Prognostic Value of Negative Lymph Nodes Count in Solid Tumors
|LI Jinzhou1, HUANG Zeping2, MU Yanxi1, YAO Yalong1, WANG Wenjie2, LIU Haipeng2, LIU Jie1, WANG Zhou1, CHEN Xiao2
|1. The Second Clinical Medical College of Lanzhou University, Lanzhou 730000, China; 2. Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou 730000, China
Abstract The postoperative pathological staging system (pTNM) has become an important reference for the selection of various tumor treatment strategies and prognosis evaluation at a global scale, and is a powerful predictor of the prognosis of a variety of solid tumors, but the prognosis is still different in patients with the same pTNM staging. In recent years, studies have confirmed that the negative lymph nodes count (NLNC) is related to the prognosis of a variety of solid tumors. Higher NLNC can improve the prognosis of cancer patients, and NLNC can reduce staging migration, which is expected to be a supplement to the pTNM staging system. This article reviews the value of NLNC in the prognosis of solid tumors.
Negative lymph nodes count
Pathological staging system
|Fund:Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital (No. CY2019-BJ06); Innovative Research Foundation of the Higher Education Institutions of Gansu Province (No. 2020B-048); Cuiying Student Research Cultivation Program” of Lanzhou University Second Hospital (No. CYXZ2020-16); Science and Technology Program of Lanzhou (No. 2020-ZD-88, No. 2022-ZD-107)
Issue Date: 11 August 2022
|  Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020:
GLOBOCAN Estimates of Incidence and Mortality Worldwide
for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021,
 Fang C, Wang W, Deng JY, et al. Proposal and validation of a
modified staging system to improve the prognosis predictive
performance of the 8th AJCC/UICC pTNM staging system
for gastric adenocarcinoma: a multicenter study with external
validation[J]. Cancer Commun (Lond), 2018, 38(1): 67.
 Huang CM, Lin JX, Zheng CH, et al. Effect of negative lymph
node count on survival for gastric cancer after curative distal
gastrectomy[J]. Eur J Surg Oncol, 2011, 37(6): 481-487.
 Shi RL, Chen Q, Ding JB, et al. Increased number of negative
lymph nodes is associated with improved survival outcome in
node positive gastric cancer following radical gastrectomy[J].
Oncotarget, 2016, 7(23): 35084-35091.
 Huang JY, Xu YY, Li M, et al. The prognostic impact of occult
lymph node metastasis in node-negative gastric cancer: a
systematic review and meta-analysis[J]. Ann Surg Oncol, 2013,
 Yamashita H, Deng J, Liang H, et al. Re-evaluating the prognostic
validity of the negative to positive lymph node ratio in nodepositive
gastric cancer patients[J]. Surgery, 2017, 161(6):
 中华人民共和国国家卫生健康委员会. 胃癌诊疗规范(2018年
版)[J]. 中华消化病与影像杂志(电子版), 2019, 9(3): 118-144.
[National Health Commission of the People’s Republic of China.
Guidelines for the diagnosis and treatment of gastric cancer (2018
edition)[J]. Zhonghua Xiao Hua Bing Yu Ying Xiang Za Zhi (Dian
Zi Ban), 2019, 9(3): 118-144.]
 Hoshi H. Management of Gastric Adenocarcinoma for General
Surgeons[J]. Surg Clin North Am, 2020, 100(3): 523-534.
 Zhang N, Deng J, Wang W, et al. Negative lymph node count as an
independent prognostic factor in stage Ⅲ patients after curative
gastrectomy: A retrospective cohort study based on a multicenter
database[J]. Int J Surg, 2020, 74: 44-52.
 Min SH, Won Y, Lee K, et al. Laparoscopic gastrectomy and
metastasectomy for stage Ⅳ gastric cancer[J]. Surg Endosc, 2021,
 Zhuo C, Ying M, Lin R, et al. Negative lymph node count is
a significant prognostic factor in patient with stage Ⅳ gastric
cancer after palliative gastrectomy[J]. Oncotarget, 2017, 8(41):
 Jiang J, Chen J, Zhang H, et al. Combination of the ratio between
metastatic and harvested lymph nodes and negative lymph node
count as a prognostic indicator in advanced gastric cancer: a
retrospective cohort study[J]. J Gastrointest Oncol, 2021, 12(5):
 In H, Solsky I, Palis B, et al. Validation of the 8th Edition of the
AJCC TNM Staging System for Gastric Cancer using the National
Cancer Database[J]. Ann Surg Oncol, 2017, 24(12): 3683-3691.
 Sugawara K, Yamashita H, Uemura Y, et al. Numeric pathologic
lymph node classification shows prognostic superiority to
topographic pN classification in esophageal squamous cell
carcinoma[J]. Surgery, 2017, 162(4): 846-856.
 Yu L, Zhang XT, Guan SH, et al. The Number of Negative Lymph
Nodes is Positively Associated with Survival in Esophageal
Squamous Cell Carcinoma Patients in China[J]. Open Med (Wars),
2020, 15: 152-159.
 Wu H, Liu C, Xu M, et al. Prognostic value of the number of
negative lymph nodes in esophageal carcinoma without lymphatic
metastasis[J]. Thorac Cancer, 2018, 9(9): 1129-1135.
 Ma M, Tang P, Jiang H, et al. Number of negative lymph nodes
as a prognostic factor in esophageal squamous cell carcinoma[J].
Asia Pac J Clin Oncol, 2017, 13(5): e278-e283.
 Brunner M, Merkel S, Krautz C, et al. The Prognostic Value of
the Number of Harvested Negative Lymph Nodes in Patients
Treated by Esophagectomy With or Without Neoadjuvant
Chemoradiation[J]. Anticancer Res, 2020, 40(5): 2833-2840.
 Zhou L, Zhao Y, Zheng Y, et al. The Prognostic Value of the
Number of Negative Lymph Nodes Combined with Positive
Lymph Nodes in Esophageal Cancer Patients: A Propensity-
Matched Analysis[J]. Ann Surg Oncol, 2020, 27(6): 2042-2050.
 Wang Y, Zhang X, Zhang X, et al. Prognostic value of the extent
of lymphadenectomy for esophageal cancer-specific survival
among T1 patients[J]. BMC Cancer, 2021, 21(1): 403.
 West NP, Hohenberger W, Weber K, et al. Complete mesocolic
excision with central vascular ligation produces an oncologically
superior specimen compared with standard surgery for carcinoma
of the colon[J]. J Clin Oncol, 2010, 28(2): 272-278.
 Quan Q, Zhu M, Liu S, et al. Positive impact of the negative lymph
node count on the survival rate of stage Ⅲ colon cancer with pN1
and right-side disease[J]. J Cancer, 2019, 10(4): 1052-1059.
 He WZ, Xie QK, Hu WM, et al. An increased number of negative
lymph nodes is associated with a higher immune response and
longer survival in colon cancer patients[J]. Cancer Manag Res,
2018, 10: 1597-1604.
 Sun Y, Zhang Y, Huang Z, et al. Prognostic Implication of
Negative Lymph Node Count in ypN+ Rectal Cancer after
Neoadjuvant Chemoradiotherapy and Construction of a Prediction
Nomogram[J]. J Gastrointest Surg, 2019, 23(5): 1006-1014.
 Li X, Lu H, Xu K, et al. Negative lymph node count is an
independent prognostic factor for patients with rectal cancer who
received preoperative radiotherapy[J]. BMC Cancer, 2017, 17(1): 227.
 Cui J, Zhang L, Yang L, et al. The prognostic significance of the
treatment response of regional lymph nodes and the refinement of
the current TNM staging system in locally advanced rectal cancer
after neoadjuvant chemoradiotherapy[J]. Cancer Med, 2020, 9(24): 9373-9384.
 Ogino S, Nosho K, Irahara N, et al. Negative lymph node count is
associated with survival of colorectal cancer patients, independent
of tumoral molecular alterations and lymphocytic reaction[J]. Am
J Gastroenterol, 2010, 105(2): 420-433.
 Hickman L, Contreras C. Gallbladder Cancer: Diagnosis, Surgical
Management, and Adjuvant Therapies[J]. Surg Clin North Am,
2019, 99(2): 337-355.
 Krell RW, Wei AC. Gallbladder cancer: surgical management[J].
Chin Clin Oncol, 2019, 8(4): 36.
 Lin JY, Bai DS, Zhou BH, et al. Positive relationship between
number of negative lymph nodes and duration of gallbladder
cancer cause-specific survival after surgery[J]. Cancer Manag Res,
2018, 10: 6961-6969.
 Hong EK, Kim KK, Lee JN, et al. Surgical outcome and prognostic
factors in patients with gallbladder carcinoma[J]. Korean J
Hepatobiliary Pancreat Surg, 2014, 18(4): 129-137.
 Conci S, Ruzzenente A, Sandri M, et al. What is the most accurate
lymph node staging method for perihilar cholangiocarcinoma?
Comparison of UICC/AJCC pN stage, number of metastatic
lymph nodes, lymph node ratio, and log odds of metastatic lymph
nodes[J]. Eur J Surg Oncol, 2017, 43(4): 743-750.
 Gao Y, Xu D, Wu YS, et al. Increasing negative lymph node
count is independently associated with improved long-term
survival in resectable perihilar cholangiocarcinomas[J]. Medicine
(Baltimore), 2019, 98(15): e14943.
 Wang X, Yin Z, Wang D, et al. Greater negative lymph node count
predicts favorable survival of patients with breast cancer in the
setting of neoadjuvant chemotherapy and mastectomy[J]. Future
Oncol, 2019, 15(32): 3701-3709.
 Yang J, Long Q, Li H, et al. The value of positive lymph nodes
ratio combined with negative lymph node count in prediction of
breast cancer survival[J]. J Thorac Dis, 2017, 9(6): 1531-1537.
 Wang QX, Cai YF, Chen YY, et al. Additional Prognostic Value
of Lymph Node Ratio (LNR) and Number of Negative Lymph
Nodes (NLNs) in Chinese Patients with Triple Negative Breast
Cancer[J]. Ann Clin Lab Sci, 2017, 47(1): 68-75.
 Zhao X, Wei J, Li X, et al. Increasing negative lymph node count
predicts favorable OS and DSS in breast cancer with different
lymph node-positive subgroups[J]. PLoS One, 2018, 13(3):
 Abd-Elhay FA, Elhusseiny KM, Kamel MG, et al. Negative
Lymph Node Count and Lymph Node Ratio Are Associated With
Survival in Male Breast Cancer[J]. Clin Breast Cancer, 2018,
 Wang H, Zhang C, Kong L, et al. Better survival in PMRT of female
breast cancer patients with>5 negative lymph nodes: A populationbased
study[J]. Medicine (Baltimore), 2017, 96(4): e5998.
 Zhou X, Wu C, Cheng Q. Negative Lymph Node Count Predicts
Survival of Resected Non-small Cell Lung Cancer[J]. Lung, 2020,
 Liu H, Yan T, Zhang T, et al. Proposal of a new nodal classification
for operable non-small cell lung cancer based on the number of
negative lymph nodes and the anatomical location of metastatic
lymph nodes[J]. Medicine (Baltimore), 2019, 98(20): e15645.
 Wang S, Zhang B, Li C, et al. Prognostic value of number of
negative lymph node in patients with stage II and IIIa non-small
cell lung cancer[J]. Oncotarget, 2017, 8(45): 79387-79396.
 Lu H, Guo R, Yang H, et al. The prognostic value of negative
lymph node count for patients with cervical cancer after radical
surgery[J]. Oncotarget, 2017, 9(2): 2810-2818.
 Bao X, Chen F, Qiu Y, et al. Log Odds of Positive Lymph Nodes
is Not Superior to the Number of Positive Lymph Nodes in
Predicting Overall Survival in Patients With Oral Squamous Cell
Carcinomas[J]. J Oral Maxillofac Surg, 2020, 78(2): 305-312.
 Morgagni P, Saragoni L, Scarpi E, et al. Lymph node
micrometastases in early gastric cancer and their impact on
prognosis[J]. World J Surg, 2003, 27(5): 558-561.
 Kim JJ, Song KY, Hur H, et al. Lymph node micrometastasis in
node negative early gastric cancer[J]. Eur J Surg Oncol, 2009,
 Mogoant? S?, Calot? F, Vasile I, et al. Histological and
immunohistochemical study on sentinel lymph node in colorectal
cancer-values and limitations[J]. Rom J Morphol Embryol, 2016,
 Gu P, Deng J, Wang W, et al. Impact of the number of examined
lymph nodes on stage migration in node-negative gastric cancer
patients: a Chinese multi-institutional analysis with propensity
score matching[J]. Ann Transl Med, 2020, 8(15): 938.
 Zhuo C, Xu Y, Ying M, et al. FOXP3+ Tregs: heterogeneous
phenotypes and conflicting impacts on survival outcomes in
patients with colorectal cancer[J]. Immunol Res, 2015, 61(3):
 Battaglia A, Buzzonetti A, Baranello C, et al. Metastatic tumour
cells favour the generation of a tolerogenic milieu in tumour
draining lymph node in patients with early cervical cancer[J].
Cancer Immunol Immunother, 2009, 58(9): 1363-1373.
 Cai Z, Ma J, Li S, et al. Impact of microsatellite status on negative
lymph node count and prognostic relevance after curative
gastrectomy[J]. J Surg Oncol, 2021, 123 Suppl 1: S15-S24.
 Nakakubo Y, Miyamoto M, Cho Y, et al. Clinical significance of
immune cell infiltration within gallbladder cancer[J]. Br J Cancer,
2003, 89(9): 1736-1742.
 George S, Primrose J, Talbot R, et al. Will Rogers revisited:
prospective observational study of survival of 3592 patients with
colorectal cancer according to number of nodes examined by
pathologists[J]. Br J Cancer, 2006, 95(7): 841-847.
 Canday-Alvarez A, Gil-Campos M, De la Torre-Aguilar MJ, et al.
Early Modification in Drainage of Interleukin-1β and Tumor
Necrosis Factor-α Best Predicts Surgical-Site Infection After
Cervical Neck Dissection for Oral Cancer[J]. J Oral Maxillofac
Surg, 2015, 73(6): 1189-1198.