Skip to main content

Advertisement

SpringerLink
Log in

A clinical model for predicting lymph node metastasis in submucosal invasive (T1) colorectal cancer

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background

No single histopathological feature of submucosal invasive colorectal cancer (T1-CRC) can reliably predict the risk for lymph node metastasis (LNM).

Aim

The purpose of the study was to develop a prediction model of LNM in T1-CRC.

Methods

Ninety-seven surgically resected T1-CRC at our institution were retrospectively evaluated. Morphology, localization, grading, mode of growth, presence of background adenoma, lymphoid infiltration, angiolymphatic invasion, budding, and depth of invasion were assessed. Mortality and morbidity related to surgery were also evaluated. Benefit-risk balance was assessed according to the presence of severe complications and to the presence of LNM.

Results

Fourteen cases had LNM (14 %). Eight patients (8 %) presented severe surgical complications and there were two deaths (2 %). Infiltrative growth pattern (OR 31.91, 95 % CI 2.37–428.36; p = 0.009) and the absence of lymphoid infiltrate (OR 28.75; 95 % CI 2.13–388.37; p = 0.011) were the only variables independently associated with LNM in the multivariate analysis. Both variables were included in the prediction model together with sessile morphology (OR 4.88; 95 % CI 0.81–29.3; p = 0.083) and poorly differentiated carcinoma (OR 11.77; 95 % CI 0.77–179.83; p = 0.076). A 0–100 score was developed (infiltrative growth pattern: no = 0, yes = 33; lymphoid infiltrate: no = 29, yes = 0; sessile morphology: no = 0, yes = 15; poorly differentiated: no = 0, yes = 23). Cutoff point to indicate additional surgery was set in 35 points (i.e., 10 % risk LNM). Discrimination of the prediction model was excellent (AUC 0.90; 95 % CI 0.81–0.99).

Conclusion

Combined evaluation of infiltrative growth pattern, lymphoid infiltration, poorly differentiated carcinoma, and sessile appearance showed good performance for discriminating T1-CRC patients with LNM. The benefit-risk balance was in favor of surgery when at least two of these criteria were present.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kashida H, Kudo SE (2006) Early colorectal cancer: concept, diagnosis, and management. Int J Clin Oncol 11:1–8

    Article  PubMed  Google Scholar 

  2. Nivatvongs S (2000) Surgical management of early colorectal cancer. World J Surg 24:1052–1055

    Article  CAS  PubMed  Google Scholar 

  3. Tominaga K, Nakanishi Y, Nimura S et al (2005) Predictive histopathologic factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma. Dis Colon Rectum 48:92–100

    Article  PubMed  Google Scholar 

  4. Kikuchi R, Takano M, Takagi K et al (1996) Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines. Dis Colon Rectum 38:1286–1295

    Article  Google Scholar 

  5. Sohn DK, Chang HJ, Park JW et al (2007) Histopathological risk factors for lymph node metastasis in submucosal invasive colorectal carcinoma of pedunculated or semipedunculated type. J Clin Pathol 60:912–915

    Article  PubMed Central  PubMed  Google Scholar 

  6. Okabe S, Shia J, Nash G et al (2004) Lymph node metastasis in T1 adenocarcinoma of the colon and rectum. J Gastrointest Surg 8:1032–1039

    Article  PubMed  Google Scholar 

  7. Kogler P, Kafka-Ritsch R, Öfner D et al (2013) Is limited surgery justified in the treatment of T1 colorectal cancer? Surg Endosc 27:817–825

    Article  PubMed  Google Scholar 

  8. Suh JH, Han KS, Kim BC et al (2012) Predictors for lymph node metastasis in T1 colorectal cancer. Endoscopy 44:590–595

    Article  CAS  PubMed  Google Scholar 

  9. Egashira Y, Yoshida T, Hirata I et al (2004) Analysis of pathological risk factors for lymph node metastasis of submucosal invasive colon cancer. Mod Pathol 17:503–511

    Article  CAS  PubMed  Google Scholar 

  10. Glasgow SC, Bleier JI, Burgart LJ et al (2012) Meta-analysis of histopathological features of primary colorectal cancers that predict lymph node metastases. J Gastrointest Surg 16:1019–1028

    Article  PubMed  Google Scholar 

  11. Bosch SL, Teerenstra S, de Wilt JH et al (2013) Predicting lymph node metastasis in pT1 colorectal cancer: a systematic review of risk factors providing rationale for therapy decisions. Endoscopy 45:827–841

    Article  PubMed  Google Scholar 

  12. Ishikawa Y, Akishima-Fukasawa Y, Ito K et al (2008) Histopathologic determinants of regional lymph node metastasis in early colorectal cancer. Cancer 112:924–933

    Article  PubMed  Google Scholar 

  13. Lee SH, Kang HJ, Ahn BK et al (2011) Clinicopathologic factors for prediction of lymph node metastasis in submucosally invasive colorectal carcinoma. J Korean Surg Soc 80:111–118

    Article  Google Scholar 

  14. Ueno H, Mochizuki H, Hashiguchi Y et al (2004) Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology 127:385–394

    Article  PubMed  Google Scholar 

  15. Haggitt RC, Glotzbach RE, Soffer EE et al (1985) Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polypectomy. Gastroenterology 89:328–336

    CAS  PubMed  Google Scholar 

  16. Haggitt RC (1988) Management of the patient with Carcinomas in an adenoma. Prog Clin Biol Res 279:89–99

    CAS  PubMed  Google Scholar 

  17. Shimomura T, Ishiguro S, Konishi H et al (2004) New indication for endoscopic treatment of colorectal carcinoma with submucosal invasion. J Gastroenterol Hepatol 19:48–55

    Article  PubMed  Google Scholar 

  18. Ueno H, Price AB, Wilkinson KH et al (2004) A new prognostic staging system for rectal cancer. Ann Surg 240:832–839

    Article  PubMed Central  PubMed  Google Scholar 

  19. Ogino S, Nosho K, Irahara N et al (2009) Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. Clin Cancer Res 15:6412–6420

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Hamilton SR, Aaltonen LA (eds) (2000) World Health Organization classification of tumours. Pathology and genetics of tumours of the digestive system. IARC Press, Lyon, p 314

    Google Scholar 

  21. Zlobec I, Lugli A (2009) Invasive front of colorectal cancer: dynamic interface of pro-/anti-tumor factors. World J Gastroenterol 15:5898–5906

    Article  PubMed Central  PubMed  Google Scholar 

  22. Kudo S (1993) Endoscopic mucosal resection of flat and depressed types of early colorectal cancer. Endoscopy 25:455–461

    Article  CAS  PubMed  Google Scholar 

  23. Dindo D, Demartine N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213

    Article  PubMed Central  PubMed  Google Scholar 

  24. Benizri EI, Bereder JM, Rahili A et al (2012) Additional colectomy after colonoscopic polypectomy for T1 colon cancer: a fine balance between oncologic benefit and operative risk. Int J Color Dis 27:1473–1478

    Article  Google Scholar 

  25. Harrell FE Jr (2001) Regression modelling strategies: with applications to linear models, logistic regression, and survival analysis. Springer, New York

    Book  Google Scholar 

  26. R Development Core Team (2012) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0. http://www.R-project.org. Accessed 17 May 2013

  27. Morikawa T, Kuchiba A, Qian ZR et al (2012) Prognostic significance and molecular associations of tumor growth pattern in colorectal cancer. Ann Surg Oncol 19:1944–1953

    Article  PubMed Central  PubMed  Google Scholar 

  28. Cianchi F, Messerini L, Comin CE et al (2007) Pathologic determinants of survival after resection of T3N0 (Stage IIA) colorectal cancer: proposal for a new prognostic model. Dis Colon Rectum 50:1332–1341

    Article  PubMed  Google Scholar 

  29. Zlobec I, Baker K, Minoo P et al (2009) Tumor border configuration added to TNM staging better stratifies stage II colorectal cancer patients into prognostic subgroups. Cancer 115:4021–4029

    Article  PubMed  Google Scholar 

  30. Lertprasetsuke N, Tsutsumi Y (1989) Gastric carcinoma with lymphoid stroma. Virchows Arch A Pathol Anat Histopathol 414:231–241

    Article  Google Scholar 

  31. Galon J, Costes A, Sanchez-Cabo F et al (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:1960–1964

    Article  CAS  PubMed  Google Scholar 

  32. Pages F, Kirilovsky A, Mlecnik B et al (2009) In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol 27:5944–5951

    Article  CAS  PubMed  Google Scholar 

  33. Mlecnik B, Tosolini M, Kirilovsky A et al (2011) Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 29:610–618

    Article  PubMed  Google Scholar 

  34. Tanaka S, Haruma K, Teixeria CR et al (1995) Endoscopic treatment of submucosal invasive colorectal carcinoma with special reference to risk factors for lymph node metastasis. J Gastroenterol 30:710–717

    Article  CAS  PubMed  Google Scholar 

  35. Volk EE, Goldblum JR, Petras RE et al (1995) Management and outcome of patients with invasive carcinoma arising in colorectal polyps. Gastroenterology 109:1801–1807

    Article  CAS  PubMed  Google Scholar 

  36. Sakuragi M, Togashi K, Konishi F et al (2003) Predictive factors for lymph node metastasis in T1 stage colorectal carcinomas. Dis Colon Rectum 46:1626–1632

    Article  PubMed  Google Scholar 

  37. Yamamoto S, Watanabe M, Hasegawa H et al (2004) The risk of lymph node metastasis in T1 colorectal carcinoma. Hepatogastroenterology 51:998–1000

    PubMed  Google Scholar 

  38. Yoshii S, Nojima M, Nosho K et al (2014) Factors associated with risk for colorectal cancer recurrence after endoscopic resection of T1 tumors. Clin Gastroenterol Hepatol 12:292–302

    Article  PubMed  Google Scholar 

  39. Morneau M, Boulanger J, Charlebois P et al (2013) Laparoscopic versus open surgery for the treatment of colorectal cancer: a literature review and recommendations from the Comité de l’évolution des pratiques en oncologie. Can J Surg 56:297–310

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Ethical issues

This study was carried out with the approval by the Hospital’s Ethics Committees. The design and development followed the WMA Helsinki Declaration of 1964 and its revisions and all applicable regulations.

Conflict of interest

The authors declare that they have no conflict of interest.

Author contributions

1.- Fernando Macias-Garcia, MD (1, 5)

Conception and design, acquisition of data, analysis and interpretation of data, and drafting the article

2.- Catuxa Celeiro-Muñoz, MD (2)

Acquisition, analysis, and interpretation of histological data

3.- Lucia Lesquereux-Martinez, MD, PhD (3)

Acquisition, analysis, and interpretation of surgical data

4.- Francisco Gude-Sampedro, MD, PhD (4)

Statistical analysis support

5.- Laura Uribarri-Gonzalez, MD (1,5)

Analysis and interpretation of data, critical revision of the article for important intellectual content

6.- Ihab Abdulkader, (2), MD, PhD

Analysis and interpretation of histological data

7.- Ana Alvarez-Castro (1,5), MD

Acquisition of data

8.- J. Enrique Dominguez-Muñoz, MD, PhD (1,5)

Study supervision, critical revision of the article for important intellectual content, final approval of the article.

Author information

Authors and Affiliations

  1. Gastroenterology Department, University Hospital of Santiago de Compostela, c/Choupana s/n, 15706, Santiago de Compostela, Spain

    Fernando Macias-Garcia, Laura Uribarri-Gonzalez, Ana Alvarez-Castro & J. Enrique Dominguez-Muñoz

  2. Pathology Department, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain

    Catuxa Celeiro-Muñoz & Ihab Abdulkader

  3. Digestive Surgery Department, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain

    Lucia Lesquereux-Martinez

  4. Epidemiology Department, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain

    Francisco Gude-Sampedro

  5. Foundation for Research in Digestive Diseases (FIENAD), Santiago de Compostela, Spain

    Fernando Macias-Garcia, Laura Uribarri-Gonzalez, Ana Alvarez-Castro & J. Enrique Dominguez-Muñoz

Authors
  1. Fernando Macias-Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Catuxa Celeiro-Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucia Lesquereux-Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francisco Gude-Sampedro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laura Uribarri-Gonzalez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ihab Abdulkader
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ana Alvarez-Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. Enrique Dominguez-Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fernando Macias-Garcia.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Macias-Garcia, F., Celeiro-Muñoz, C., Lesquereux-Martinez, L. et al. A clinical model for predicting lymph node metastasis in submucosal invasive (T1) colorectal cancer. Int J Colorectal Dis 30, 761–768 (2015). https://doi.org/10.1007/s00384-015-2164-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-015-2164-3

Keywords

Search

Navigation