Login Register Cart 0
Mini-Review Article

The Extracapsular Lymph Node Extension Predicts Outcomes in Colorectal Cancer: A Short Review

Author(s): Rachid Jabi*, Ouissam Al Jarroudi and Mohammed Bouziane

Volume 23, Issue 4, 2022

Published on: 05 October, 2021

Page: [358 - 363] Pages: 6

DOI: 10.2174/1389450122666211005114122

Price: $65

Open Access Journals Promotions 2
Abstract

Background: The extension of the metastatic lymph nodes through the capsule to the adipose tissue in the perinodal or extra-nodal defines the extra-nodal extension (ENE). ENE represents an important prognostic factor in multiple cancers, which is considered as a prognostic parameter in different tumor-node-metastasis (TNM) classifications.

Introduction: Colorectal cancer (CRC) is ranked third in order of frequency, after successively lung and breast cancer. Lymph node metastasis has been validated as a significant negative prognostic factor for survival in colorectal cancer (CRC), which is improved by the adjuvant. Despite the use of ENE as an important and validated prognostic factor in multiple cancers, ENE is not yet taken into account in the CCR staging system.

Method: The present short review aims to discuss the prognostic impact of ENE on CRC according to the emerging evidence. To conduct this study, we have reported the results of all available studies following the scientific rationale in three parts: retrospective studies, prospective studies, and meta-analyses.

Result: ENE has a negative impact on the prognosis of colorectal cancer but is not yet used in practice in colorectal cancer.

Conclusion: We, therefore, propose to carry out randomized clinical trials to study this subject better and strengthen its value in management strategies.

Keywords: Colorectal cancer, lymph node metastasis, extra-nodal extension, prognosis, ENE in CRC, chemotherapy.

« Previous Next »
Graphical Abstract

[1]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424. [Erratum in: CA Cancer J Clin. 2020 Jul;70]. [4]. [:313. PMID: 30207593].
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Bailey CE, Hu CY, You YN, et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg 2015; 150(1): 17-22. [Erratum in: JAMA Surg. 2015 Mar 1;150]. [3]. [:277. PMID: 25372703; PMCID: PMC4666003].
[http://dx.doi.org/10.1001/jamasurg.2014.1756] [PMID: 25372703]
[3]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018; 68(1): 7-30.
[http://dx.doi.org/10.3322/caac.21442] [PMID: 29313949]
[4]
Lea D, Håland S, Hagland HR, Søreide K. Accuracy of TNM staging in colorectal cancer: A review of current culprits, the modern role of morphology and stepping-stones for improvements in the molecular era. Scand J Gastroenterol 2014; 49(10): 1153-63.
[http://dx.doi.org/10.3109/00365521.2014.950692] [PMID: 25144865]
[5]
Weiser MR. AJCC 8th Edition: Colorectal cancer. Ann Surg Oncol 2018; 25(6): 1454-5.
[http://dx.doi.org/10.1245/s10434-018-6462-1] [PMID: 29616422]
[6]
Lykke J, Roikjaer O, Jess P. The relation between lymph node status and survival in Stage I-III colon cancer: results from a prospective nationwide cohort study. Colorectal Dis 2013; 15(5): 559-65.
[http://dx.doi.org/10.1111/codi.12059] [PMID: 23061638]
[7]
Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart AK. Revised TN categorization for colon cancer based on national survival outcomes data. J Clin Oncol 2010; 28(2): 264-71.
[http://dx.doi.org/10.1200/JCO.2009.24.0952] [PMID: 19949014]
[8]
Huang B, Chen C, Ni M, Mo S, Cai G, Cai S. Log odds of positive lymph nodes is a superior prognostic indicator in stage III rectal cancer patients: A retrospective analysis of 17,632 patients in the SEER database. Int J Surg 2016; 32: 24-30.
[http://dx.doi.org/10.1016/j.ijsu.2016.06.002] [PMID: 27321382]
[9]
Veronese N, Nottegar A, Pea A, et al. Prognostic impact and implications of extracapsular lymph node involvement in colorectal cancer: A systematic review with meta-analysis. Ann Oncol 2016; 27(1): 42-8.
[http://dx.doi.org/10.1093/annonc/mdv494] [PMID: 26483050]
[10]
Al Sahaf O, Myers E, Jawad M, Browne TJ, Winter DC, Redmond HP. The prognostic significance of extramural deposits and extracapsular lymph node invasion in colon cancer. Dis Colon Rectum 2011; 54(8): 982-8.
[http://dx.doi.org/10.1097/DCR.0b013e31821c4944] [PMID: 21730787]
[11]
Kim CW, Kim J, Park Y, et al. Prognostic Implications of Extranodal Extension in Relation to Colorectal Cancer Location. Cancer Res Treat 2019; 51(3): 1135-43. [Erratum in: Cancer Res Treat. 2021 Jul;53]. [3]. [:893. PMID: 30514068; PMCID: PMC6639205].
[http://dx.doi.org/10.4143/crt.2018.392] [PMID: 30514068]
[12]
Kim H, Shin S, Kim Y, et al. The clinicopathologic significance of extranodal tumor extension in locally advanced (pT3) colorectal adenocarcinoma and its association with the loss of E-cadherin expression. Int J Clin Exp Pathol 2019; 12(9): 3417-25.
[PMID: 31934185]
[13]
Lee SH, Kim H, Paik SS, Lee WM, Lee KH, Ahn BK. The usefulness of the status of extranodal tumor extension as a factor that can predict the recurrence of stage III colorectal cancer. Acta Chir Belg 2019; 119(6): 384-9.
[http://dx.doi.org/10.1080/00015458.2018.1549393] [PMID: 30614387]
[14]
Fujii T, Tabe Y, Yajima R, et al. Process of distant lymph node metastasis in colorectal carcinoma: implication of extracapsular invasion of lymph node metastasis. BMC Cancer 2011; 11: 216.
[http://dx.doi.org/10.1186/1471-2407-11-216] [PMID: 21635742]
[15]
Suzuki H, Fujii T, Asao T, et al. Extracapsular lymph node involvement is associated with colorectal liver metastases and impact outcome after hepatectomy for colorectal metastases. World J Surg 2014; 38(8): 2079-88.
[http://dx.doi.org/10.1007/s00268-014-2488-0] [PMID: 24615606]
[16]
Heide J, Krüll A, Berger J. Extracapsular spread of nodal metastasis as a prognostic factor in rectal cancer. Int J Radiat Oncol Biol Phys 2004; 58(3): 773-8.
[http://dx.doi.org/10.1016/S0360-3016(03)01616-X] [PMID: 14967433]
[17]
Kim H, Rehman A, Chung Y, et al. Clinicopathologic significance of extranodal tumor extension in colorectal adenocarcinoma with regional lymph node metastasis. Gastroenterol Res Pract 2016; 2016: 5620765.
[http://dx.doi.org/10.1155/2016/5620765] [PMID: 27195006]
[18]
Yano H, Saito Y, Kirihara Y, Takashima J. Tumor invasion of lymph node capsules in patients with Dukes C colorectal adenocarcinoma. Dis Colon Rectum 2006; 49(12): 1867-77.
[http://dx.doi.org/10.1007/s10350-006-0733-9] [PMID: 17080279]
[19]
Nizri E, Greenman-Maaravi N, Bar-David S, et al. Analysis of histological and immunological parameters of metastatic lymph nodes from colon cancer patients reveals that T-helper 1 type immune response is associated with improved overall survival. Medicine (Baltimore) 2016; 95(45): e5340.
[http://dx.doi.org/10.1097/MD.0000000000005340] [PMID: 27828856]
[20]
Kim CW, Kim J, Yeom SS, et al. Extranodal extension status is a powerful prognostic factor in stage III colorectal cancer. Oncotarget 2017; 8(37): 61393-403.
[http://dx.doi.org/10.18632/oncotarget.18223] [PMID: 28977872]
[21]
Wind J, ten Kate FJ, Kiewiet JJ, et al. The prognostic significance of extracapsular lymph node involvement in node positive patients with colonic cancer. Eur J Surg Oncol 2008; 34(4): 390-6.
[http://dx.doi.org/10.1016/j.ejso.2007.05.011] [PMID: 17614246]
[22]
Fujii T, Tabe Y, Yajima R, et al. Extracapsular invasion as a risk factor for disease recurrence in colorectal cancer. World J Gastroenterol 2011; 17(15): 2003-6.
[http://dx.doi.org/10.3748/wjg.v17.i15.2003] [PMID: 21528079]
[23]
Komuta K, Okudaira S, Haraguchi M, Furui J, Kanematsu T. Identification of extracapsular invasion of the metastatic lymph nodes as a useful prognostic sign in patients with resectable colorectal cancer. Dis Colon Rectum 2001; 44(12): 1838-44.
[http://dx.doi.org/10.1007/BF02234464] [PMID: 11742171]
[24]
Kim YI, Cho H, Kim CW, et al. Prognostic impact of extranodal extension in rectal cancer patients undergoing radical resection after preoperative chemoradiotherapy. Clin Colorectal Cancer 2021; 20(1): e35-42.
[http://dx.doi.org/10.1016/j.clcc.2020.08.004] [PMID: 33191166]
[25]
Piredda ML, Ammendola S, Sciammarella C, et al. Colorectal cancer with microsatellite instability: Right-sided location and signet ring cell histology are associated with nodal metastases, and extranodal extension influences disease-free survival. Pathol Res Pract 2021; 224: 153519.
[http://dx.doi.org/10.1016/j.prp.2021.153519] [PMID: 34119815]
[26]
Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017; 67(2): 93-9.
[http://dx.doi.org/10.3322/caac.21388] [PMID: 28094848]
[27]
Bhattacharya P, Mukherjee R. Lymph node extracapsular extension as a marker of aggressive phenotype: Classification, prognosis and associated molecular biomarkers. Eur J Surg Oncol 2021; 47(4): 721-31.
[http://dx.doi.org/10.1016/j.ejso.2020.09.005] [PMID: 32948393]
[28]
Zhang N, Deng J, Sun W, et al. Extranodal soft tissue metastasis as an independent prognostic factor in gastric cancer patients aged under 70 years after curative gastrectomy. Ann Transl Med 2020; 8(6): 376.
[http://dx.doi.org/10.21037/atm.2020.02.09] [PMID: 32355820]
[29]
Yin DT, Yu K, Lu RQ, Li X, Xu J, Lei M. Prognostic impact of minimal extrathyroidal extension in papillary thyroid carcinoma. Medicine (Baltimore) 2016; 95(52): e5794.
[http://dx.doi.org/10.1097/MD.0000000000005794] [PMID: 28033304]
[30]
Mois E, Graur F, Hajjar NA, et al. The influence of circumferential resection margins on survival following rectal cancer surgery. Ann Ital Chir 2017; 88: S0003469X16026300.
[31]
Hu G, Li L, Hu K. Clinical implications of perineural invasion in patients with colorectal cancer. Medicine (Baltimore) 2020; 99(17): e19860.
[http://dx.doi.org/10.1097/MD.0000000000019860] [PMID: 32332645]
[32]
Nagtegaal ID, Knijn N, Hugen N, et al. Tumor deposits in colorectal cancer: Improving the value of modern staging-a systematic review and meta-analysis. J Clin Oncol 2017; 35(10): 1119-27.
[http://dx.doi.org/10.1200/JCO.2016.68.9091] [PMID: 28029327]
[33]
Brabender J, Bollschweiler E, Hölscher AH, et al. The prognostic impact of extracapsular lymph node involvement in rectal cancer patients: Implications for staging and adjuvant treatment strategies. Oncol Lett 2012; 3(4): 825-30.
[http://dx.doi.org/10.3892/ol.2012.569] [PMID: 22741001]
[34]
Lupattelli M, Maranzano E, Bellavita R, et al. Adjuvant radiochemotherapy in high-risk rectal cancer results of a prospective non-randomized study. Tumori 2001; 87(4): 239-47.
[http://dx.doi.org/10.1177/030089160108700406] [PMID: 11693802]
[35]
Leijssen LGJ, Dinaux AM, Amri R, et al. Impact of intramural and extramural vascular invasion on stage II-III colon cancer outcomes. J Surg Oncol 2019; 119(6): 749-57.
[http://dx.doi.org/10.1002/jso.25367] [PMID: 30644557]
[36]
Druzhkova I, Ignatova N, Prodanets N, et al. E-Cadherin in Colorectal Cancer: Relation to Chemosensitivity. Clin Colorectal Cancer 2019; 18(1): e74-86.
[http://dx.doi.org/10.1016/j.clcc.2018.10.003] [PMID: 30415989]
[37]
Gao M, Zhang X, Li D, He P, Tian W, Zeng B. Expression analysis and clinical significance of eIF4E, VEGF-C, E-cadherin and MMP-2 in colorectal adenocarcinoma. Oncotarget 2016; 7(51): 85502-14.
[http://dx.doi.org/10.18632/oncotarget.13453] [PMID: 27907907]
[38]
Hu Y, Dai M, Zheng Y, et al. Epigenetic suppression of E-cadherin expression by Snail2 during the metastasis of colorectal cancer. Clin Epigenetics 2018; 10(1): 154.
[http://dx.doi.org/10.1186/s13148-018-0592-y] [PMID: 30541610]
[39]
Tsai MS, Su YH, Ho MC, et al. Clinicopathological features and prognosis in resectable synchronous and metachronous colorectal liver metastasis. Ann Surg Oncol 2007; 14(2): 786-94.
[http://dx.doi.org/10.1245/s10434-006-9215-5] [PMID: 17103254]
[40]
Ganesh K, Stadler ZK, Cercek A, et al. Immunotherapy in colorectal cancer: rationale, challenges and potential. Nat Rev Gastroenterol Hepatol 2019; 16(6): 361-75.
[http://dx.doi.org/10.1038/s41575-019-0126-x] [PMID: 30886395]
[41]
Tolba MF. Revolutionizing the landscape of colorectal cancer treatment: The potential role of immune checkpoint inhibitors. Int J Cancer 2020; 147(11): 2996-3006.
[http://dx.doi.org/10.1002/ijc.33056] [PMID: 32415713]
[42]
Kim HJ, Choi GS. Clinical implications of lymph node metastasis in colorectal cancer: Current status and future perspectives. Ann Coloproctol 2019; 35(3): 109-17.
[http://dx.doi.org/10.3393/ac.2019.06.12] [PMID: 31288500]
[43]
Qiu HB, Chen G, Keshari RP, et al. The extramural metastasis might be categorized in lymph node staging for colorectal cancer. BMC Cancer 2011; 11(1): 414.
[http://dx.doi.org/10.1186/1471-2407-11-414] [PMID: 21943144]
[44]
Lino-Silva LS, Sánchez-Acosta CI, Salcedo-Hernández RA, Zepeda-Najar C. Extracapsular extension does not decrease overall survival in rectal cancer patients with lymph node metastasis following neoadjuvant chemoradiotherapy. Gastroenterol Insights 2020; 11: 11-9.
[http://dx.doi.org/10.3390/gastroent11020004]
[45]
Luchini C, Wood LD, Cheng L, et al. Extranodal extension of lymph node metastasis is a marker of poor prognosis in oesophageal cancer: A systematic review with meta-analysis. J Clin Pathol 2016; 69(11): 956-61.
[http://dx.doi.org/10.1136/jclinpath-2016-203830] [PMID: 27387986]
[46]
Luchini C, Veronese N, Nottegar A, et al. Extranodal extension of nodal metastases is a poor prognostic moderator in non-small cell lung cancer: A meta-analysis. Virchows Arch 2018; 472(6): 939-47.
[http://dx.doi.org/10.1007/s00428-018-2309-1] [PMID: 29392400]
[47]
Luchini C, Fleischmann A, Boormans JL, et al. Extranodal extension of lymph node metastasis influences recurrence in prostate cancer: A systematic review and meta-analysis. Sci Rep 2017; 7(1): 2374.
[http://dx.doi.org/10.1038/s41598-017-02577-4] [PMID: 28539662]
[48]
Veronese N, Fassan M, Wood LD, et al. Extranodal Extension of Nodal Metastases Is a Poor Prognostic Indicator in Gastric Cancer: A Systematic Review and Meta-analysis. J Gastrointest Surg 2016; 20(10): 1692-8.
[http://dx.doi.org/10.1007/s11605-016-3199-7] [PMID: 27412320]

Rights & Permissions Print Cite
Article Metrics
56
1
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
World Prematurity Day
© 2024 Bentham Science Publishers | Privacy Policy