Lymph node ratio is an independent prognostic factor for patients after resection of pancreatic cancer
Zhan et al. World Journal of Surgical Oncology
Lymph node ratio is an independent prognostic factor for patients after resection of pancreatic cancer
Han-xiang Zhan 0
Jian-wei Xu 0
Lei Wang 0
Guang-yong Zhang 0
San-yuan Hu 0
0 Department of General Surgery, Qilu hospital, Shandong University , No. 107, Wenhua West Road, Lixia District, Jinan, Shandong Province 250012 , China
Background: The prognostic value of lymph node ratio (LNR) in pancreatic cancer remains controversial. In the current retrospective study, we assessed the value of LNR on predicting the survival of postoperative patients with pancreatic cancer. Methods: Medical records of patients who underwent pancreatic resection for pancreatic cancer in the department of general surgery, Qilu Hospital, Shandong University were reviewed retrospectively. Demographic, clinicopathological, tumor-specific data, and histopathological reports were collected. Univariate and multivariate survival analyses were performed. Results: A total of 83 patients with pancreatic cancer were collected. The mean number of examined LN was 8.2 6.1 (0 to 26). Differential degree (low) (P = 0.019, hazard ratio (HR) = 2.276, 95% confidence interval (CI): 1.171 to 4.424) and LNR >0.2 (P = 0.018, HR = 2.685, 95% CI: 1.253 to 5.756) were independent adverse prognostic factors according to the multivariate survival analysis. Conclusions: Our study indicated that LNR >0.2 was an independent adverse prognostic factor for pancreatic cancer, which may provide important information for prognostic assessment.
Pancreatic cancer; Lymph node ratio; Prognosis; Surgery
Pancreatic cancer is the fourth most frequent cause of
cancer death in the United States with an overall 5-year
survival rate of 5% . Only 20% of cases can be resected
when diagnosed. However, the 5-year survival rate is
reported to range only between 15% and 25% .
Several factors are related to the prognostic outcome
of patients with resection of pancreatic cancer, including
tumor stage, histologic differentiation, tumor size, lymph
node (LN) status, and resection margin status . Of
them, the prognostic value of LN status is always
controversial. Several studies have demonstrated that LN
metastasis is associated with poor prognosis of patients
with pancreatic cancer, whereas some other studies have
not observed the associations between LN metastasis
and survival outcomes .
To assess the prognostic value of LN involvement
better, the importance of lymph node ratio (LNR) has been
highlighted, which is determined by dividing the total
number of metastatic LNs by the total number of
examined LNs . Many studies have identified that LNR is a
valuable prognostic factor in pancreatic cancer patients
. Nevertheless, its prognostic value in node-positive
patients has not been shown in other studies .
Additionally, the cutoff values of LNR are inconsistent in
different studies. LNR 0.2, 0.15, and 0.1 have all been
reported as an independent poor predictive factor [6-9].
The current study aimed to assess the prognostic value
of LNR in postoperative patients with pancreatic cancer.
This study has been approved by the ethics committee on
scientific research of Shandong University, Qilu Hospital and
has been performed in accordance with the ethical standards
and according to the Declaration of Helsinki. Written
informed consent was obtained from all subjects.
A series of 83 patients who underwent resection for
pancreatic cancer in the department of general surgery,
Qilu Hospital, Shandong University was collected for
analysis. Surgical procedures were conducted by senior
surgeons. Medical records were reviewed retrospectively,
and demographic, clinicopathological, tumor-specific
data, and histopathological reports were collected. TNM
staging was defined according to the National
Comprehensive Cancer Network (NCCN) Clinical Practice
Guidelines in Oncology (NCCN Guidelines) Pancreatic
Adenocarcinoma Version 1, 2014 (http://www.nccn.org/
data were acquired from hospital records supplemented
with telephone contact. The end point was overall
survival. Survival time was calculated according to the date
of death or as the time between the last follow-up date
and the operation date.
Statistical analysis was conducted using SPSS v.13.0
software (SPSS Inc., Chicago, IL, USA). A value of P <
0.05 was considered as statistically significant. Graphs
were produced by GraphPad Prism 5 Software
(GraphPad, San Diego, CA, USA). The Kaplan-Meier method
and Cox regression were used for univariate and
multivariate survival analyses, respectively.
The clinicopathologic characteristics of patients
A total of 83 patients with pancreatic cancer were
collected in the current study, including 53 males and 30
females, with an average age of 61.7 10.7 (range 36 to 85)
years old. The average size of the tumor diameter was 4.6
2.23 cm (range 0.5 to 14 cm). The total number of
examined LNs was range from 0 to 26, with a mean of 8.2
6.1. The average follow-up was 26.9 months (median 15, range 1 to 87 months).
Univariate and multivariate survival analyses
The median survival was 20 months. The overall 1- and
3-year survival rates were 58.6% and 42.7%, respectively.
Univariate survival analysis indicated that sex,
differential degree, LN staging, TNM staging, LNR, and total
number of examined LNs were potential prognostic
factors (Table 1, Figure 1). Multivariate analysis
demonstrated that differential degree (low) and LNR >0.2 were
independent adverse prognostic factors (P = 0.019, hazard
ratio (HR) = 2.276, 95% confidence interval (CI): 1.171 to
4.424; P = 0.018, HR = 2.685, 95% CI: 1.253 to 5.756)
LN involvement remains one of the most important
factors for predicating survival of patients with resection of
Tumor size (cm)
Lymph node staging
of examined LNs
aThe differential degree of six cases is not recorded. bNone: if the number of
censored data is more than 50% of the total, median survivals cannot be
calculated by SPSS. LN, lymph node; SE, standard error.
Table 1 Univariate analysis of factors predictive of poor
Case Univariate analysis
number (n) Overall survival 1-year P
(median SE, survival value
months) rate (%)
Figure 1 Kaplan-Meier survival curves. Left panel, survival analysis based on LNR. Right panel, survival analysis based on the total number of
examined LN. LN, lymph node; LNR, lymph node ratio.
pancreatic cancer [5,10]. However, both LN status and
the numbers of examined LNs are imperfect as the sole
predictor. LNR not only provides information regarding
the number of positive LNs but also gives an estimate of
the adequacy of LNs obtained , which is a significant
modifier of the effect of LN status and the numbers of
examined LNs on survival of patients with resected cancer
. LNR has been identified as a tool to predict outcome
in cancers of the esophagus , stomach , colon ,
and ampulla of Vater . However, the association of
LNR and overall survival in pancreatic cancer has not been
well defined. We showed that LNR is negatively correlated
with the overall survival with a cutoff value of 0.2.
There is no consensus on the best cutoff value for
LNR. Pawlik and colleagues used categories of LNR
<0.2, 0.4, and >0.4 , while House et al. used 0.18 as a
cutoff value . Ashfaq et al. indicated that LNR cutoff
of 0.1 was statistically significant for survival
discrimination . Our study demonstrated that patients with
LNR >0.2 displayed poor prognosis, as reported by
previous studies [6,7].
In addition, we evaluated the prognostic role of examined
LNs, which indicated that total number of examined LNs
12 was potentially associated with improved survival.
Several studies have reported the link between longer survival
and total number of examined LNs [18,19]. Our study might
also indicate that standard lymphadenectomy is enough,
Table 2 Multivariate analysis of factors predictive of poor
Differential degree (low)
Lymph node staging (N1)
TNM staging (III/IV)
LNR, lymph node ratio.
because the mean number of LNs resected in patients with
pancreatic cancer who underwent standard
lymphadenectomy in the randomized controlled trials (RCTs) was 13 to
17 [20-22]. Extended lymphadenectomy increases the total
number of examined LNs, but there are no significant
differences in the overall survival between patients who
underwent pancreatic cancer surgery with extended
lymphadenectomy and those who underwent operation with
standard lymphadenectomy [23,24]. On the contrary, extended
lymphadenectomy may increase postoperative morbidities
and mortalities and decrease quality of life [24,25]. Although
there was a debate on the value of extended
lymphadenectomy in the past, the ideas are beginning to converge.
Unnecessary extended lymphadenectomy should be avoided,
which has been recommended by the NCCN Clinical
Practice Guidelines in Oncology (NCCN Guidelines) Pancreatic
Adenocarcinoma Version 1, 2014.
Both the LN status and the LNR are influenced by the
total LN harvested . Valsangkar and colleagues
analyzed 14,907 patients in a national database and 902
patients treated at a single large institution, which showed
that a minimum of 13 to 16 LNs must be examined to
accurately predict survival . The mean number of the
total examined LN was 8.2 6.1 in our study, which might
not do full justice to the prognostic value of LNR.
Nevertheless, a moderate number (6 to 12 LNs) of the total
examined LN could partly predict survival . What we
need to emphasize is that the retrieval of the lymph nodes
not only depends on the scope of the lymphadenectomy
but also depends on the seriousness of the pathologist.
Only surgeons and pathologists cooperated closely may
accurately evaluate the value of LNR.
The present study demonstrated that LNR >0.2 was an
independent adverse prognostic factor, which is
powerful and useful for prognostic assessment for pancreatic
The authors declare that they have no competing interests.
HXZ, JWX, and SYH proposed the study. HXZ and JWX wrote the first draft
and collected and analyzed the data. All authors contributed to the design
and interpretation of the study and to further drafts. LW, GYZ, and SYH
revised the manuscript. All authors read and approved the final manuscript.
This work was supported by China Postdoctoral Science Foundation
(2013 M531606) and Shandong Provincial Natural Science Foundation, China
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