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Pathologic predictive factors for lymph node metastasis in submucosal invasive (T1) colorectal cancer: a systematic review and meta-analysis

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Abstract

Background

Colorectal adenocarcinoma with depth of invasion ≤1,000 μm from the muscularis mucosa and favorable histology is now considered for local resection. We aimed to examine the strength of evidence for this emerging practice.

Methods

We searched Medline, Scopus, and Cochrane (1950–2011), then performed a meta-analysis on the risk of lymph node metastasis in nonpedunculated (sessile and nonpolypoid) T1 colorectal cancers. We included studies with nonpedunculated lesions, actual invasion depth, and pathologic factors of interest. Synchronous, polyposis or secondary cancers, and chemoradiation studies were excluded. Our primary outcome was the risk of LNM. We analyzed using Review Manager; we estimated heterogeneity using Cochran Q χ2 test and I 2. We generated summary risk ratios using a random effects model, performed sensitivity analyses, and evaluated the quality of evidence using GRADEPro.

Results

We identified 209 articles; 5 studies (n = 1213 patients) met the inclusion criteria. The risk of LNM in nonpedunculated ≤1,000 μm is 1.9 % (95 % confidence interval 0.5–4.8 %). The risk for all T1 is 13 % (95 % confidence interval 11.5–15.4 %). Characteristics protective against LNM were ≤1,000 μm invasion, well differentiation, absence of lymphatic and vascular invasion, and absence of tumor budding. We did not detect significant study heterogeneity. The quality of evidence was poor.

Conclusions

Well-differentiated nonpedunculated T1 colorectal cancer invasive into the submucosa ≤1,000 μm, without lymphovascular involvement or tumor budding, has the lowest risk of nodal metastasis. Importantly, the risk was not zero (1.9 %), and the qualitative formal analysis of data was not strong. As such, endoscopic resection alone may be adequate in select patients with submucosal invasive colorectal cancers, but more studies are needed. Overall, the quality of evidence was poor; data were from small retrospective studies from limited geographic regions.

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References

  1. Kawamura YJ, Sakuragi M, Togashi K, Okada M, Nagai H, Konishi F (2005) Distribution of lymph node metastasis in T1 sigmoid colon carcinoma: should we ligate the inferior mesenteric artery? Scand J Gastroenterol 40:858–861

    Article  PubMed  Google Scholar 

  2. Huh JW, Kim HR, Kim YJ (2010) Lymphovascular or perineural invasion may predict lymph node metastasis in patients with T1 and T2 colorectal cancer. J Gastrointest Surg 14:1074–1080

    Article  PubMed  Google Scholar 

  3. National Comprehensive Cancer Network (2009) NCCN Clinical Practice Guidelines in Oncology: colon cancer. J Natl Compr Canc Netw 7(8):778–831

    Google Scholar 

  4. National Comprehensive Cancer Network (2009) NCCN Clincal Practice Guidelines in Oncology: rectal cancer. J Natl Compr Canc Netw 7(8):838–881

    Google Scholar 

  5. Hu H, Krasinskas A, Willis J (2011) Perspectives on current tumor-node-metastasis (TNM) staging of cancers of the colon and rectum. Semin Oncol 38:500–510

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  7. Komori K, Hirai T, Kanemitsu Y, Shimizu Y, Sano T, Ito S, Senda Y, Misawa K, Ito Y, Kato T (2010) Is “depth of submucosal invasion ≥ 1, 000 μm” an important predictive factor for lymph node metastases in early invasive colorectal cancer (PT1)? Hepatogastroenterology 57:1123–1127

    PubMed  Google Scholar 

  8. Ishikawa Y, Akishima-Fukasawa Y, Ito K, Akasaka Y, Yokoo T, Ishii T, Yamazaki K, Shimokawa R, Suzuki T, Fujiwara M, Kuroda Y, Ichinose A, Kiguchi H, Ogata K, Niino H, Ebihara Y (2008) Histopathologic determinants of regional lymph node metastasis in early colorectal cancer. Cancer 112:924–933

    Article  PubMed  Google Scholar 

  9. Son HJ, Song SY, Lee WY, Yang SS, Park SH, Yang MH, Yoon SH, Chun HK (2008) Characteristics of early colorectal carcinoma with lymph node metastatic disease. Hepatogastroenterology 55:1293–1297

    PubMed  CAS  Google Scholar 

  10. Kawaura K, Fujii S, Murata Y, Hasebe T, Ishii G, Itoh T, Sano Y, Saito N, Ochiai A (2007) The lymphatic infiltration identified by D2–40 monoclonal antibody predicts lymph node metastasis in submucosal invasive colorectal cancer. Pathobiology 74:328–335

    Article  PubMed  Google Scholar 

  11. Sohn DK, Chang HJ, Park JW, Choi DH, Han KS, Hong CW, Jung KH, Kim DY, Lim SB, Choi HS, Jeong SY (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  Google Scholar 

  12. Egashira Y, Yoshida T, Hirata I, Hamamoto N, Akutagawa H, Takeshita A, Noda N, Kurisu Y, Shibayama Y (2004) Analysis of pathological risk factors for lymph node metastasis of submucosal invasive colon cancer. Mod Pathol 17:503–511

    Article  PubMed  CAS  Google Scholar 

  13. Shimomura T, Ishiguro S, Konishi H, Wakabayashi N, Mitsufuji S, Kasugai T, Manou M, Kodama T (2004) New indication for endoscopic treatment of colorectal carcinoma with submucosal invasion. J Gastroenterol Hepatol 19:48–55

    Article  PubMed  Google Scholar 

  14. Kitajima K, Fujimori T, Fujii S, Takeda J, Ohkura Y, Kawamata H, Kumamoto T, Ishiguro S, Kato Y, Shimoda T, Iwashita A, Ajioka Y, Watanabe H, Watanabe T, Muto T, Nagasako K (2004) Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J Gastroenterol 39:534–543

    Article  PubMed  Google Scholar 

  15. Japanese Society for Cancer of the Colon and Rectum (ed) (2009) Japanese classification of colorectal carcinoma. Kanehara & Co., Ltd., Tokyo

  16. Soetikno RM, Kaltenbach T, Rouse RV, Park W, Maheshwari A, Sato T, Matsui S, Friedland S (2008) Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults. JAMA 299:1027–1035

    Article  PubMed  CAS  Google Scholar 

  17. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012

    Article  PubMed  CAS  Google Scholar 

  18. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P (n.d.) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 13 Aug 2011

  19. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schunemann HJ GRADE, Group Working (2008) GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336:924–926

    Article  PubMed  Google Scholar 

  20. Brozek J, Oxman A, Schünemann H (2008) GRADEPro version 3.2

  21. The Cochrane Collaboration (2011) Review Manager (RevMan), version 5.1

  22. Lau J, Ioannidis JP, Terrin N, Schmid CH, Olkin I (2006) The case of the misleading funnel plot. BMJ 333:597–600

    Article  PubMed  Google Scholar 

  23. Tamura S, Ohkawauchi K, Yokoyama Y, Onishi S (2003) Indications and techniques for endoscopic mucosal resection in the lesions of a colorectal tumor. Dig Endosc 15:S39–S43

    Article  Google Scholar 

  24. Tanaka S, Haruma K, Kimura T, Shimizu T, Oh-e T, Koike N, Kitadai, Yoshihara M, Sumii K, Kajiyama G, Shimamoto F (1998) Possibility of curative endoscopic resection for colorectal cancer with submucosally massive invasion. Gastrointest Endosc 47:AB105

  25. Tanaka S, Haruma K, Oh-E H, Nagata S, Hirota Y, Furudoi A, Amioka T, Kitadai Y, Yoshihara M, Shimamoto F (2000) Conditions of curability after endoscopic resection for colorectal carcinoma with submucosally massive invasion. Oncol Rep 7:783–788

    PubMed  CAS  Google Scholar 

  26. Tanaka S, Haruma K, Teixeira CR, Tatsuta S, Ohtsu N, Hiraga Y, Yoshihara M, Sumii K, Kajiyama G, Shimamoto F (1995) Endoscopic treatment of submucosal invasive colorectal carcinoma with special reference to risk factors for lymph node metastasis. J Gastroenterol 30:710–717

    Article  PubMed  CAS  Google Scholar 

  27. Tateishi Y, Nakanishi Y, Taniguchi H, Shimoda T, Umemura S (2010) Pathological prognostic factors predicting lymph node metastasis in submucosal invasive (T1) colorectal carcinoma. Mod Pathol 23:1068–1072

    Article  PubMed  Google Scholar 

  28. Tominaga K, Nakanishi Y, Nimura S, Yoshimura K, Sakai Y, Shimoda T (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 

  29. Tsuruta O, Tsuji Y, Kawano H, Miyazaki S, Watanabe M, Nakahara K, Tateishi H, Fujita M, Ban S, Sata M, Toyonaga A, Morimatsu M (2000) Indication for endoscopic resection of submucosal colorectal carcinoma: special reference to lymph node metastasis. Diagn Ther Endosc 6:101–109

    Article  PubMed  CAS  Google Scholar 

  30. Ueno H, Mochizuki H, Hashiguchi Y, Shimazaki H, Aida S, Hase K, Matsukuma S, Kanai T, Kurihara H, Ozawa K, Yoshimura K, Bekku S (2004) Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology 127:385–394

    Article  PubMed  Google Scholar 

  31. Yamamoto S, Watanabe M, Hasegawa H, Baba H, Yoshinare K, Shiraishi J, Kitajima M (2004) The risk of lymph node metastasis in T1 colorectal carcinoma. Hepatogastroenterology 51:998–1000

    PubMed  Google Scholar 

  32. Yamauchi H, Togashi K, Kawamura YJ, Horie H, Sasaki J, Tsujinaka S, Yasuda Y, Konishi F (2008) Pathological predictors for lymph node metastasis in T1 colorectal cancer. Surg Today 38:905–910

    Article  PubMed  Google Scholar 

  33. Suzuki T, Sadahiro S, Mukoyama S, Ishikawa K, Yasuda S, Tajima T, Makuuchi H, Murayama C (2003) Risk of lymph node and distant metastases in patients with early invasive colorectal cancer classified as Haggitt’s level 4 invasion: image analysis of submucosal layer invasion. Dis Colon Rectum 46:203–208

    Article  PubMed  Google Scholar 

  34. Sakuragi M, Togashi K, Konishi F, Koinuma K, Kawamura Y, Okada M, Nagai H (2003) Predictive factors for lymph node metastasis in T1 stage colorectal carcinomas. Dis Colon Rectum 46:1626–1632

    Article  PubMed  Google Scholar 

  35. Rasheed S, Bowley DM, Aziz O, Tekkis PP, Sadat AE, Guenther T, Boello ML, Mcdonald PJ, Talbot IC, Northover JMA (2008) Can depth of tumour invasion predict lymph node positivity in patients undergoing resection for early rectal cancer? A comparative study between T1 and T2 cancers. Colorectal Dis 10:231–237

    Article  PubMed  CAS  Google Scholar 

  36. Okabe S, Shia J, Nash G, Wong WD, Guillem JG, Weiser MR, Temple L, Sugihara K, Paty PB (2004) Lymph node metastasis in T1 adenocarcinoma of the colon and rectum. J Gastrointest Surg 8:1032–1040

    Article  PubMed  Google Scholar 

  37. Oh-e H, Tanaka S, Kitadai Y, Shimamoto F, Yoshihara M, Haruma K (2001) Angiogenesis at the site of deepest penetration predicts lymph node metastasis of submucosal colorectal cancer. Dis Colon Rectum 44:1129–1136

    Article  PubMed  CAS  Google Scholar 

  38. Nascimbeni R, Burgart LJ, Nivatvongs S, Larson DR (2002) Risk of lymph node metastasis in T1 carcinoma of the colon and rectum. Dis Colon Rectum 45:200–206

    Article  PubMed  Google Scholar 

  39. Masaki T, Sugiyama M, Matsuoka H, Abe N, Izumisato Y, Goto A, Sakamoto A, Atomi Y (2003) Clinical utility of grading criteria for submucosal invasion in the prognosis of T1 colorectal carcinomas. J Gastroenterol 38:37–44

    Article  PubMed  Google Scholar 

  40. Makino M, Yamane N, Taniguchi T, Honboh T, Kurayoshi K, Kaibara N (2000) p53 as an indicator of lymph node metastases in invasive early colorectal cancer. Anticancer Res 20:2055–2059

    PubMed  CAS  Google Scholar 

  41. Kikuchi R, Takano M, Takagi K, Fujimoto N, Nozaki R, Fujiyoshi T, Uchida Y (1995) Management of early invasive colorectal cancer: risk of recurrence and clinical guidelines. Dis Colon Rectum 38:1286–1295

    Article  PubMed  CAS  Google Scholar 

  42. Jung SA, Yang SK, Jung HY, Hong WS, Min YI, Yoo CS, Kim JC, Kang GH (1997) The indication of endoscopic treatment for early colorectal cancer. Gastrointest Endosc 45:AB109

    Google Scholar 

  43. Huddy SPJ, Husband EM, Cook MG, Gibbs NM, Marks CG, Heald RJ (1993) Lymph node metastases in early rectal cancer. Br J Surg 80:1457–1458

    Article  PubMed  CAS  Google Scholar 

  44. Furudoi A, Tanaka S, Haruma K, Kitadai Y, Yoshihara M, Chayama K, Shimamoto F (2002) Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma. Oncology 62:157–166

    Article  PubMed  CAS  Google Scholar 

  45. Fang WL, Chang SC, Lin JK, Wang HS, Yang SH, Jiang JK, Chen WC, Lin TC (2005) Metastatic potential in T1 and T2 colorectal cancer. Hepatogastroenterology 52:1688–1691

    PubMed  Google Scholar 

  46. Choi PW, Yu CS, Jang SJ, Jung SH, Kim HC, Kim JC (2008) Risk factors for lymph node metastasis in submucosal invasive colorectal cancer. World J Surg 32:2089–2094

    Article  PubMed  Google Scholar 

  47. Beppu K, Nagahara A, Terai T, Matsumoto K, Shibuya T, Sakamoto N, Osada T, Kawabe M, Otaka M, Ogihara T, Watanabe S (2010) Clinicopathological characteristics of colorectal cancer less than 10 mm in diameter and invading submucosa and below. J Gastroenterol Hepatol 25:S57–S61

    Article  PubMed  Google Scholar 

  48. Araki Y, Isomoto H, Shirouzu K, Miura K, Iwanaga H, Okita A, Sasatomi T, Ogata Y, Morodomi T, Kakegawa T (1993) Clinicopathological characteristics of colorectal submucosal carcinoma with lymph node metastasis. Kurume Med J 40:123–127

    Article  PubMed  CAS  Google Scholar 

  49. Labianca R, Merelli B (2010) Screening and diagnosis for colorectal cancer: present and future. Tumori 96:889–901

    PubMed  Google Scholar 

  50. Saito Y, Matsuda T, Fujii T (2010) Endoscopic submucosal dissection of non-polypoid colorectal neoplasms. Gastrointest Endosc Clin N Am 20:515–524

    Article  PubMed  Google Scholar 

  51. Kaltenbach T, Saito Y, Tada K, Matsuda T, Taniguchi H, Kushima R et al (2011) Incidence of lymph node metastasis from sessile or nonpolypoid early colon cancer: stratified criteria to decide when to operate or when to watch. Gastrointest Endosc 73:AB291–AB292

    Google Scholar 

  52. Wang H, Safar B, Wexner SD, Denoya P, Berho M (2009) The clinical significance of fat clearance lymph node harvest for invasive rectal adenocarcinoma following neoadjuvant therapy. Dis Colon Rectum 52:1767–1773

    Article  PubMed  Google Scholar 

  53. Vather R, Sammour T, Kahokehr A, Connolly AB, Hill AG (2009) Lymph node evaluation and long-term survival in Stage II and Stage III colon cancer: a national study. Ann Surg Oncol 16:585–593

    Article  PubMed  Google Scholar 

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Disclosures

Drs. Shanshan Mou, Roy Soetikno, Tadakasu Shimoda, Robert Rouse, and Tonya Kaltenbach have no conflicts of interest or financial ties to disclose.

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Correspondence to Tonya Kaltenbach.

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Mou, S., Soetikno, R., Shimoda, T. et al. Pathologic predictive factors for lymph node metastasis in submucosal invasive (T1) colorectal cancer: a systematic review and meta-analysis. Surg Endosc 27, 2692–2703 (2013). https://doi.org/10.1007/s00464-013-2835-5

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