The results from the study with limited series unfortunately
did not support the evidence from Western and
Japanese series pointing out RLN as an important prognostic
factor in patients with gastric cancer[
10-
12,
14,
16-
18]. The Japanese Gastric Cancer Association (JGCA) lymph node staging system has provided a comprehensive
guide to the treatment of gastric cancer and its metastases,
otherwise the 6th edition AJCC lymph node staging
system is recently good, safe and reasonable prognostic
issue. However both staging systems involve the situation
of stage migration in the majority of percentage of
cases. The ratio has been suggested by some investigative
groups as another staging system which has tried reducing
the stage migration[
12-
14,
19]. Numerous studies have
displayed that the number of removed lymph nodes determines the correctness of tumor staging and minimizing
the condition of stage migration[
3,
20]. Authors' reports
emphasizing the number of metastatic lymph nodes along
with the specimen as an important prognostic factor in gastric cancer has influenced some changes in AJCC classification
of gastric cancer in 1997 Edition which required
removal of at least 16 lymph nodes to allow accurate staging[
4,
21]. Although inadequate lymph node retrieval
from the specimen and inter-personality difference in the
number of lymph nodes at the particular stations causes
limited lymph node removal, the most common reason
is the insufficient dissection of the lymph nodes. Wagner[
22] showed the number of perigastric and celiac lymph
nodes had big variations, which was from 16 to 93 in the
patient underwent the same type D2 lymphadenectomy.
In this limited series the reason that the average number
of lymph nodes was less than 16 (14.9) could be related to
the surgical technique and the prior one. The great amount
of patient-based studies from the centers has showed that
lymph node dissection is unsatisfactory in bigger percentage
of patients[
6,
23]. That causes an important problem
as correct staging of patients is the main factor to be treated
by aggressive adjuvant chemotherapy. Some authors
suggested that better disease control could be achieved by
the reduction of the tumor aggressiveness (the number of
metastatic lymph nodes) by widening the number of removed
lymph nodes (patients immunity), which was the
RLN[
24,
25]. The concept of the stage migration could
be explained like the more increased the observed survival
of patients the larger the number of removed lymph
nodes. Persiani[
26] stated that RLN had the lowest error
margin when D1 limited dissection had been done. Then
the hypothesis like RLN could act as a good prognostic
factor was accepted regardless of the extent of lymph dissection.
Except few data about the applicability of RLN
in patients underwent surgery with a low number of removed
lymph nodes prevents nodal grouping due to the
AJCC principles. In the study to establish the best cut-off
value the estimation of the increasing of the hazard ratio
had been used. Because the average number of removed
lymph nodes was less than 16 it was not easy to determine
a statistical difference for the stages pN3 and the last
subgroup of the RLN (>60% which corresponded to pN3
stage) (Table
5). The survival diagrams for the RLN classified
into 6 subgroups showed that the survival curves
of the patients were not expected so that curves had some
stage migrations. However the survival curves of different
total nodal stage were similar to the curves from 4
subgroups of the RLN. According to the Youden's index
the maximum J values (j=sensitivity+specificity-1) for RLN, reclassified RLN and pN stages were 0.371, 0.294
and 0.393, respectively. The cut offs of RLN, reclassified
RLN and pN stages were 20-39%, <40% and pN1,
respectively. Under these conditions the sensitivities of
variables were 85%, 82% and 88%, respectively. ROC
curve demonstrated no statistical differences between the
RLN, reclassified RLN and pN stages as prognostic factors
on the patients' survival despite of the fact that those
had significant importance on the survival after surgery
for gastric cancer with statistically significant p values
(p<0.0001) (Table
4). That could depend on the limited
series or the unsatisfactory surgical procedure with less
than 16 lymph nodes. In the Marchet's study[
27] analyzing
the impact of RLN in 432 patients underwent surgery
with less than 15 lymph nodes RLN was superior to AJCC
lymph node stages to predict survival. In the study we did
not reveal similar outcomes.
The outcomes of multivariate analysis of several prognostic
factors in the limited series, age and 2 histological
types were described as statistically significant independent
prognostic factors, which were reported by some
centers where age and depth of tumor were the prognostic
predictive value on survival[16,22,24,28]. We could not
find severe impact of the location of tumor on patients'
survival, which was of statistically significant difference
for each part of stomach. A multivariate analysis was done for the RLN and the pN stages; the latter one had significant
difference and increased hazard ratio on the patients'
survival (HR=1.78, 95% CI=1.184-2.671).
Analyzing the survival of the pN stages was not determined
by the RLN only to prevent a possible lymph node
staging migration. The survival curve for the subgroups
of the RLN demonstrated upmigration in the subgroups
with 20-39% and 60-79% but downmigration was also
displayed in the one with 40-59%. That migration was
proposed to the reclassifying of the RLN. The reclassified
RLN made the survival plots clear and improved. Otherwise,
the downmigration was noticed if the number of
removed lymph nodes was lower than that was accepted
(14) [14]. We could explain the occurred downmigration in
the study with the same argument. Between the two migrations,
the upmigration should be preferred because upmigration
allows improvement in reliability of the N stages.
In conclusion we confirmed that the stage migration
can be induced in the UICC N staging system when the
total number of metastatic lymph nodes is used by different
investigators. Such stage migration could be adjusted
by the RLN based on survival time. But the RLN was not
demonstrated an eventful variable which was a prognostic
factor for survival when comparing with pN stages while
the surgery provided less than 16 lymph nodes removed
along with the whole specimen.
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