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.
Similar content being viewed by others
References
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
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
National Comprehensive Cancer Network (2009) NCCN Clinical Practice Guidelines in Oncology: colon cancer. J Natl Compr Canc Netw 7(8):778–831
National Comprehensive Cancer Network (2009) NCCN Clincal Practice Guidelines in Oncology: rectal cancer. J Natl Compr Canc Netw 7(8):838–881
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
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
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
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
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
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
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
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
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
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
Japanese Society for Cancer of the Colon and Rectum (ed) (2009) Japanese classification of colorectal carcinoma. Kanehara & Co., Ltd., Tokyo
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
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
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
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
Brozek J, Oxman A, Schünemann H (2008) GRADEPro version 3.2
The Cochrane Collaboration (2011) Review Manager (RevMan), version 5.1
Lau J, Ioannidis JP, Terrin N, Schmid CH, Olkin I (2006) The case of the misleading funnel plot. BMJ 333:597–600
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Labianca R, Merelli B (2010) Screening and diagnosis for colorectal cancer: present and future. Tumori 96:889–901
Saito Y, Matsuda T, Fujii T (2010) Endoscopic submucosal dissection of non-polypoid colorectal neoplasms. Gastrointest Endosc Clin N Am 20:515–524
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
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
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
Disclosures
Drs. Shanshan Mou, Roy Soetikno, Tadakasu Shimoda, Robert Rouse, and Tonya Kaltenbach have no conflicts of interest or financial ties to disclose.
Author information
Authors and Affiliations
Corresponding author
Appendix
Appendix
See Table 3
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00464-013-2835-5