(Chest. 2002;121:112-117.)
© 2002
American College of Chest Physicians
Analysis of Lobar Lymph Node Metastases Around the Bronchi of Primary and Nonprimary Lobes in Lung Cancer*
Risk of Remnant Tumor at the Root of the Nonprimary Lobes
Akira Yamanaka, MD;
Takashi Hirai, MD;
Ayuko Takahashi, MD and
Fumio Konishi, MD
*
From the Departments of Chest Surgery (Drs. Yamanaka, Hirai, and Takahashi) and Pathology (Dr. Konishi), Fukui Red Cross Hospital, Fukui, Japan.
Correspondence to: Akira Yamanaka, MD, Department of Chest Surgery, Fukui Red Cross Hospital, 2–4-1 Tsukimi, Fukui 918-8501, Japan; e-mail: akiray{at}mitene.or.jp
 |
Abstract
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Study objective: The details of lobar lymph node
metastases at the root of nonprimary lobes (NPLs) in patients with lung
cancer are still unclear.
Design: A prospective study
from February 1989 to November 2000. Lobar lymph nodes in primary lobes
(PLs) and NPLs were evaluated regardless of the location of the primary
tumor.
Patients: Two hundred forty-eight patients who
underwent surgery and had no involvement of the adjacent lobe by
primary tumor were enrolled in this study.
Measurements and
results: Lobar lymph node metastases were observed in 53 patients
(21.4%), with frequencies not different among the primary sites.
Thirty-seven patients had lobar lymph node metastases limited to the
PL, and 16 patients had metastases in the NPLs. The frequencies of
lobar lymph node metastases in NPLs were not affected by histologic
type or T classification, but they were dependent on laterality and
proximal lymph node metastases. On the right side, lobar lymph node
metastases in NPLs were observed in 9.0% of all 155 patients, in
45.2% of 31 patients with lobar lymph node metastases, and in 34.3%
of 35 patients with mediastinal lymph node metastases. They were
significantly higher in the patients with interlobar/hilar lymph node
metastases (12 of 28 patients) or with mediastinal metastases (12 of 35
patients) than in those without metastases on the right (p < 0.0001,
respectively).
Conclusions: Lobar lymph node
metastases in NPLs were frequent on the right side and became more
frequent according to the prevalence of the proximal lymph node
metastases, rather than the clinicopathologic properties of the primary
tumor itself.
Key Words: collateral lymphatic spread • extended total lobar lymphadenectomy • lobar lymph node metastases • lung cancer • lymphatic congestion • nonprimary lobe
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Introduction
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In
lung cancer, the presence of lymph node metastases is one of the most
important prognostic indexes. Although surgeons aggressively dissect
the total hilar and mediastinal lymph node systems, ipsilateral local
recurrence occurs with great frequency, and the outcome of the surgical
treatment is not satisfactory. Accordingly, the majority of
studies1
2
on lymphatic metastatic patterns
have been focused mainly on mediastinal lymph nodes, and complete
resection of primary tumor combined with aggressive mediastinal lymph
node dissection has been the standard for completeness of surgical
treatment. However, there have been only few reports regarding lobar
lymph node metastases in nonprimary lobes (NPLs),3
and it
has been unclear whether the normal lymphatic flow to the mediastinum
is preserved or modifiable in patients with lymph node involvement.
This article presents the features of metastases to lobar lymph nodes
in both the primary lobe (PL) and NPLs and their correlation with the
clinicopathologic properties of lung cancer. We evaluate the risk of
remnant tumor at the root of NPLs and the significance of dissection of
the total lobar lymph nodes also in remaining NPLs.
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Materials and Methods
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Patients
From February 1989 through November 2000, 364 patients
underwent pulmonary resection for lung cancer in our hospital. Two
hundred forty-eight patients were selected according to the following
criteria: (1) non-small cell lung cancer; (2) limited location at
sites peripheral to the orifice of the lobar bronchus; (3) no
involvement of the adjacent lobe by primary tumor; (4) lobectomy
or pneumonectomy performed; (5) no synchronous double primary lung
cancer; (6) no preoperative chemotherapy or radiotherapy; (7)
evaluation for lobar lymph nodes in both PL and NPLs regardless of the
location of the primary tumor; and (8) total dissection of the lymph
nodes (all lobar-hilar and mediastinal system), regardless of the
location of the primary tumor. For the left-side cases, accessible
superior mediastinal lymph node dissection was performed as thoroughly
as possible through the left mediastinum as a conventional procedure.
The lobar lymph nodes in NPLs were dissected from the lobar bronchi,
avoiding the branches of the pulmonary artery through the incised
pleura as thoroughly as possible. During dissection of lobar lymph
nodes in NPLs, injury to vessels or major air leakage did not occur in
any case. All patients underwent a physical examination, chest
radiography, bronchoscopy, whole-body CT, brain CT or MRI, and bone
scanning.
Lymph Node Evaluation
Lymph nodes were classified into two groups according to their
location ie, lobar-hilar lymph nodes (nodes 10 through 12)
and mediastinal lymph nodes (nodes 1 to 9). Lobar-hilar lymph nodes
consisted of hilar nodes (node 10), interlobar nodes (node 11), and
lobar nodes (node 12). Lobar lymph nodes were mapped according to their
location into node 12 upper, node 12 middle, and node 12 lower. All
patients were staged according to the new International Staging System
for Lung Cancer.4
Lymph node metastases were marked using
the mapping of the American Thoracic Society.5
Frozen
section diagnosis was not generally performed during surgery.
Statistics
All statistical analyses were performed using a software package
(StatView, version 4.5; Abacus Concepts; Berkeley, CA). The frequencies
of the various categorical outcomes in the two groups were evaluated by
two-by-two contingency 
2 with Yates’
correction for continuity, or Fisher’s Exact Test when the sample size
was small.
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Results
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Clinical Characteristics of Patients
The age of the patients ranged from 30 to 84 years
(mean ± SD, 65.0 ± 9.6 years). There were 158 men
and 90 women, a ratio of 1.76:1. There were 85 patients
with stage IA, 51 patients with stage IB, 11 patients with stage IIA,
25 patients with stage IIB, 47 patients with stage IIIA, 23 patients
with stage IIIB, and 6 patients with stage IV disease.
Bilobectomy and pneumonectomy were performed in 18 patients and
10 patients, respectively. The reasons for these surgical procedures
included: incomplete minor fissures; invasion close to the bronchus
intermedius; obvious lobar lymphadenopathy in NPLs, as judged from the
intraoperative findings; distal arterial involvement; anatomic anomaly;
and intrapulmonary metastases in the NPL.
Histologic Type, Tumor Classification, and Node
Classification According to the Primary Site
Adenocarcinoma was the predominant histologic finding in each
primary site, and there was no significant difference in histologic
types (adenocarcinoma vs nonadenocarcinoma) among the primary
sites. There were no significant differences in tumor classification
(T1 vs T2 to T4) among the primary sites. There were no significant
differences in node classification (N0 vs N1 to N3) among the primary
sites except for the left lower lobe (Table 1
).
Metastases to the Lobar, Interlobar, Hilar, and Mediastinal Lymph
Nodes According to the Primary Site
Lobar lymph node metastases were observed in 53 patients (21.4%).
The frequency of lobar lymph node metastases was not different from
those of interlobar and mediastinal lymph node metastases, but was
significantly higher than that of hilar lymph node metastases
(p = 0.0081). There were no significant differences in the
frequencies of lobar lymph node metastases among the primary sites,
between right and left cases, or between upper lobe tumor and
middle/lower lobe tumor. Of 53 patients with lobar lymph node
metastases, 37 patients (69.8%) had lobar lymph node metastases
limited to the PL (limited lobar lymph node metastasis) and 16 patients
(30.2%) had lobar lymph node metastases in NPLs (extended lobar
lymph node metastases). The frequency of lobar lymph node metastasis in
the PL (48 of 248 patients) was significantly higher than that in NPLs
(16 of 248 patients; p < 0.0001). Twenty-one of the total
metastasized 69 lobar lymph nodes (30.4%) were in NPLs. In the
per-lobe analysis, the lobar lymph node metastases in PL (48 of 248
lobar lymph nodes) were significantly more frequent than those in NPLs
(21 of 403 lobar lymph nodes; p < 0.0001). Of 53 patients with lobar
lymph node metastases, the ratio of extended lobar lymph node
metastases was significantly higher on the right side (14 of 31
patients) than on the left (2 of 22 patients; p = 0.0061), especially
for the right middle/lower lobe tumors compared with other lobe tumors
(p = 0.0034). On the right side, just less than one tenth of all the
patients and just less than one half of those with lobar lymph node
metastases had extended lobar lymph node metastases (Table 2
).
Lobar Lymph Node Metastases According to the Status of Primary
Tumor on Each Side
Although the frequencies of lobar lymph node metastases did not
correlate with histologic type, they were significantly higher in T2 to
T4 cases (40 of 135 patients) than T1 cases (13 of 113 patients;
p = 0.0009), but not were not significantly different between T2
cases and T3 to T4 cases. Of 53 patients with lobar lymph node
metastases, the ratios of extended lobar lymph node metastases were not
affected by histologic type or T classification even on the right side
(Table 3
).
Lobar Lymph Node Metastases According to the Prevalence of Lymph
Node Metastases on Each Side
The frequency of lobar lymph node metastases was significantly
higher in the patients with interlobar/hilar lymph node metastases than
in those without them on the right and left sides (p < 0.0001 and
p = 0.0006, respectively), as well as significantly higher in the
patients with mediastinal lymph node metastases than in those without
them on both sides (p < 0.0001 and p = 0.0003, respectively). On
the right side, extended lobar lymph node metastases were observed in
42.9% of the patients with interlobar/hilar lymph node metastases and
in 34.3% of those with mediastinal ones. Their frequencies were
significantly higher in the patients with interlobar/hilar lymph node
metastases or with mediastinal ones than in those without them
(p < 0.0001, respectively) on the right side. On both sides,
extended lobar lymph node metastases were not observed in the patients
with single-station mediastinal lymph node metastases, unlike in those
with multistation ones (p = 0.0003; Table 4
).
Distribution of Lymph Node Metastases in 16 Patients With Extended
Lobar Lymph Node Metastases
Of eight patients with a tumor in the right middle/lower lobe
associated with lobar lymph node metastases to proximal NPLs, four
patients had no lobar lymph node metastases in the PL. In contrast, of
six patients with a tumor in the right upper/middle lobe associated
with lobar lymph node metastases to retrograde NPLs, all had
lobar lymph node metastases in the PL as well. Of the 14 patients with
right-sided malignancy, interlobar, hilar, and mediastinal lymph node
metastases were all observed in the majority. One patient with a tumor
in the left upper lobe and intrapulmonary metastasis in the lower lobe
had lobar lymph node metastasis in the NPL (Table 5
).
|
Discussion
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The patterns of normal lymphatic flow to the mediastinum have been
summarized by several authors. In general, the normal pulmonary lymph,
including that from the visceral pleura, flows toward the hilum and the
lobar lymph node in the PL,1
6
7
8
9
eventually reaching the
mediastinum2
6
8
10
11
as the main lymphatic route.
Although the patterns of lobar-hilar lymph node metastases of lung
cancer have also been investigated,12
13
14
15
metastases in
all lobar lymph nodes including NPLs have received little
attention.3
In the present study, lobar lymph node
metastases were revealed in 53 of 248 patients (21.4%), the frequency
of which was somewhat lower than that of mediastinal lymph node
metastases but somewhat higher than those of interlobar or hilar lymph
node metastases, as similarly described in previous
reports.12
13
14
15
As we previously reported,16
the frequency of segmental lymph node metastases was higher in the
tumor-bearing segments than in other segments. From the more magnified
viewpoint of the present study, similar findings were obtained; the
frequencies of lobar lymph node metastases in the PL were significantly
higher than those in NPLs in both per-patient and per-lobe analyses.
These results suggest that normal lymphatic flow to the hilum via the
regional lobar lymph node in the PL is fundamentally maintained also in
patients with lung cancer.
Exceptionally, five patients had lobar lymph node metastases limited to
NPLs. Of the five patients, one had intrapulmonary metastases in the
lower lobe (NPL), which might be causative of the lobar lymph node
metastases in the NPL. The other four patients had lobar lymph node
metastases proximal from the level of the PL. Sato et al3
also demonstrated some cases of middle/lower lobe tumors with lobar
lymph node metastasis in the upper lobe but not in the PL. These
findings are probably caused by proximal lymphatic flow along the
bronchial tree as the fundamental route.2
Sixteen of 53 patients with lobar lymph node metastases showed
extension to NPLs in the present study. The extended lobar lymph node
metastases were demonstrated to be not only proximal but also
retrograde. They were observed predominantly on the right side,
especially from the right middle/lower lobe tumors. These findings are
thought to be attributable to the aforementioned proximal lymphatic
flow and the twofold number of lobar lymph nodes in NPLs on the right
side compared with the left-side cases. Although histologic type
and tumor classification did not have a significant influence on the
ratio of extended lobar lymph node metastases, the prevalence of
interlobar/hilar and mediastinal lymph node metastases was
significant. One third of the patients with lobar lymph node metastasis
in the PL, more than one third of those with interlobar/hilar lymph
node metastases, and just over one half of those with multistation
mediastinal lymph node metastases had extended lobar lymph node
metastases on the right side.
Borrie17
and Nohl18
stated that right upper
lobe tumors did not extend below the right middle lobe bronchus;
however, Nohl18
reported an exceptional case with
malignant obstruction. Other authors have reported that malignant
obstruction of the lymphatic channels causes retrograde
spread.10
19
Inhibition of lymphatic flow6
or
widespread proximal lymph node metastases probably induce increased
collateral lymphatic spread at the lobar-hilar lymph node levels
secondary to lymphatic congestion. Other conceivable patterns of
lymphatic spread to the lobar lymph nodes in NPLs are suggested
to be as follows: (1) lymphatic spread to the adjacent lobe from the
primary tumor through an incompletely formed interlobar
space,3
and (2) continuous subpleural lymphatic spread to
the adjacent lobes from the subpleural lymphatics of the
PL.6
Thus, regarding the prevalence of lymph node
metastases, it is surmised that horizontal (collateral) spread
would become more frequent as vertical (proximal) spread progresses
widely.
Formerly, radical pneumonectomy was considered to be the standard
procedure,20
with radical lobectomy subsequently
introduced by Cahan in 1960.21
The former procedure
permits more complete lymphatic dissection theoretically and actually,
judging from our results. Regarding the upper lobar lymph nodes, the
risk of the missed N1 nodes located at the root of the remaining upper
lobe22
and the recommendation of its dissection regardless
of the primary tumor location3
23
have been proposed. We
consider it an efficacious additional procedure to dissect the total
lobar lymph nodes also in remaining NPLs (extended total lobar
lymphadenectomy) for the patients with lobar-hilar or multistation
mediastinal lymph node metastases, especially on the right side.
Although it remains controversial whether the patients with lobar
lymph node metastases in NPLs should undergo
bilobectomy22
or pneumonectomy, such extended lung
resection would be recommended at least for the limited patients with
tumor-positive lobar lymph nodes directly invading the
surrounding tissue of NPLs.
In conclusion, the normal proximal lymphatic flow along the bronchial
tree was predominant and fundamentally maintained as the main drainage
route in lung cancer regardless of the status of the primary tumor
itself. Extended lobar lymph node metastases, which were frequently
observed on the right side, were demonstrated not only in proximal but
also retrograde locations, probably because of lymphatic congestion.
Extended total lobar lymphadenectomy could be recommended for patients
with right lung cancer because of the incidence of metastases in the
NPLs. A follow-up of the patients in this study will be the next
logical step to see whether there is any improvement in survival or
intrathoracic recurrence based on this more radical lymphadenectomy.
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Footnotes
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Abbreviations: NPL = nonprimary lobe;
PL = primary lobe
Received for publication January 3, 2001.
Accepted for publication July 19, 2001.
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References
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TOP
Abstract
Introduction
