Ann Thorac Surg 2000;70:1624-1628
© 2000 The Society of Thoracic Surgeons
Original articles: general thoracic
Analyses of segmental lymph node metastases and intrapulmonary metastases of small lung cancer
Akira Yamanaka, MDa,
Takashi Hirai, MDa,
Toshio Fujimoto, MDa,
Yohsuke Ohtake, MDa,
Fumio Konishi, MDb
a Department of Chest Surgery, Fukui Red Cross Hospital, Fukui, Japan
b Department of Pathology, Fukui Red Cross Hospital, Fukui, Japan
Address reprint requests to Dr Yamanaka, Department of Chest Surgery, Fukui Red Cross Hospital, 2-4-1 Tsukimi, Fukui 918-8501, Japan
e-mail: akiray{at}mitene.or.jp
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Abstract
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Background. Curativity and indications for limited resection of small peripheral lung cancer remain controversial.
Methods. Pathologic investigations of segmental lymph node metastases and intrapulmonary metastases in the resected lobe were performed for 94 small peripheral lung cancers (3.0 cm or less in diameter).
Results. Nine patients had segmental lymph node metastases, 1 had intrapulmonary metastases, and 1 had both. Of these 11 patients, 5 had metastases limited to the primary tumor-bearing segments, 2 had metastases in nonprimary tumor-bearing segments, and 4 had metastases in both. Of the 10 patients with segmental lymph node metastases, 7 had metastases in both lobar-hilar and mediastinal lymph nodes, and 3 of 8 with adenocarcinoma had a tumor 2.0 cm or less.
Conclusions. Segmentectomy seems more favorable than wedge resection, but the risk of remnant tumor remains as compared with lobectomy. Evaluation of lobar-hilar or mediastinal lymph nodes is helpful to determine the presence or absence of segmental lymph node metastases. Limited resection can be undertaken with smaller tumors to allow preservation of more lung function while accepting a somewhat enhanced risk of recurrence.
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Introduction
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With the increasing incidence of adenocarcinoma and progress in roentgenologic imaging technique, resection of small peripheral lung cancer has been performed more often. Lobectomy is the main surgical procedure for lung cancer, with limited resection remaining controversial in terms of curativity compared with lobectomy. In the present study, we evaluated segmental lymph node metastases and intrapulmonary metastases in each resected lobe with small peripheral lung cancer.
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Patients and methods
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Patient eligibility
From 1989 through July 1999, 305 patients underwent pulmonary resection for lung cancer in our hospital. Of this group, we reviewed the 94 consecutive cases of small peripheral lung cancer. Finally, patients were selected according to the following tumors or conditions for this study: (1) non–small cell lung cancer (NSCLC); (2) 3.0 cm or less in diameter of primary tumor; (3) peripheral tumor originating at more peripheral sites of the lung from the segmental lymph nodes; (4) localization of whole primary tumor limited within one lobe; (5) lobectomy performed as for the primary lobe; (6) total dissection of the regional lymph nodes (lobar, hilar, and mediastinal system); (7) no preoperative chemotherapy or radiotherapy; and (8) exclusion of patients with synchronous double primary lung cancer or with stage IV. All patients were staged according to the new International Staging System for Lung Cancer [1, 2].
Ages ranged from 30 to 84 years with a mean of 64.4 ± 9.3 years. There were 53 men and 41 women, a ratio of 1.29:1. All patients had a physical examination, chest roentgenogram, bronchoscopy, whole-body computed tomography, brain computed tomography or magnetic resonance imaging, and bone scanning. Sixty tumors were located in the right lung, and 34 in the left. The tumors were histologically classified as adenocarcinoma in 67 cases, squamous cell carcinoma in 22, and large cell carcinoma in 5. There were 62 patients with stage IA, 3 with stage IB, 9 with stage IIA, 13 with stage IIIA, and 7 with stage IIIB (Table 1). Of all patients, 26 had metastases to the lobar-hilar (patient nos. 10 to 12) or mediastinal lymph nodes. Each T2 case was classified as such because of exposure of tumor on the pleural surface (p2) although smaller than 3.0 cm in diameter, and each T4 case was classified because of pleural dissemination or intrapulmonary metastasis within the same lobe.
Pathologic assessment
All resected lobes were investigated as follows before fixation by endobronchial formalin instillation. The lung parenchyma was torn off the bronchial wall in a peripheral direction from the lobar bronchus, and at least the subsegmental bronchial generation was naked. Simultaneously, the lobar and segmental lymph nodes were resected for histopathologic examinations. The locations of primary tumor-bearing segments (TBSs) were tenderly and precisely investigated using an endobronchial probe. The TBSs were easy to recognize because the proximal bronchi were already naked. Then, the resected lobe was fixed by endobronchial formalin instillation, and simultaneously the central lung parenchyma that was removed from the segmental and subsegmental bronchial wall was restored to its original place. The specimen was cut into slices 1.0 cm thick and examined for intrapulmonary metastases macroscopically and histopathologically. All the resected specimens in addition to hilar and mediastinal lymph nodes were transported to the laboratory for histopathologic investigation. As for segmental lymph nodes, direct extension with primary tumor was excluded from the category of metastases [2]. Lymph node metastases were marked using the mapping of the American Thoracic Society [3].
Statistical analysis
All statistical analyses were performed using a software package (StatView 4.5, Abacus Concepts, Inc, Berkeley, CA). To compare the frequencies of the various categorical outcomes in the two groups, data were evaluated by two-by-two contingency 
2 with Yates’s correction for continuity or Fischer’s exact test when the sample size was small.
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Results
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Tumor size and the number of tumor-bearing segments and nonprimary tumor-bearing segments
The total number of TBSs in the 94 patients was 119. There were 21 patients (22.4%) with multiple TBSs. The mean number of TBSs per patient was 1.27. Of 40 patients with a tumor 2.0 cm or less in diameter, there were 38 patients (95.0%) with a single TBS, and the mean number of TBSs per patient was 1.05. Of 54 patients with a tumor 2.1 to 3.0 cm in diameter, there were 35 patients (64.8%) with a single TBS, and the mean number of TBSs per patient was 1.43. The incidence of multiple TBSs (19 of 54) in the patients with a tumor 2.1 to 3.0 cm in diameter was higher than that (2 of 40) in the patients with a tumor 2.0 cm or less in diameter (p = 0.0013). The total number of resected segments in the 94 patients was 344 (Table 1). The total number of nonprimary TBSs (NTBSs) in the 94 patients was 225. There were 15 patients (16.0%) with no or a single NTBS. The mean number of NTBSs per patient was 2.39. Even in the 40 patients with a tumor 2.0 cm or less in diameter, 4 (10.0%) had no or only a single NTBS. In contrast, in the 54 patients with a tumor 2.1 to 3.0 cm in diameter, 11 (20.4%) had no or only a single residual NTBS. Except for the cases undergoing right middle lobectomy, all of the 36 patients with a tumor 2.0 cm or less in diameter had two or more NTBSs, but 7 (14.0%) of 50 patients with a tumor 2.1 to 3.0 cm had no or only a single NTBS (Table 2).
Lymph node metastases and intrapulmonary metastases in each number of tumor-bearing segments
There was no correlation between the number of TBSs and segmental lymph node metastases, intrapulmonary metastases, and lobar lymph node metastases (single TBS versus multiple TBSs) (p = 0.4507; Table 3).
Segmental and lobar lymph node metastases and intrapulmonary metastases in each tumor size
Ten patients (10.6%) had segmental lymph node metastases (total 16 lymph nodes). Three of these 10 patients showed T4 (dissemination or intrapulmonary metastasis) as their T factor. Segmental lymph node metastases were limited to TBSs (total six lymph nodes) in 6 patients, limited to NTBSs (total one lymph node) in 1, and consisted of both TBSs (total three lymph nodes) and NTBSs (total six lymph nodes) in 3. As for segmental lymph node metastases in TBSs, each was a single metastasis. In 2 patients (2.1%), intrapulmonary metastases were detected and consisted of a single lesion of adenocarcinoma and large cell carcinoma, respectively, in NTBSs. One of these 2 patients with intrapulmonary metastases had concurrent segmental lymph node metastasis as well (Table 4). Of 10 patients (total 36 resected segments) with segmental lymph node metastases, the incidence of segmental lymph node metastases in TBSs (9 of 11) was higher than that in NTBSs (7 of 25) (p = 0.0042). Of 40 patients with a tumor 2.0 cm or less in diameter, 2 (5.0%) had intrapulmonary metastases or segmental lymph node metastases in NTBSs. In contrast, of 54 patients with a tumor 2.1 to 3.0 cm in diameter, 4 (7.4%) had intrapulmonary metastases or segmental lymph node metastases in NTBSs. Four (40.0%) of 10 patients with lobar lymph node metastases had segmental lymph node metastases or intrapulmonary metastases. Seven of 10 patients with segmental lymph node metastases also had metastases both in lobar-hilar and mediastinal lymph nodes.
Segmental lymph node metastases and intrapulmonary metastases in each tumor size of adenocarcinoma and squamous cell carcinoma
Of 67 patients with adenocarcinoma, 7 had segmental lymph node metastases and 1 had both segmental lymph node metastasis and intrapulmonary metastasis. Of these 8 patients (11.9%), 7 (10.4%) had metastases in N2 site, and 4 (6.0%) had segmental lymph node metastases in NTBSs or intrapulmonary metastasis. Of 32 patients with a tumor 2.0 cm or less in diameter, 3 (9.4%) had segmental lymph node metastases. In contrast, of 35 patients with a tumor 2.1 to 3.0 cm in diameter, 5 (14.3%) had segmental lymph node metastases or intrapulmonary metastases. There was no correlation between the tumor size and segmental lymph node metastases including intrapulmonary metastases in adenocarcinoma. Of 22 patients with squamous cell carcinoma, 2 (9.1%) had segmental lymph node metastases (Table 5). In 5 patients with a tumor 2.0 cm or less in diameter, lymph node metastases or intrapulmonary metastases were not observed at all.
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Table 5. Segmental Lymph Node Metastases and Intrapulmonary Metastases in Each Tumor Size of Adenocarcinoma and Squamous Cell Carcinoma
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Comment
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Lobectomy remains the main surgical procedure, whereas limited resection with curative intent is controversial in terms of curativity as compared with lobectomy, and the indications for limited resection for small peripheral lung cancer are still controversial. There have been some reports that evaluate the postoperative locoregional recurrence or survival between limited resection and lobectomy. Read and colleagues [4], Pastorino and associates [5], and Kodama and coworkers [6] reported that locoregional recurrences in limited resection were not more frequent, but their studies were not equally distributed in era or were not randomized with respect to patient selection or tumor size. Other authors [7–9] stated that the locoregional recurrence rates were higher in limited resection. Warren and Faber [7] and Ginsberg and Rubinstein [8] reported that locoregional recurrence incidences in limited resection for peripheral T1 N0 tumor were higher than in lobectomy.
This article presents the pathologic metastatic findings in resected lobes and evaluation for the curativity in limited resection as well. The patients evaluated here were consecutive, and pathologic investigation for resected specimens was prospectively performed. Clinical characteristics of the patients, as previously mentioned in small peripheral lung cancer, included a similar incidence of lymph node metastases, predominance of adenocarcinoma histologically, right side upper lobe as location, and T1 N0 as stage [10, 11].
There were 73 (77.6%) single TBSs and 21 (22.4%) multiple TBSs, the rates of which were compatible with those of single and multiple segmentectomy cases reported by Read and colleagues [4]. There was no correlation between the number of TBSs and the incidence of segmental lymph node metastases including intrapulmonary metastases. With increasing size of tumor, the number of TBSs had a tendency to increase, and the proportion of patients with no or only a single NTBS increased. Segmentectomy seems to be not acceptable for one seventh of patients with a tumor 2.1 to 3.0 cm in diameter. Our findings suggest that segmentectomy would be more suitable for smaller tumor than for larger ones, because of the ability to obtain enough resection margins and the large number of NTBSs.
The incidence of segmental lymph node metastases (10.6%) was rather higher compared with other reports [10, 12, 13]. The incidence of intrapulmonary metastases (2.1%) was low, as similarly described by some authors [10, 14, 15] but unlike another [16]. Intrapulmonary metastases in the same lobe were included in the present study because of the possibility of local metastatic manifestation [10, 14]. The incidence of metastases to segmental lymph node in TBSs was higher than that in NTBSs, as had been expected. Of 11 patients with segmental lymph node metastases or intrapulmonary metastases, 5 had metastases limited to TBSs, 4 had metastases to both TBSs and NTBSs, and 2 had metastases to NTBSs alone. From the viewpoint of segmental lymph node metastases and intrapulmonary metastases, it is suggested that 6 patients (6.4%) would have remnant tumors for certain in the same lobe if segmentectomy was performed, and that 11 patients (11.7%) would have remnant tumors for certain in the same lobe if wedge resection was performed. As for the estimation of segmental lymph node metastases, intraoperative evaluation of lobar lymph nodes alone would be insufficient. Complete evaluation of lobar-hilar or mediastinal lymph nodes would be helpful to estimate segmental lymph node metastases and to avoid the risk of remnant tumor by alteration of the operative procedure from limited resection to lobectomy, as similarly shown by Takizawa and colleagues [12, 13]. If the intraoperative evaluations for metastases in lobar-hilar and mediastinal lymph nodes are completely performed and node-positive patients (26 patients) are excluded from the indication of limited operation, 1 patient (1.5%) would still have remnant tumors by segmentectomy, and 2 (2.9%) would have remnant tumors by wedge resection.
These findings were confirmed by some previous authors’ descriptions, such as incomplete resection [7], failure to resect intrapulmonary microscopic and lymphatic spread [8], or unremoved microscopic metastases in lobar and segmental lymph nodes [12]. Thus, limited resection seems to confer a higher risk of local recurrence compared with lobectomy, whereas segmentectomy seems to be more preferable than wedge resection for patients with a tumor 3.0 cm or less, as mentioned by some investigators [4, 8]. Our findings seem to confirm the operative outcome showed by some investigators. Ginsberg and Rubinstein [8] reported that locoregional recurrence rates showed a threefold increase with wedge resection and 2.4-fold increase with segmental resection compared with lobectomy in a randomized trial of lobectomy versus limited resection in a study that was limited to patients with T1 N0 tumor. Warren and Faber [7] stated that the locoregional recurrence rate was increased 3.5-fold or more by segmentectomy compared with lobectomy in patients with T1 N0 tumor.
The incidence of segmental lymph node metastases or intrapulmonary metastases does not always correlate with the tumor size, especially in adenocarcinoma. These findings also confirmed the lack of any correlation between the size of tumor and the risk of locoregional recurrence developing, as shown by Warren and Faber [7]. In fact, even limited to the patients with a tumor 2.0 cm or less, N1 to N2 cases occurred frequently [10, 12, 16, 17], and recurrence in the mediastinum after limited operation was also observed [6]. Even in small peripheral lung cancer, aggressive intraoperative pathologic examinations on lymph nodes around the hilum and mediastinum are required [4, 9, 18]. Furthermore, as intraoperative identification of the lymph node metastases is not always complete [16, 18] and is unreliable and difficult by surgical evaluation [12, 13], mediastinal dissections may also be mandatory [6, 10–12, 16], especially in adenocarcinoma [12].
The risk of local recurrence was considered to be somewhat lower (but not significant) in patients with squamous cell carcinoma, both with segmentectomy and wedge resection, as compared with adenocarcinoma. Koike and coworkers [15] reported that the rates of lymph node metastasis and intrapulmonary metastasis of squamous cell carcinoma were lower than those of adenocarcinoma. As Asamura and colleagues [10] mentioned, limited resection may be indicated in squamous cell carcinoma with a tumor 2.0 cm or less in diameter without intraoperative evaluation of lymph node metastases.
In conclusion, segmentectomy seems more favorable than wedge resection as a limited operation with curative intent, but still has the risk of locoregional recurrence compared with lobectomy. As regards the criteria for limited resection, tumor size alone is not adequate, and the specific radiographic findings based on pathology are also required. Evaluation of lobar-hilar or mediastinal lymph node metastases is helpful in deciding the suitability of limited resection and will identify almost all cases with intrapulmonary lymph node metastases. Although even smaller tumors have some risk of remnant metastatic tumor, this method has the advantage of preserving more lung function and keeping adequate resection margins when limited resection is performed.
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Accepted for publication April 14, 2000.
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Abstract
Introduction
