Skip to main content

Advertisement

Log in

Intrahepatic Lymphatic Invasion Independently Predicts Poor Survival and Recurrences after Hepatectomy in Patients with Colorectal Carcinoma Liver Metastases

  • Hepatic and Pancreatic Tumors
  • Original Papers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

D2-40 monoclonal antibody immunoreactivity is specific for lymphatic endothelium and therefore provides a marker of lymphatic invasion. We hypothesized that intrahepatic lymphatic invasion reflects the nodal status of colorectal carcinoma liver metastases and may function as an adverse prognostic factor.

Methods

A retrospective analysis of 105 consecutive patients who underwent resection for colorectal carcinoma liver metastases was conducted. Intrahepatic lymphatic invasion was declared when either single tumor cells or cell clusters were clearly visible within vessels that showed immunoreactivity for D2-40 monoclonal antibody. The median follow-up time was 124 months.

Results

Of 105 patients, 13 were classified as having intrahepatic lymphatic invasion. All tumor foci of intrahepatic lymphatic invasion were detected within the portal tracts. Intrahepatic lymphatic invasion was significantly associated with hepatic lymph node involvement (P = 0.039). Survival after resection was significantly worse in patients with intrahepatic lymphatic invasion (median survival time of 13 months; cumulative five-year survival rate of 0%) than in patients without (median survival time of 40 months; cumulative five-year survival rate of 41%; P < 0.0001). Patients with intrahepatic lymphatic invasion also showed decreased disease-free survival rates (P < 0.0001). Intrahepatic lymphatic invasion thus independently affected both survival (relative risk, 7.666; 95% confidence interval, 3.732–15.748; P < 0.001) and disease-free survival (relative risk, 4.112; 95% confidence interval, 2.185–7.738; P < 0.001).

Conclusions

Intrahepatic lymphatic invasion is associated with hepatic lymph node involvement and is an adverse prognostic factor in patients with colorectal carcinoma liver metastases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
FIG. 3.
FIG. 4.
FIG. 5.

Similar content being viewed by others

References

  1. Chang AE, Schneider PD, Sugarbaker PH, Simpson C, Culnane M, Steinberg SM. A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases. Ann Surg 1987;206:685–93

    Article  PubMed  CAS  Google Scholar 

  2. Shirai Y, Wakai T, Ohtani T, Sakai Y, Tsukada K, Hatakeyama K. Colorectal carcinoma metastases to the liver. Does primary tumor location affect its lobar distribution? Cancer 1996;77:2213–6

    Article  PubMed  CAS  Google Scholar 

  3. Elias D, Saric J, Jaeck D, et al. Prospective study of microscopic lymph node involvement of the hepatic pedicle during curative hepatectomy for colorectal metastases. Br J Surg 1996;83:942–5

    Article  PubMed  CAS  Google Scholar 

  4. August DA, Sugarbaker PH, Schneider PD. Lymphatic dissemination of hepatic metastases. Implications for the follow-up and treatment of patients with colorectal cancer. Cancer 1985;55:1490–4

    Article  PubMed  CAS  Google Scholar 

  5. Dworkin MJ, Earlam S, Fordy C, Allen-Mersh TG. Importance of hepatic artery node involvement in patients with colorectal liver metastases. J Clin Pathol 1995;48:270–2

    Article  PubMed  CAS  Google Scholar 

  6. Beckurts KTE, Hölscher AH, Thorban S, Bollschweiler E, Siewert JR. Significance of lymph node involvement at the hepatic hilum in the resection of colorectal liver metastases. Br J Surg 1997;84:1081–4

    Article  PubMed  CAS  Google Scholar 

  7. Jaeck D, Nakano H, Bachellier P, et al. Significance of hepatic pedicle lymph node involvement in patients with colorectal liver metastases: a prospective study. Ann Surg Oncol 2002;9:430–8

    Article  PubMed  Google Scholar 

  8. Lefor AT, Hughes KS, Shiloni E, et al. Intra-abdominal extrahepatic disease in patients with colorectal hepatic metastases. Dis Colon Rectum 1988;31:100–3

    Article  PubMed  CAS  Google Scholar 

  9. Sanchez-Cespedes M, Esteller M, Hibi K, et al. Molecular detection of neoplastic cells in lymph nodes of metastatic colorectal cancer patients predicts recurrence. Clin Cancer Res 1999;5:2450–4

    PubMed  CAS  Google Scholar 

  10. Yamamoto J, Sugihara K, Kosuge T, et al. Pathologic support for limited hepatectomy in the treatment of liver metastases from colorectal cancer. Ann Surg 1995;221:74–8

    Article  PubMed  CAS  Google Scholar 

  11. Shirabe K, Takenaka K, Gion T, et al. Analysis of prognostic risk factors in hepatic resection for metastatic colorectal carcinoma with special reference to the surgical margin. Br J Surg 1997;84:1077–80

    Article  PubMed  CAS  Google Scholar 

  12. Nanko M, Shimada H, Yamaoka H, et al. Micrometastatic colorectal cancer lesions in the liver. Surg Today 1998;28:707–13

    Article  PubMed  CAS  Google Scholar 

  13. Okano K, Yamamoto J, Moriya Y, Akasu T, Kosuge T, Sakamoto M, Hirohashi S. Macroscopic intrabiliary growth of liver metastases from colorectal cancer. Surgery 1999;126:829–34

    PubMed  CAS  Google Scholar 

  14. Yokoyama N, Shirai Y, Ajioka Y, Nagakura S, Suda T, Hatakeyama K. Immunohistochemically detected hepatic micrometastases predict a high risk of intrahepatic recurrence after resection of colorectal carcinoma liver metastases. Cancer 2002;94:1642–7

    Article  PubMed  Google Scholar 

  15. Sasaki A, Aramaki M, Kawano K, Yasuda K, Inomata M, Kitano S. Prognostic significance of intrahepatic lymphatic invasion in patients with hepatic resection due to metastases from colorectal carcinoma. Cancer 2002;95:105–11

    Article  PubMed  Google Scholar 

  16. Shirai Y, Tsukada K, Ohtani T, Watanabe H, Hatakeyama K. Hepatic metastases from carcinoma of the gallbladder. Cancer 1995;75:2063–8

    Article  PubMed  CAS  Google Scholar 

  17. Kahn HJ, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol 2002;15:434–40

    Article  PubMed  Google Scholar 

  18. Kahn HJ, Marks A. A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors. Lab Invest 2002;82:1255–7

    PubMed  Google Scholar 

  19. Arigami T, Natsugoe S, Uenosono Y, et al. Lymphatic invasion using D2-40 monoclonal antibody and its relationship to lymph node micrometastasis in pN0 gastric cancer. Br J Cancer 2005:93:688–93

    Article  PubMed  CAS  Google Scholar 

  20. Gombos Z, Xu X, Chu CS, Zhang PJ, Acs G. Peritumoral lymphatic vessel density and vascular endothelial growth factor C expression in early-stage squamous cell carcinoma of the uterine cervix. Clin Cancer Res 2005;11:8364–71

    Article  PubMed  CAS  Google Scholar 

  21. Van den Eynden GG, Van der Auwera I, Van Laere SJ, et al. Distinguishing blood and lymph vessel invasion in breast cancer: a prospective immunohistochemical study. Br J Cancer 2006;94:1643–9

    PubMed  Google Scholar 

  22. Greene FL, Page DL, Fleming ID, et al. AJCC Cancer Staging Manual, 6th ed. New York: Springer-Verlag, 2002

    Google Scholar 

  23. Nagakura S, Shirai Y, Yamato Y, Yokoyama N, Suda T, Hatakeyama K. Simultaneous detection of colorectal carcinoma liver and lung metastases does not warrant resection. J Am Coll Surg 2001;193:153–60

    Article  PubMed  CAS  Google Scholar 

  24. Nagakura S, Shirai Y, Suda T, Hatakeyama K. Multiple repeat resections of intra- and extrahepatic recurrences in patients undergoing initial hepatectomy for colorectal carcinoma metastases. World J Surg 2002;26:141–7

    Article  PubMed  Google Scholar 

  25. Terminology Committee of the International Hepato-Pancreato-Biliary Association: Chairman, Strasberg SM. The Brisbane 2000 Terminology of Liver Anatomy and Resections. HPB 2000;2:333–9

    Google Scholar 

  26. Rouvière H. Lymphatics of the liver, the biliary passages, and the pancreas. In: Tobias MJ, ed. Anatomy of the Human Lymphatic System. Ann Arbor, Michigan: Edwards Brothers, 1938:197–205

    Google Scholar 

  27. Shirai Y, Yoshida K, Tsukada K, Ohtani T, Muto T. Identification of the lymphatic system of the gallbladder by vital staining. Br J Surg 1992;79:659–62

    Article  PubMed  CAS  Google Scholar 

  28. Taylor M, Forster J, Langer B, Taylor BR, Greig PD, Mahut C. A study of prognostic factors for hepatic resection for colorectal metastases. Am J Surg 1997;173:467–71

    Article  PubMed  CAS  Google Scholar 

  29. Sugarbaker PH. Peritoneal surface oncology: review of a personal experience with colorectal and appendiceal malignancy. Tech Coloproctol 2005;9:95–103

    Article  PubMed  CAS  Google Scholar 

  30. Saltz LB, Cox JV, Blanke C, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 2000;343:905–14

    Article  PubMed  CAS  Google Scholar 

  31. Mackay HJ, Billingsley K, Gallinger S, et al. A multicenter phase II study of “adjuvant” irinotecan following resection of colorectal hepatic metastases. Am J Clin Oncol 2005;28:547–54

    Article  PubMed  CAS  Google Scholar 

  32. Nordlinger B, Sorbey M, Debois M, et al. Feasibility and risks of pre-operative chemotherapy (CT) with Folfox 4 and surgery for respectable colorectal cancer liver metastases (LM). Interim results of the EORTC Intergroup randomized phase III study 40983. In: ASCO Annual Meeting Proceedings 2005 (abstract 3528); 253s

  33. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335–45

    Article  PubMed  CAS  Google Scholar 

  34. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337–45

    Article  PubMed  CAS  Google Scholar 

  35. Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol 1997;15:938–46

    PubMed  CAS  Google Scholar 

  36. Weber SM, Jarnagin WR, DeMatteo RP, Blumgart LH, Fong Y. Survival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol 2000;7:643–50

    Article  PubMed  CAS  Google Scholar 

  37. Choti MA, Sitzmann JV, Tiburi MF, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 2002;235:759–66

    Article  PubMed  Google Scholar 

  38. Altendorf-Hofmann A, Scheele J. A critical review of the major indicators of prognosis after resection of hepatic metastases from colorectal carcinoma. Surg Oncol Clin N Am 2003;12:165–92

    Article  PubMed  Google Scholar 

  39. Pawlik TM, Scoggins CR, Zorzi D, et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg 2005;241:715–22

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Toshifumi Wakai MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Korita, P.V., Wakai, T., Shirai, Y. et al. Intrahepatic Lymphatic Invasion Independently Predicts Poor Survival and Recurrences after Hepatectomy in Patients with Colorectal Carcinoma Liver Metastases. Ann Surg Oncol 14, 3472–3480 (2007). https://doi.org/10.1245/s10434-007-9594-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-007-9594-2

Keywords

Navigation