Skip to main content
Top
Published in: BMC Gastroenterology 1/2012

Open Access 01-12-2012 | Research article

Metachronous metastasis- and survival-analysis show prognostic importance of lymphadenectomy for colon carcinomas

Authors: Tilman Laubert, Jens K Habermann, Claudia Hemmelmann, Markus Kleemann, Elisabeth Oevermann, Ralf Bouchard, Philipp Hildebrand, Thomas Jungbluth, Conny Bürk, Hamed Esnaashari, Erik Schlöricke, Martin Hoffmann, Andreas Ziegler, Hans-Peter Bruch, Uwe J Roblick

Published in: BMC Gastroenterology | Issue 1/2012

Login to get access

Abstract

Background

Lymphadenectomy is performed to assess patient prognosis and to prevent metastasizing. Recently, it was questioned whether lymph node metastases were capable of metastasizing and therefore, if lymphadenectomy was still adequate. We evaluated whether the nodal status impacts on the occurrence of distant metastases by analyzing a highly selected cohort of colon cancer patients.

Methods

1,395 patients underwent surgery exclusively for colon cancer at the University of Lübeck between 01/1993 and 12/2008. The following exclusion criteria were applied: synchronous metastasis, R1-resection, prior/synchronous second carcinoma, age < 50 years, positive family history, inflammatory bowel disease, FAP, HNPCC, and follow-up < 5 years. The remaining 421 patients were divided into groups with (TM+, n = 75) or without (TM-, n = 346) the occurrence of metastasis throughout a 5-year follow-up.

Results

Five-year survival rates for TM + and TM- were 21% and 73%, respectively (p < 0.0001). Survival rates differed significantly for N0 vs. N2, grading 2 vs. 3, UICC-I vs. -II and UICC-I vs. -III (p < 0.05). Regression analysis revealed higher age upon diagnosis, increasing N- and increasing T-category to significantly impact on recurrence free survival while increasing N-and T-category were significant parameters for the risk to develop metastases within 5-years after surgery (HR 1.97 and 1.78; p < 0.0001).

Conclusions

Besides a higher T-category, a positive N-stage independently implies a higher probability to develop distant metastases and correlates with poor survival. Our data thus show a prognostic relevance of lymphadenectomy which should therefore be retained until conclusive studies suggest the unimportance of lmyphadenectomy.
Appendix
Available only for authorised users
Literature
1.
go back to reference Johnson PM, Porter GA, Ricciardi R, Baxter NN: Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer. J Clin Oncol. 2006, 24 (22): 3570-3575. 10.1200/JCO.2006.06.8866.CrossRefPubMed Johnson PM, Porter GA, Ricciardi R, Baxter NN: Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer. J Clin Oncol. 2006, 24 (22): 3570-3575. 10.1200/JCO.2006.06.8866.CrossRefPubMed
2.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 2008, 58 (2): 71-96. 10.3322/CA.2007.0010.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 2008, 58 (2): 71-96. 10.3322/CA.2007.0010.CrossRefPubMed
3.
go back to reference Holzel D, Eckel R, Engel J: Colorectal cancer metastasis. Frequency, prognosis, and consequences. Chirurg. 2009, 80 (4): 331-340. 10.1007/s00104-008-1603-x.CrossRefPubMed Holzel D, Eckel R, Engel J: Colorectal cancer metastasis. Frequency, prognosis, and consequences. Chirurg. 2009, 80 (4): 331-340. 10.1007/s00104-008-1603-x.CrossRefPubMed
4.
go back to reference Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW: Colorectal cancer. Lancet. 2005, 365 (9454): 153-165. 10.1016/S0140-6736(05)17706-X.CrossRefPubMed Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW: Colorectal cancer. Lancet. 2005, 365 (9454): 153-165. 10.1016/S0140-6736(05)17706-X.CrossRefPubMed
5.
go back to reference Bruch HP, Schwandner O, Schiedeck TH, Roblick UJ: Actual standards and controversies on operative technique and lymph-node dissection in colorectal cancer. Langenbecks Arch Surg. 1999, 384 (2): 167-175. 10.1007/s004230050187.CrossRefPubMed Bruch HP, Schwandner O, Schiedeck TH, Roblick UJ: Actual standards and controversies on operative technique and lymph-node dissection in colorectal cancer. Langenbecks Arch Surg. 1999, 384 (2): 167-175. 10.1007/s004230050187.CrossRefPubMed
6.
go back to reference Sarli L, Bader G, Iusco D, Salvemini C, Mauro DD, Mazzeo A, Regina G, Roncoroni L: Number of lymph nodes examined and prognosis of TNM stage II colorectal cancer. Eur J Cancer. 2005, 41 (2): 272-279. 10.1016/j.ejca.2004.10.010.CrossRefPubMed Sarli L, Bader G, Iusco D, Salvemini C, Mauro DD, Mazzeo A, Regina G, Roncoroni L: Number of lymph nodes examined and prognosis of TNM stage II colorectal cancer. Eur J Cancer. 2005, 41 (2): 272-279. 10.1016/j.ejca.2004.10.010.CrossRefPubMed
7.
go back to reference Chang GJ, Rodriguez-Bigas MA, Skibber JM, Moyer VA: Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst. 2007, 99 (6): 433-441. 10.1093/jnci/djk092.CrossRefPubMed Chang GJ, Rodriguez-Bigas MA, Skibber JM, Moyer VA: Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst. 2007, 99 (6): 433-441. 10.1093/jnci/djk092.CrossRefPubMed
8.
go back to reference Wong SL, Ji H, Hollenbeck BK, Morris AM, Baser O, Birkmeyer JD: Hospital lymph node examination rates and survival after resection for colon cancer. JAMA. 2007, 298 (18): 2149-2154. 10.1001/jama.298.18.2149.CrossRefPubMed Wong SL, Ji H, Hollenbeck BK, Morris AM, Baser O, Birkmeyer JD: Hospital lymph node examination rates and survival after resection for colon cancer. JAMA. 2007, 298 (18): 2149-2154. 10.1001/jama.298.18.2149.CrossRefPubMed
9.
go back to reference Cady B: Regional lymph node metastases; a singular manifestation of the process of clinical metastases in cancer: contemporary animal research and clinical reports suggest unifying concepts. Ann Surg Oncol. 2007, 14 (6): 1790-1800. 10.1245/s10434-006-9234-2.CrossRefPubMed Cady B: Regional lymph node metastases; a singular manifestation of the process of clinical metastases in cancer: contemporary animal research and clinical reports suggest unifying concepts. Ann Surg Oncol. 2007, 14 (6): 1790-1800. 10.1245/s10434-006-9234-2.CrossRefPubMed
10.
go back to reference Oltedal S, Gilje B, Korner H, Aasprong OG, Tjensvoll K, Heikkila R, Smaaland R, Nordgard O: Detection of occult metastases in sentinel lymph nodes from colon cancer patients by K-ras mutation peptide nucleic acid clamp PCR. Ann Surg. 2010, 251 (6): 1087-1091. 10.1097/SLA.0b013e3181dae1bc.CrossRefPubMed Oltedal S, Gilje B, Korner H, Aasprong OG, Tjensvoll K, Heikkila R, Smaaland R, Nordgard O: Detection of occult metastases in sentinel lymph nodes from colon cancer patients by K-ras mutation peptide nucleic acid clamp PCR. Ann Surg. 2010, 251 (6): 1087-1091. 10.1097/SLA.0b013e3181dae1bc.CrossRefPubMed
11.
go back to reference Habermann JK, Upender MB, Roblick UJ, Kruger S, Freitag S, Blegen H, Bruch HP, Schimmelpenning H, Auer G, Ried T: Pronounced chromosomal instability and multiple gene amplifications characterize ulcerative colitis-associated colorectal carcinomas. Cancer Genet Cytogenet. 2003, 147 (1): 9-17. 10.1016/S0165-4608(03)00219-X.CrossRefPubMed Habermann JK, Upender MB, Roblick UJ, Kruger S, Freitag S, Blegen H, Bruch HP, Schimmelpenning H, Auer G, Ried T: Pronounced chromosomal instability and multiple gene amplifications characterize ulcerative colitis-associated colorectal carcinomas. Cancer Genet Cytogenet. 2003, 147 (1): 9-17. 10.1016/S0165-4608(03)00219-X.CrossRefPubMed
12.
go back to reference Birgisson H, Ghanipour A, Smedh K, Pahlman L, Glimelius B: The correlation between a family history of colorectal cancer and survival of patients with colorectal cancer. Fam Cancer. 2009, 8 (4): 555-561. 10.1007/s10689-009-9286-0.CrossRefPubMed Birgisson H, Ghanipour A, Smedh K, Pahlman L, Glimelius B: The correlation between a family history of colorectal cancer and survival of patients with colorectal cancer. Fam Cancer. 2009, 8 (4): 555-561. 10.1007/s10689-009-9286-0.CrossRefPubMed
13.
go back to reference Chan JA, Meyerhardt JA, Niedzwiecki D, Hollis D, Saltz LB, Mayer RJ, Thomas J, Schaefer P, Whittom R, Hantel A, et al: Association of family history with cancer recurrence and survival among patients with stage III colon cancer. JAMA. 2008, 299 (21): 2515-2523. 10.1001/jama.299.21.2515.CrossRefPubMedPubMedCentral Chan JA, Meyerhardt JA, Niedzwiecki D, Hollis D, Saltz LB, Mayer RJ, Thomas J, Schaefer P, Whittom R, Hantel A, et al: Association of family history with cancer recurrence and survival among patients with stage III colon cancer. JAMA. 2008, 299 (21): 2515-2523. 10.1001/jama.299.21.2515.CrossRefPubMedPubMedCentral
14.
go back to reference Wittekind C, Compton CC, Greene FL, Sobin LH: TNM residual tumor classification revisited. Cancer. 2002, 94 (9): 2511-2516. 10.1002/cncr.10492.CrossRefPubMed Wittekind C, Compton CC, Greene FL, Sobin LH: TNM residual tumor classification revisited. Cancer. 2002, 94 (9): 2511-2516. 10.1002/cncr.10492.CrossRefPubMed
15.
go back to reference Fleming I, Cooper J, Henson DE, et al: AJCC Cancer Staging Manual. 1997, Philadelphia, New York: Lippincot-Raven, 5 Fleming I, Cooper J, Henson DE, et al: AJCC Cancer Staging Manual. 1997, Philadelphia, New York: Lippincot-Raven, 5
16.
go back to reference Heinzerling JH, Anthony T, Livingston EH, Huerta S: Predictors of distant metastasis and mortality in patients with stage II colorectal cancer. Am Surg. 2007, 73 (3): 230-238.PubMed Heinzerling JH, Anthony T, Livingston EH, Huerta S: Predictors of distant metastasis and mortality in patients with stage II colorectal cancer. Am Surg. 2007, 73 (3): 230-238.PubMed
17.
go back to reference Ikeguchi M, Sakatani T, Endo K, Makino M, Kaibara N: Computerized nuclear morphometry is a useful technique for evaluating the high metastatic potential of colorectal adenocarcinoma. Cancer. 1999, 86 (10): 1944-1951. 10.1002/(SICI)1097-0142(19991115)86:10<1944::AID-CNCR10>3.0.CO;2-2.CrossRefPubMed Ikeguchi M, Sakatani T, Endo K, Makino M, Kaibara N: Computerized nuclear morphometry is a useful technique for evaluating the high metastatic potential of colorectal adenocarcinoma. Cancer. 1999, 86 (10): 1944-1951. 10.1002/(SICI)1097-0142(19991115)86:10<1944::AID-CNCR10>3.0.CO;2-2.CrossRefPubMed
19.
go back to reference Schmiegel W, Reinacher-Schick A, Arnold D, Graeven U, Heinemann V, Porschen R, Riemann J, Rodel C, Sauer R, Wieser M, et al: Update S3-guideline "colorectal cancer" 2008. Z Gastroenterol. 2008, 46 (8): 799-840. 10.1055/s-2008-1027726.CrossRefPubMed Schmiegel W, Reinacher-Schick A, Arnold D, Graeven U, Heinemann V, Porschen R, Riemann J, Rodel C, Sauer R, Wieser M, et al: Update S3-guideline "colorectal cancer" 2008. Z Gastroenterol. 2008, 46 (8): 799-840. 10.1055/s-2008-1027726.CrossRefPubMed
20.
go back to reference Chou JF, Row D, Gonen M, Liu YH, Schrag D, Weiser MR: Clinical and pathologic factors that predict lymph node yield from surgical specimens in colorectal cancer: a population-based study. Cancer. 2010, 116 (11): 2560-2570. 10.1002/cncr.25032.CrossRefPubMedPubMedCentral Chou JF, Row D, Gonen M, Liu YH, Schrag D, Weiser MR: Clinical and pathologic factors that predict lymph node yield from surgical specimens in colorectal cancer: a population-based study. Cancer. 2010, 116 (11): 2560-2570. 10.1002/cncr.25032.CrossRefPubMedPubMedCentral
21.
go back to reference West NP, Hohenberger W, Weber K, Perrakis A, Finan PJ, Quirke P: Complete mesocolic excision with central vascular ligation produces an oncologically superior specimen compared with standard surgery for carcinoma of the colon. J Clin Oncol. 2010, 28 (2): 272-278. 10.1200/JCO.2009.24.1448.CrossRefPubMed West NP, Hohenberger W, Weber K, Perrakis A, Finan PJ, Quirke P: Complete mesocolic excision with central vascular ligation produces an oncologically superior specimen compared with standard surgery for carcinoma of the colon. J Clin Oncol. 2010, 28 (2): 272-278. 10.1200/JCO.2009.24.1448.CrossRefPubMed
22.
go back to reference Pramateftakis MG: Optimizing colonic cancer surgery: high ligation and complete mesocolic excision during right hemicolectomy. Tech Coloproctol. 2010, 14: (Suppl 1):S49-51.PubMed Pramateftakis MG: Optimizing colonic cancer surgery: high ligation and complete mesocolic excision during right hemicolectomy. Tech Coloproctol. 2010, 14: (Suppl 1):S49-51.PubMed
23.
go back to reference van Schaik PM, Hermans E, van der Linden JC, Pruijt JR, Ernst MF, Bosscha K: Micro- metastases in stages I and II colon cancer are a predictor of the development of distant metastases and worse disease-free survival. Eur J Surg Oncol. 2009, 35 (5): 492-496. 10.1016/j.ejso.2008.07.011.CrossRefPubMed van Schaik PM, Hermans E, van der Linden JC, Pruijt JR, Ernst MF, Bosscha K: Micro- metastases in stages I and II colon cancer are a predictor of the development of distant metastases and worse disease-free survival. Eur J Surg Oncol. 2009, 35 (5): 492-496. 10.1016/j.ejso.2008.07.011.CrossRefPubMed
24.
go back to reference Oberg A, Stenling R, Tavelin B, Lindmark G: Are lymph node micrometastases of any clinical significance in Dukes Stages A and B colorectal cancer?. Dis Colon Rectum. 1998, 41 (10): 1244-1249. 10.1007/BF02258221.CrossRefPubMed Oberg A, Stenling R, Tavelin B, Lindmark G: Are lymph node micrometastases of any clinical significance in Dukes Stages A and B colorectal cancer?. Dis Colon Rectum. 1998, 41 (10): 1244-1249. 10.1007/BF02258221.CrossRefPubMed
25.
go back to reference Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T: Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat Rev Cancer. 2005, 5 (9): 744-749. 10.1038/nrc1694.CrossRefPubMed Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T: Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat Rev Cancer. 2005, 5 (9): 744-749. 10.1038/nrc1694.CrossRefPubMed
26.
go back to reference Gervasoni JE, Sbayi S, Cady B: Role of lymphadenectomy in surgical treatment of solid tumors: an update on the clinical data. Ann Surg Oncol. 2007, 14 (9): 2443-2462. 10.1245/s10434-007-9360-5.CrossRefPubMed Gervasoni JE, Sbayi S, Cady B: Role of lymphadenectomy in surgical treatment of solid tumors: an update on the clinical data. Ann Surg Oncol. 2007, 14 (9): 2443-2462. 10.1245/s10434-007-9360-5.CrossRefPubMed
27.
go back to reference Rudenstam CM, Zahrieh D, Forbes JF, Crivellari D, Holmberg SB, Rey P, Dent D, Campbell I, Bernhard J, Price KN, et al: Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group Trial 10-93. J Clin Oncol. 2006, 24 (3): 337-344.CrossRefPubMed Rudenstam CM, Zahrieh D, Forbes JF, Crivellari D, Holmberg SB, Rey P, Dent D, Campbell I, Bernhard J, Price KN, et al: Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group Trial 10-93. J Clin Oncol. 2006, 24 (3): 337-344.CrossRefPubMed
28.
go back to reference Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, et al: Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006, 355 (13): 1307-1317. 10.1056/NEJMoa060992.CrossRefPubMed Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, et al: Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006, 355 (13): 1307-1317. 10.1056/NEJMoa060992.CrossRefPubMed
29.
go back to reference Gerling M, Meyer KF, Fuchs K, Igl BW, Fritzsche B, Ziegler A, Bader F, Kujath P, Schimmelpenning H, Bruch HP, et al: High Frequency of Aneuploidy Defines Ulcerative Colitis-Associated Carcinomas: A Comparative Prognostic Study to Sporadic Colorectal Carcinomas. Ann Surg. 2010, 251 (1): 74-83.CrossRef Gerling M, Meyer KF, Fuchs K, Igl BW, Fritzsche B, Ziegler A, Bader F, Kujath P, Schimmelpenning H, Bruch HP, et al: High Frequency of Aneuploidy Defines Ulcerative Colitis-Associated Carcinomas: A Comparative Prognostic Study to Sporadic Colorectal Carcinomas. Ann Surg. 2010, 251 (1): 74-83.CrossRef
30.
go back to reference Wang J, Kulaylat M, Rockette H, Hassett J, Rajput A, Dunn KB, Dayton M: Should total number of lymph nodes be used as a quality of care measure for stage III colon cancer?. Ann Surg. 2009, 249 (4): 559-563. 10.1097/SLA.0b013e318197f2c8.CrossRefPubMed Wang J, Kulaylat M, Rockette H, Hassett J, Rajput A, Dunn KB, Dayton M: Should total number of lymph nodes be used as a quality of care measure for stage III colon cancer?. Ann Surg. 2009, 249 (4): 559-563. 10.1097/SLA.0b013e318197f2c8.CrossRefPubMed
31.
go back to reference Hashiguchi Y, Hase K, Ueno H, Mochizuki H, Kajiwara Y, Ichikura T, Yamamoto J: Prognostic significance of the number of lymph nodes examined in colon cancer surgery: clinical application beyond simple measurement. Ann Surg. 2010, 251 (5): 872-881. 10.1097/SLA.0b013e3181c0e5b1.CrossRefPubMed Hashiguchi Y, Hase K, Ueno H, Mochizuki H, Kajiwara Y, Ichikura T, Yamamoto J: Prognostic significance of the number of lymph nodes examined in colon cancer surgery: clinical application beyond simple measurement. Ann Surg. 2010, 251 (5): 872-881. 10.1097/SLA.0b013e3181c0e5b1.CrossRefPubMed
32.
go back to reference Schrag D, Cramer LD, Bach PB, Cohen AM, Warren JL, Begg CB: Influence of hospital procedure volume on outcomes following surgery for colon cancer. JAMA. 2000, 284 (23): 3028-3035. 10.1001/jama.284.23.3028.CrossRefPubMed Schrag D, Cramer LD, Bach PB, Cohen AM, Warren JL, Begg CB: Influence of hospital procedure volume on outcomes following surgery for colon cancer. JAMA. 2000, 284 (23): 3028-3035. 10.1001/jama.284.23.3028.CrossRefPubMed
Metadata
Title
Metachronous metastasis- and survival-analysis show prognostic importance of lymphadenectomy for colon carcinomas
Authors
Tilman Laubert
Jens K Habermann
Claudia Hemmelmann
Markus Kleemann
Elisabeth Oevermann
Ralf Bouchard
Philipp Hildebrand
Thomas Jungbluth
Conny Bürk
Hamed Esnaashari
Erik Schlöricke
Martin Hoffmann
Andreas Ziegler
Hans-Peter Bruch
Uwe J Roblick
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2012
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-12-24

Other articles of this Issue 1/2012

BMC Gastroenterology 1/2012 Go to the issue