Eur J Cardiothorac Surg 2007;32:356-361. doi:10.1016/j.ejcts.2007.04.030
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved
Sentinel node sampling limits lymphadenectomy in stage I non-small cell lung cancer
Masashi Muraokaa,*,
Shinji Akaminea,
Tadayuki Okaa,
Tsutomu Tagawaa,
Akihiro Nakamuraa,
Tomoshi Tsuchiyaa,
Tomayoshi Hayashib,
Takeshi Nagayasua
a Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
b Division of Pathology, Nagasaki University Hospital, Nagasaki, Japan
Received 24 February 2007;
received in revised form 16 April 2007;
accepted 18 April 2007.
* Corresponding author. Address: Department of Chest Surgery, Health Insurance Isahaya General Hospital, 24-1 Eishohigashi-machi, Iasahaya-city, Nagasaki 854-8501, Japan. Tel.: +81 957 22 1380; fax: +81 957 22 1184. (Email: mmuraoka{at}lucky.odn.ne.jp).
 |
Abstract
|
|---|
Objective: It is controversial whether a systematic mediastinal lymph node dissection (MLND) needs to be performed in all patients with stage I lung cancer. The present study was done to examine the new sentinel lymph nodes hypothesis based on the lobe of the primary tumor. Methods: In our first study, the lymph node (LN) metastases were assessed in 291 stage I non-small cell lung cancer (NSCLC) patients who had a major lung resection with a systematic mediastinal lymph node dissection. We evaluated the validity of using our new sentinel lymph nodes method based on the lobe of the primary tumor as follows: the pretracheal (#3), tracheobronchial (#4), and hilar nodes (#10) for right upper lobe tumors; #4, subcarinal (#7), and #10 for middle lobe tumors; the subaortic (#5), paraaortic (#6), and #10 for left upper lobe tumors; and the #7, #10, and interlobar nodes (#11) for tumors in either lower lobes. In the second study, we performed a lobectomy with new sentinel node sampling in 64 patients with preoperative complications. If all of the sampling nodes showed no metastases on frozen section diagnosis, systematic node dissections were not performed. Results: Six of 291 patients in the first study had skip metastases that did not involve the new sentinel nodes; 5 of the 6 patients had macroscopic pleural invasion. Thus, we defined pleural invasion as an exclusion criterion for the second study. In the second study, the median follow-up time was 39 months. Metastatic lymph nodes were detected in 11 of 64 patients. Fifty-three patients (83%) had no metastasis in the sampled nodes, and, therefore, a mediastinal lymph node dissection was not done. The morbidity rate in the sampling group was 36%, and there was no mortality. In the sampling group, local recurrences were observed in two patients, distant metastases in eight, and carcinomatous pleuritis in one; the overall 5-year survival rate was 82%. Conclusions: We found that it is possible to perform a less invasive lymphadenectomy for patients with stage I lung cancer using intra-operative sampling of new sentinel lymph nodes.
Key Words: Lung cancer • Diagnosis and staging • Lung cancer surgery • Lymph nodes • Mediastinal lymph nodes
|
1. Introduction
|
|---|
Since the world's population is aging, many thoracic surgeons are now faced with a growing number of patients with resectable lung cancer who have cardiopulmonary dysfunction. Thus, the use of less invasive surgical procedures in these patients and in the elderly must be considered. However, lymph node (LN) metastasis is one of the most important prognostic factors of resectable non-small cell lung cancer (NSCLC) [1,2]. Lobectomy or pneumonectomy with mediastinal lymph node dissection (MLND) has been recommended as the standard radical operation for NSCLC [3]. However, some believe that the incidence of postoperative complications is much higher in patients undergoing MLND than in those not undergoing hilar or MLND [4]. Moreover, there is controversy about whether a systematic MLND needs to be performed in all patients, especially in those with clinical (C-) stage I NSCLC.
Other researchers [5,6] have advocated using the sentinel lymph node (SN) procedure in the same way as it has been used in other organs [7–9]; however, in lung cancer, this procedure is difficult to perform, and no method has been introduced for selective sampling or dissection in lung cancer surgery. We previously investigated the first drainage node of C-stage I NSCLC tumors that had systematic MLND [10]. After this preliminary analysis, we hypothesized that we could predict histological LN metastases by sampling these new sentinel lymph nodes (NSN). We conducted the first study in order to confirm our hypothesis based on the lobe in which the primary tumor was located.
After doing the first study, we prospectively conducted a second study in order to confirm our hypothesis that a less invasive LN dissection, guided by our NSN hypothesis, is a viable alternative for poor risk patients with NSCLC.
|
2. Patients and methods
|
|---|
2.1 The first study
From January 1995 to December 1999, 450 patients with primary lung cancer were treated surgically. Among these patients, 291 patients with C-stage I NSCLC had a major lung resection including lobectomy, bi-lobectomy, or pneumonectomy with systematic MLND (Table 1
). They were examined by enhanced chest computed tomography (CT) scan within 1 month prior to surgery and did not have any swelling over 10 mm in the short-axis diameter either in the mediastinum or in the hilum. Based on the CT finding, none of the tumors involved the chest wall, pericardium, diaphragm, trachea, or esophagus. Preoperatively, distant metastases were not detected on abdominal CT, brain magnetic resonance imaging, or bone scintigraphy.
We hypothesized that the first drainage LNs are at the level of the NSNs, which are defined based on the lobe of the primary tumors as follows: the pretracheal node (#3), tracheobronchial node (#4), or right hilar node (#10) for right upper lobe (RUL) tumors; the #4, subcarinal (#7), or #10 for middle lobe (RML) tumors; the subaortic (Botallo's) node (#5), paraaortic node (#6), or left hilar node (#10) for left upper lobe (LUL) tumors; and the #7, #10, or interlobar node (#11) for tumors in either lower lobes. If the tumor was present in the left lingular segments, #7 was included as an NSN, because some authors have reported solitary metastases at #7 with tumors located in this segment [11,12]. After a histological diagnosis of the permanent section of all of the LNs was done, we retrospectively analyzed the metastatic LN status and evaluated whether selective lymphadenectomy could be done without remnant disease if there were no metastases in the NSN.
2.2 The second study
From January 2000 to June 2003, 64 patients with C-stage I NSCLC who preoperatively had cardiopulmonary dysfunction, complications in other organs, or were elderly patients with a poor performance status, were treated surgically. The characteristics of the 64 patients are shown in Table 2
. The indications for the second study were pulmonary complications (including chronic emphysema in 14, interstitial pneumonia and pulmonary tuberculosis in 4 each, and bronchial asthma and double primary lung cancer in 2 each) in 26; cardiac complications in 8; complications in other organs in 4; and elderly patients, over 70 years of age, with a poor performance status (P.S. 1–3) in 26.
All patients had a lobectomy with NSN sampling. We sampled one node each from the three levels of the NSN for the frozen section. In addition, LN sampling was added if any LN swelling was found during surgery. Experienced staff pathologists examined the LNs macroscopically and then cut them to expose the maximum dimension. The tissue samples were placed in a casing made of plastic and embedded in a medium for freezing. They were then sealed using adhesive aluminum film and frozen with liquid nitrogen. Five-micrometer sections were obtained with a cryostat at –20 °C, placed on a glass slide, fixed in Carnoy's fixing fluid, and stained with hematoxylin and eosin. To increase the reliability of the frozen section diagnosis, the pathologists also examined the imprint cytology specimens fixed with absolute ethanol and stained with HE, or air-dried and Giemsa-stained.
If any metastatic LNs were detected on frozen section during sampling, a systematic MLND was performed. If there were no metastases in any of the LNs sampled, then systematic MLND was not done (sampling group). The survival rate of the patients in the sampling group, including the non-cancer-related deaths, was determined.
In both studies, the lung cancer staging system as defined by the revisions to the international system for staging lung cancer [13] was used. The numbers of the lymph nodes in the mediastinal and bronchopulmonary sites were assigned according to the LN map for lung cancer proposed by Naruke et al. [14].
The institutional review board approved these studies, and written informed consent was obtained from all patients in the second study. Statistical analyses of the data were performed using Stat View software version 5.0 (SAS Institute Inc., Cary, NC, USA). The 
2-test was used to compare the variables. Survival curves were created using the Kaplan–Meier method, and the log-rank test was used to evaluate the curves. The level of significance was set at 5%.
|
3. Results
|
|---|
3.1 The first study
On histology, among the 104 patients with RUL tumors, 10 had p-N2 disease; 8 of these 10 had LN metastasis in at least one or more NSN sites; the other 2 had a solitary metastasis in #1 or #2. Among the 24 patients with RML tumors, 5 had p-N2 disease; all of these patients had metastases in at least one or more NSN sites. Among the 62 patients with right lower lobe (RLL) tumors, 17 had p-N2 disease; all of these patients had metastases in at least one or more NSN sites. Among the 57 patients with LUL tumors, 11 had p-N2 disease; all of these patients had metastases in at least one or more NSN sites. Among the 44 patients with left lower lobe (LLL) tumors, 9 had p-N2 disease; 5 of these 9 had LN metastases in at least one or more NSN sites, while the other 4 had skip metastases in #4, #5, #6, or #9.
In 6 of the 291 patients (2.1%), there were LN metastases that could not be removed from the thoracic cavity by selective LN dissection performed by means of NSN sampling. Table 3
presents an analysis of the histological features of these six patients. Five of the six patients had pleural involvement, which was obvious during surgery (P2 or P3). One patient had a malignant pleural effusion, and another had positive pleural lavage cytology. One patient (Case 7) was diagnosed with a double primary lung cancer (NSCLC and small cell carcinoma). After pleural invasion was ruled out intra-operatively, and lavage cytology was negative, a selective LN dissection with lobectomy for C-stage I NSCLC could be done, except in one patient who had a large cell neuroendocrine carcinoma (LCNEC, Case 6). Therefore, pleural invasion and positive lavage cytology were exclusion criteria in the second study.
View this table:
[in this window]
[in a new window]
|
Table 3 The patients who had lymph node metastasis that could not be removed by selective LN dissection performed by mean of NSN sampling
|
|
3.2 The second study
Fifty-three patients (83%) had no metastases in the nodes that were sampled; in these patients, MLND was not performed. Cancer involvement in the sampling nodes was detected in 11 patients (Table 4
). In 33 patients, 38 extra lymph nodes were sampled due to intra-operative detection of swelling. On frozen section examination, 10 patients had metastases in the NSN and 3 had metastases in other sampling sites, all of which were in the lobar nodes of the upper lobe (#12u). In one patient with an LUL tumor, a metastatic lesion was detected only in #12u (Case 8), and in the other 2 patients, who had RUL (Case 1) and LUL (Case 10) tumors, LN metastases were detected not only in #12u but also in the NSN (#3 and #4 in Case 1 and #5 in Case 10, respectively). In 8 of the 11 patients, a systematic MLND was performed after the sampling. Three of these 11 patients did not undergo MLND due to the presence of severe complications (such as usual interstitial pneumonia and chronic heart failure). These three patients were excluded from the survival rate analysis.
The median follow-up time was 39 months. Seven patients in the sampling group died during follow-up. Three patients died due to lung cancer recurrence; pleural dissemination occurred in one patient and distant metastases in two. Eight patients were alive with recurrences, including two with local recurrences; one patient developed a recurrent tumor in the bronchial stump and the other developed a recurrent tumor in the posterior mediastinum, which could recur in the mediastinal LNs. Both patients received chemo-radiotherapy and are still alive.
The overall survival curve of the sampling group is shown in Fig. 1(a). The 5-year survival rate of the sampling group was 81.9%. The 5-year survival rate of patients with p-stage I or II disease (n
= 43) was 86.3% (Fig. 1(b)), which was significantly higher than in patients with p-stage III or IV disease (n
= 10, p
= 0.0251).
View larger version (16K):
[in this window]
[in a new window]
|
Fig. 1. (a) The overall survival curve of the sampling group. The overall survival curve of the sampling group is shown. The 5-year survival rate of the sampling group was 81.9%. (b) The survival curves of the patients with p-stage I or II and of the patients with p-stage III or IV disease. The 5-year survival rate of the patients with p-stage I or II disease (n
= 43) was 86.3%, which was significantly higher than in patients with p-stage III or IV disease (n
= 10, P
= 0.0251).
|
|
|
4. Comment
|
|---|
Whether MLND needs to be performed in order to improve the prognosis of C-stage I NSCLC has been a controversial subject. Some authors insist that MLND improves survival in patients with stage II and IIIA NSCLC [15], while others have reported that their patients developed complications, including recurrent nerve palsy, chylothorax, and other cardiac complications, probably as a result of MLND [16]. Recently, Allen et al., on the basis of a randomized, prospective trial, reported that complete MLND adds little morbidity to a pulmonary resection done for lung cancer [17]. However, the incidence of chylothorax and recurrent nerve palsy in the MLND group was more than twice as high as in the sampling group. They also reported that MLND had a longer operative time and greater amount of total chest tube drainage. These outcomes indicate that the surgical stress of MLND is greater than that of LN sampling.
We studied 55 patients with C-stage I NSCLC who did not have severe preoperative complications and who had a lobectomy with systematic MLND during the same time period (ND group; Table 5
). Surgical stress parameters were examined in both groups, and the results are shown in Table 6
. Intra-operative hemorrhage in the sampling group was significantly less in the sampling group than in the ND group (p
< 0.01). No blood transfusions were required in the sampling group, but a blood transfusion was required in four ND cases (0% vs 7.3%; P
< 0.05). The morbidity rate in the sampling group was slightly lower than that in the ND group (35.8% vs 49.0%; P
= 0.1641). The incidence of arrhythmia in the sampling group was significantly lower than that in the ND group (7.5% vs 21.8%; P
< 0.05). Tanita et al. insisted that the extent of MLND might affect the incidence of arrhythmia, since the cardiac branches of the vagus nerve are sometimes severed during MLND [4,18]. In the second study, we found that our less invasive LN dissection does not require unnecessary MLND in 83% of patients with stage I NSCLC and thus reduces the incidence of postoperative arrhythmia and decreases intra-operative hemorrhage.
Asamura et al. analyzed the pathology of the LN metastases of 166 patients who had p-N2 disease [11]. They stated that a subcarinal lymphadenectomy was not always required for RUL tumors and for those in the left upper division. Other researchers proposed a selective MLND, in which the dissection of the upper part of the mediastinum was not required for lower lobe tumors with negative hilar and #7 nodes [19]. We previously analyzed 209 patients with C-stage I NSCLC who had a lobectomy or pneumonectomy with systematic MLND [10]. Of the 54 patients with an RUL tumor, 10 patients had p-N2 disease in #3 or #4, without skip metastases in the lower mediastinum. Of the 24 patients with RML tumors, 5 had p-N2 disease in #4 or #7 node. Of the 47 patients with RLL tumors, 10 had p-N2 disease in #7. The other 10 patients had p-N2 disease in #4, #5, or #6 node, and there were no solitary skip metastases in #1–#4, or #7 node in 46 patients with LUL tumors. Of the 38 patients with LLL tumors, 8 had p-N2 disease in #7 or #10. Our results are consistent with previously published results [20]. It could be pointed out that SN in the lobar LN (#12) or in the segmental LN (#13) could not be detected using our methods. However, a complete resection, including the intralobar SN, can be accomplished by doing a lobectomy, even if SN were present in #12 or #13. The most important objective of lung cancer surgery is complete resection of the disease, including metastatic LNs; the detection of SN is not the most important objective.
Disease with macroscopic pleural invasion was an exclusion criterion for selective lymphadenectomy. The relationship between pleural invasion and pathological LN metastasis is shown in Table 7
. The proportion of patients with mediastinal LN involvement (p-N2), who had tumors that had pleural invasion macroscopically and on pathology, was significantly higher than the proportion of patients without pleural invasion (P
= 0.0175 and P
= 0.0007, respectively). Lymph flow from tumors with pleural invasion may go through the thoracic cavity to the mediastinum and induce LN involvement through the direct lymphatic pathway. In the first study, using the exclusion criteria for NSN sampling, the risk of leaving carcinoma behind in the thoracic cavity of patients with C-stage I lung cancer was decreased to 0.3% (1/291).
Only one patient (Case 6) in the first study had solitary LN metastasis (#1). The tumor was diagnosed as an LCNEC, which is well known as a special type of lung carcinoma that frequently shows pathologic features of occult metastasis and has a poor prognosis [22]. Patients with LCNEC should not be considered candidates for selective LN dissection.
The anatomical lymph flow between the lungs and the mediastinum has already been well investigated; four pathways have been identified [23]. Although there are direct pathways from the subpleural lymphatics to the mediastinum [21], most of the lymph flow from the RUL goes to #4 and that from the LUL goes to the pulmonary artery region. The lower bronchial pathway runs along the lower region of the main bronchus (#10) and then reaches the bifurcation nodes (#7), including the crossover pathway. Our NSN selection is quite consistent with these anatomical pathways. Moreover, by excluding patients with tumors invading the pleura or with positive lavage cytology, the metastatic cases with mediastinal involvement can be identified.
Recently, Yoshimasu et al. proposed a limited MLND for NSCLC on the basis of intra-operative histologic examinations [24]. Their goal of achieving a less invasive lymphadenectomy is almost the same as ours; however, the sampling levels in each lobe are different. Using their approach, the efficacy of decreasing surgical stress by limiting the LN dissection appears to be small, since their regional mediastinal LNs spread to both the upper and the lower mediastinum except in the RUL. On the other hand, we omit the dissection of the lower mediastinum in the upper lobe tumors and the dissection of the upper mediastinum in the lower lobe tumors after ruling out metastases in our NSN.
Two problems remain to be solved before our approach can be used for all lung cancer patients who do not have any complications. First, it is unknown whether it is possible to precisely sample the metastatic LNs or whether any metastatic LNs would be left if all of the sampled LNs were found to be negative. It is necessary to prospectively evaluate the precision of LN sampling, since the determination of which LN should be selected for frozen section examination is dependent on the judgment of surgeons.
Secondly, some doubts have been previously expressed about the accuracy of frozen section histology. Montpreville et al. reported that the sensitivity for detecting carcinoma LN metastasis using frozen section diagnosis was 99% (200/202) [25]. We have preliminarily confirmed the accuracy of frozen sections by re-examining the permanent sections in a consecutive series of 210 lymph nodes obtained from 133 lung cancer patients; a false negative was found in only one node (0.5%).
It appears that our selection of NSN on the basis of the lobe of the primary tumors is fully justified, and that, using NSN sampling, a less invasive LN dissection can be performed in poor risk patients with C-stage I NSCLC. However, the accuracy of the frozen sections still needs to be investigated. In addition, a prospective study of LN sampling is needed, since few studies have been done that deal with whether it is possible to perform LN sampling precisely in the selected sites.
|
References
|
|---|
- Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest 1997;111:1718-1723.[Medline]
- Riquet M, Manac’h D, Le Pimpec-Barthes F, Dujon A, Chehab A. Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung. Ann Thorac Surg 1999;67:1572-1576.[Abstract/Free Full Text]
- Naruke T, Goya T, Tsuchiya R, Suemasu K. The importance of surgery to non-small cell carcinoma of lung with mediastinal lymph node metastasis. Ann Thorac Surg 1988;46:603-610.[Abstract]
- Tanita T, Hoshikawa Y, Tabata T, Noda M, Handa M, Kubo H, Chida M, Suzuki S, Ono S, Fujimura S. Functional evaluation for pulmonary resection for lung cancer in octogenarians. Investigation from postoperative complications. Jpn J Thorac Cardiovasc Surg 1999;47:253-261.[Medline]
- Liptay MJ, Masters GA, Winchester DJ, Edelman BL, Garrido BJ, Hirschtritt TR, Perlman RM, Fry WA. Intraoperative radioisotope sentinel lymph node mapping in non-small cell lung cancer. Ann Thorac Surg 2000;70:384-389.[Abstract/Free Full Text]
- Nomori H, Horio H, Naruke T, Orikasa H, Yamazaki K, Suemasu K. Use of technetium-99m tin colloid for sentinel lymph node identification in non-small cell lung cancer. J Thorac Cardiovasc Surg 2002;124:486-492.[Abstract/Free Full Text]
- Tafra L, Lannin DR, Swanson MS, Van Evk JJ, Verbanac KM, Chua AN, Nq PC, Edwards MS, Halliday BE, Henry CA, Sommers LM, Carman CM, Molin MR, Yurko JE, Perry RR, Williams R. Multicenter trial of sentinel node biopsy for breast cancer using both technetium sulfur colloid and isosulfan blue dye. Ann Surg 2001;233:51-59.[CrossRef][Medline]
- Morton DL, Thompson JF, Essner R, Elashoff R, Stem SL, Nieweg OE, Roses DF, Karakousis CP, Mozzillo N, Reintgen D, Wang HJ, Glass EC, Cochran AJ. Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma. Ann Surg 1999;230:453-465.[CrossRef][Medline]
- Kitagawa Y, Fujii H, Mukai M, Kubo A, Kitajima M. Current status and future prospects of sentinel node navigational surgery for gastrointestinal cancers. Ann Surg Oncol 2004:242S-244S.
- Akamine S, Takahashi T, Oka T, Morinaga M, Tagata T, Tagawa Y, Ayabe H. The necessity of lymph node dissection by the analyses of the clinical diagnosis of lymph node metastasis and pathological examination of frozen section. Haigan 1996;39:631(abstract in Japanese).
- Asamura H, Nakayama H, Kondo H, Thuchiya R, Naruke T. Lobe-specific extent of systematic lymph node dissection for non-small cell lung carcinomas according to a retrospective study of metastasis and prognosis. J Thorac Cadiovasc Surg 1999;117:1102-1111.[Abstract/Free Full Text]
- Nishiumi N, Maitani F, Kaga K, Iwasaki M, Nakamura M, Osamura Y, Inoue H. Is it permissible to omit mediastinal dissection for peripheral non-small cell lung cancers with tumor diameters less than 1.5 cm?. Tokai J Exp Clin Med 2000;25:33-37.[Medline]
- Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997;111:1710-1717.[Medline]
- Naruke T, Suemasu K, Ishikawa S. Lymph node mapping and curability at various levels of metastasis in resected lung cancer. J Thorac Cardiovasc Surg 1978;76:832-839.[Abstract]
- Keller SM, Adak S, Wagner H, Johnson DH, For Eastern Cooperative Oncology Group Mediastinal lymph node dissection improves survival in patients with stage II and IIA non-small cell lung cancer. Eastern Cooperative Oncology Group. Ann Thorac Surg 2000;70:358-366.[Abstract/Free Full Text]
- Bollen EC, van Duin CJ, Theunissen PH, vt Hof-Grootenboer BE, Blijham GH. Mediastinal lymph node dissection in resected lung cancer: morbidity and accuracy of staging. Ann Thorac Surg 1993;55:961-966.[Abstract]
- Allen MS, Darling GE, Pechet TT, Mitchell JD, Herdon 2nd JE, Landreneau RJ, Inculet RI, Jones DR, Meyers BF, Harpole DH, Putnam Jr. JB, Rusch VW, ACOSOG Z0030 Study Group Morbidity and mortality of major pulmonary resections in patients of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg 2006;81:1013-1020.[Abstract/Free Full Text]
- Cardinale D, Martinoni A, Cipolla CM, Civelli M, Lamantia G, Fiorentini C, Mezzetti M. Atrial fibrillation after operation for lung cancer: clinical and prognostic significance. Ann Thorac Surg 1999;68:1827-1831.[Abstract/Free Full Text]
- Okada M, Tsubota N, Yoshimura M, Miyamoto Y. Proposal for reasonable mediastinal lymphadenectomy in bronchogenic carcinomas: role of subcarinal nodes in selective dissection. J Thorac Cardiovasc Surg 1998;116:949-953.[Abstract/Free Full Text]
- Kotoulas CS, Foroulis CN, Kostikas K, Konstantinou M, Kalkandi P, Dimadi M, Bouros D, Lioulias A. Involvement of lymphatic metastatic spread in non-small cell lung cancer accordingly to the primary cancer location. Lung Cancer 2004;44:183-191.[CrossRef][Medline]
- Riquet M, Hidden G, Debesse B. Direct lymphatic drainage of lung segments to the mediastinal nodes. J Thorac Cardiovasc Surg 1989;97:623-632.[Abstract]
- Doddoli C, Barlesi F, Chetaille B, Garbe L, Thomas P, Giudicelli R, Fuentes P. Large cell neuroendocrine carcinoma of the lung: an aggressive disease potentially treatable with surgery. Ann Thorac Surg 2004;77:1168-1172.[Abstract/Free Full Text]
- Neef H. Anatomical pathways of lymphatic flow between lung and mediastinum. Ann Ital Chir 1999;LXX(6):857-866.
- Yoshimasu T, Miyoshi S, Oura S, Hirai I, Kokawa Y, Okamura Y. Limited mediastinal lymph node dissection for non-small cell lung cancer according to intraoperative histologic examinations. J Thorac Cardiovasc Surg 2005;130:433-437.[Abstract/Free Full Text]
- Montpreville VT, Dulmet EM, Nashashibi N. Frozen section diagnosis and surgical biopsy of lymph nodes, tumors and pseudotumors of the mediastinum. Eur J Cardiothorac Surg 1998;13:190-195.[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
A. Watanabe, T. Mishina, S. Ohori, T. Koyanagi, S. Nakashima, T. Mawatari, Y. Kurimoto, and T. Higami
Is video-assisted thoracoscopic surgery a feasible approach for clinical N0 and postoperatively pathological N2 non-small cell lung cancer?
Eur. J. Cardiothorac. Surg.,
May 1, 2008;
33(5):
812 - 818.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Muraoka
Reply to Ismail
Eur. J. Cardiothorac. Surg.,
December 1, 2007;
32(6):
949 - 950.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. Ismail
Sentinel node sampling in stage I non-small cell lung cancer
Eur. J. Cardiothorac. Surg.,
December 1, 2007;
32(6):
948 - 949.
[Full Text]
[PDF]
|
|
|
Top
Abstract
1. Introduction
