. Andres, P. Morel, L. Rubbia-Brandt and P. E. Majno, “‘Liver First’ Approach in the Treatment of Colorectal Cancer with Synchronous Liver Metastases,” Digestive Surgery, Vol. 25, No. 6, 2008, pp. 430-435. doi:10.1159/000184734
[30] M. Karoui, W. Koubaa, C. Delbaldo, et al., “Chemotherapy Has Also an Effect on Primary Tumor in Colon Carcinoma,” Annals of Surgical Oncology, Vol. 15, No. 12, 2008, pp. 3440-3446. doi:10.1245/s10434-008-0167-9
[31] J. M. Lee, S. Dedhar, R. Kalluri and E. W. Thompson, “The Epithelial-Mesenchymal Transition: New Insights in Signaling, Development, and Disease,” The Journal of Cell Biology, Vol. 172, No. 7, 2006, pp. 973-981. doi:10.1083/jcb.200601018
[32] E. Vincan and N. Barker, “The Upstream Components of the Wnt Signalling Pathway in the Dynamic EMT and MET Associated with Colorectal Cancer Progression,” Clinical and Experimental Metastasis, Vol. 25, No. 6, 2008, pp. 657-663. doi:10.1007/s10585-008-9156-4
[33] S. Osada, M. Kanematsu, H. Imai, S. Goshima and Y. Sugiyama, “Evaluation of Extracellular Signal Regulated Kinase Expression and Its Relation to Treatment of Hepatocellular Carcinoma,” Journal of the American College of Surgeons, Vol. 201, No. 3, 2005, pp. 405-411. doi:10.1016/j.jamcollsurg.2005.05.015
[34] T. Tanahashi, S. Osada, A. Yamada, J. Kato, K. Yawata, H. Imai, Y. Sasaki, S. Saito, Y. Tanaka, K. Nonaka and K. Yoshida, “Extracellular Signal-Regulated Kinase and Akt Activation Play a Critical Role in the Process of Hepatocyte Growth Factor-Induced Epithelial-Mesenchymal Transition,” Cancer, 2012, in press.
[35] Y. Wu and B. P. Zhou, “New Insights of Epithelial-Mesenchymal Transition in Cancer Metastasis,” Acta Biochimica et Biophysica Sinica, Vol. 40, No. 7, 2008, pp. 643-650. doi:10.1111/j.1745-7270.2008.00443.x
[36] L. A. Walsh and S. Damjanovski, “IGF-1 Increases Invasive Potential of MCF 7 Breast Cancer Cells and Induces Activation of Latent TGF-Beta1 Resulting in Epithelial to Mesenchymal Transition,” Cell Communication and Signaling, Vol. 9, 2011, p. 10. doi:10.1186/1478-811X-9-10
[37] T. Nakamura, Y. Kato, H. Fuji, T. Horiuchi, Y. Chiba and K. Tanaka, “E-Cadherin-Dependent Intercellular Adhesion Enhances Chemoresistance,” International Journal of Molecular Medicine, Vol. 12, No. 5, 2003, pp. 693-700.
[38] S. J. Yu, J. K. Yu, W. T. Ge, H. G. Hu, Y. Yuan and S. Zheng, “SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are Prognosis-Related in Colorectal Cancer,” World Journal of Gastroenterology, Vol. 17, No. 5, 2011, pp. 2028-2036. doi:10.3748/wjg.v17.i15.2028
[39] S. Osada, H. Imai, Y. Sasaki, Y. Tanaka, N. Okumura, K. Nonaka, T. Takahashi, K. Yamaguchi and K. Yoshida, “Surgical Indications for Multiple and Synchronous and Liver Metastases from Colorectal Cancer,” Hepatogastroenterol, in press.
[40] U. Settmacher, Y. Dittmar, T. Knosel, U. Schone, M. Heise, K. Jandt and A. K. Altendorf-Hoffmann, “Predictors of Long-Term Survival in Patients with Colorectal Liver Metastases: A Single Center Study and Review of the Literature,” International Journal of Colorectal Disease, Vol. 26, No. 8, 2011, pp. 1195-1197. doi:10.1007/s00384-011-1195-7
[41] R. J. De Haas, R. Adam, D. A. Wicherts, D. Azoulay, H. Bismuth, E. Vibert, C. Salloum, F. Perdigao, A. Benkabbou and D. Castaing, “Comparison of Simultaneous or Delayed Liver Surgery for Limited Synchronous Colorectal Metastases,” British Journal of Surgery, Vol. 97, No. 8, 2010, pp. 1279-1289. doi:10.1002/bjs.7106

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.