Is the lymphatic drainage of lung cancer lobe-specific? A surgical appraisal

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1 European Journal of Cardio-Thoracic Surgery 47 (2015) doi: /ejcts/ezu226 Advance Access publication 29 May 2014 ORIGINAL ARTICLE Cite this article as: Riquet M, Rivera C, Pricopi C, Arame A, Mordant P, Foucault C et al. Is the lymphatic drainage of lung cancer lobe-specific? A surgical appraisal. Eur J Cardiothorac Surg 2015;47: a Is the lymphatic drainage of lung cancer lobe-specific? A surgical appraisal Marc Riquet a, *, Caroline Rivera a, Ciprian Pricopi a, Alex Arame a, Pierre Mordant a, Christophe Foucault a, Antoine Dujon b and Françoise Le Pimpec-Barthes a Department of General Thoracic Surgery, Georges Pompidou European Hospital, Paris Descartes University, Paris, France b Department of General Thoracic Surgery, Cedar Surgical Centre, Bois-Guillaume, France * Corresponding author. Department of General Thoracic Surgery, Georges Pompidou European Hospital, 20 rue Leblanc, Paris, France. Tel: ; fax: ; marc.riquet@egp.aphp.fr (M. Riquet). Received 7 January 2014; received in revised form 10 April 2014; accepted 23 April 2014 Abstract OBJECTIVES: Nowadays, early-stage lung cancers are more frequently encountered. Selective lymph node (LN) dissection based on lobespecific lymphatic pathway has been proposed. Our aim was to study nodal involvement according to tumour location. METHODS: We reviewed 1779 lobectomized patients and analysed their pathological characteristics according to tumour location: Group 1 (G1), right upper lobe; Group 2 (G2), right middle lobe; Group 3 (G3), right lower lobe; Group 4 (G4), left upper division; Group 5 (G5), lingula; Group 6 (G6), left lower lobe. The pn status was recorded for each group to analyse the lymphatic spread of non-small-cell lung cancer (NSCLC) according to tumour location. RESULTS: The numbers and proportions of lobectomies in each group were 613 patients in G1 (59.2%), 64 in G2 (6.4%), 359 in G3 (34.6%), 404 in G4 (54.3%), 54 in G5 (7.3%) and 286 in G6 (38.4%). The rates of pn2 involvement were similar, whatever the group was, even when deciphering single- and multistation diseases. on the right side, single-station N2 disease was mainly found in the superior mediastinum (SM) for G1 (95%), and in the inferior for G3 (90%). On the left side, single-station N2 was mainly found in the SM in G4 (94%), and the inferior in G6 (48%). Whatever the side, in case of two-station involvement, both mediastina were concerned in 40% (in G4) to 81% of the case (in G3). Long-term survival rates were different in skip metastasis, single- and multistation involvement, but not between lobes. CONCLUSIONS: Tumour location is not a predictor of nodal metastasis pattern. In surgical treatment of NSCLC, complete systematic mediastinal LN dissection remains the only acceptable procedure from an oncological point of view. Keywords: Lobectomy Lung cancer Lymphatic drainage Lymph node dissection Mediastinum INTRODUCTION Surgical options for the management of mediastinal lymph nodes (LNs) in non-small-cell lung cancer (NSCLC) include LN sampling, complete ipsilateral mediastinal LN dissection (MLND) and ultraradical bilateral MLND through a median sternotomy [1]. Ipsilateral MLND does not improve survival in patients with early-stage NSCLC when compared with sampling [2], but provides more accurate staging and opportunity for adjuvant therapy if occult disease is present. Ipsilateral MLND does not increase mortality or morbidity and remains recommended in patients with resectable NSCLC [2]. However, recent advances in the screening of lung cancer and wider access to imaging facilities have been associated with an earlier diagnosis of NSCLC. In early stages, the idea of tailoring the extent of MLND to each patient and each tumour led to the concept of selective LN dissection (SLND) based on the lobe specificity of the lymphatic spread. SLND has been particularly advocated for patients with advanced age, no apparent LN metastasis and/or impaired pulmonary function [3]. Shimada et al. [3] suggested refraining from resecting LN in the sub-carinal zone in cases of upper lobe tumours, or those of the upper mediastinum in case of lower lobe tumours, supporting the results reported by Asamura et al. [1]. Yoshimasu et al. [4] proposed a SLND according to intraoperative histological examination of three levels of mediastinal LN, primarily defined as sentinel LN mapping. Other studies have found conflicting results. Kudo et al. [5] established that tumour location might contribute in determining the optimal management strategy and accurate prediction of prognosis, whereas Saeteng et al. [6] found the opposite. In this setting, our purpose was to analyse the lymphatic mode of spread of NSCLC according to the tumour location, as disclosed by systematic MLND. The Author Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

2 544 M. Riquet et al. / European Journal of Cardio-Thoracic Surgery PATIENTS AND METHODS The clinical records of 3200 patients who underwent a lobectomy for NSCLC from January 1980 to December 2009 in two French surgical centres were retrospectively reviewed. The data were prospectively entered since April The preoperative work-up included chest X-ray, bronchoscopy, computed tomography (CT) since 1983, spirometry, lung-perfusion scan and a thorough search for metastases (including positron emission tomography (PET) scan since 2004). Mediastinoscopy was performed to exclude N3 disease and to confirm N2 in patients included in various neoadjuvant treatment protocols. Criteria for lung tumours were revised according to the WHO classification [7] and new International Staging System for NSCLC [8]. We focused on patients who underwent standard lobectomy with a complete MLND as described by Martini et al. [9]. Patients with extended lobectomy to adjacent structure, previous history of another cancer, synchronous lung cancer and nodule in another lobe and those who underwent induction therapy were excluded. Patients with sleeve lobectomies (n = 194) and bilobectomies (n = 192) were also excluded. We separately considered left upper division (LUD) segmentectomy and lingulectomy on the left in order to compare them with right upper lobectomy and right middle lobectomy. Tumour locations were classified as Group 1, right upper; 2, middle; 3, right lower lobe (RLL); 4, LUD; 5, lingula and 6, left lower lobe (LLL). The resections were usually performed by postero-lateral thoracotomy, but some lobectomies were performed by video assisted thoracic surgery during the last decade. We analysed the demographic and pathological characteristics of the patients according to the side, lobe and the lymphatic spread considering the pn status of each lobe. The regional LN classification of Mountain and Dresler [10] modified with stations and zones in 2009 [8] was used to define LN stations. The N2 population was divided into a single station [one station involved in the superior mediastinum (SM) (4R or 3 or 4L or 5 or 6) or inferior mediastinum (IM) (7, 8 or 9)] and multiple stations, corresponding to the involvement of two or more of any mentioned stations. The 2R and 4R stations were grouped together because they form the same anatomical LN chain [11]. Continuous variables are described as mean ± standard deviation and compared using the Student s t-test. Categorical variables are described as count and proportion, and compared using the χ 2 test. Follow-up information was obtained from the hospital case records, and a questionnaire completed by the chest physician or general practitioner and from death certificates. Mean follow-up duration was 55.7 ± 64 months: 41.7 ± 53 months for the dead and 132 ± 73 months for the still-alive patients. Actuarial survival curves were estimated by the Kaplan Meier method. Univariate analysis used the following outcome variables: gender, age, type of resection, histology, type of T and N involvement and adjuvant treatments. All data analyses were conducted with the twosided test: a P-value of >0.05 was considered as statistically significant. The statistical software used for the analysis was SEM (Anticancer Centre Jean Perrin, Clermont-Ferrand, France) [12]. The study was approved by our Thoracic Surgery Society Ethic Committee (CERC-SFCTCV), which waived the need for informed consent. RESULTS A total of 1779 patients were reviewed, 1337 males and 442 females, with a mean age of 61.3 ± 10.4 years. Lobectomy was performed on the right in 1035 (58.2%) and on the left in 744 cases (41.8%). Main characteristics of right and left lobectomies are given in Table 1. All studied criteria were similar, whatever the side. The proportion of type of lobectomy was also similar: on the right side, 613 patients in G1-right upper lobe (RUL) (59.2%), 64 in G2-right middle lobe (RML) (6.4%), 359 in G3-RLL (34.6%) versus on the left side, 404 in G4-LUD (54.3%), 54 in G5-lingula (7.3%) and 286 in G6-LLL (38.4%, P = 0.11 for comparison between both sides). The pn status is figured in Tables 2 and 3. On the right side, pn0 was more frequent in the case of RUL, pn1 was more frequent in the case of RLL and the frequency of pn2 was similar in all lobes. On the left side, there was no difference in the frequency of nodal involvement. As compared with the involvement of two or more stations, the frequency of single-station involvement was similar on both sides, but was higher in the case of RUL. The pattern of pn2 distribution in right lobectomy is shown in Table 4. In the case of single-station involvement, N2 was mainly, but not exclusively, found in the SM for RUL (95%), and in the IM for RLL (90%). However, in this group, N2 disease was found in the IM in 5% of RUL and in the SM in 10% of RLL. When two or more stations were involved, both SM and IM were concerned in 73.4% of the cases for RUL and 81% of the cases for RLL. The pattern of pn2 distribution in left lung lobectomy is given in Table 5. In case of single-station involvement, N2 was mainly found in the SM for LUD (94%) and in the IM for LLL (48%). However, N2 disease was found in the IM in 6% of LUD and in the SM in 52% of LLL, the involvement of Station 5 being observed in 13% of cases and the involvement of Station 4L in 39% of cases. When two or more stations were involved, both SM and IM were concerned in 40% of cases for LUD and 76% of case for LLL, with the 4L station being involved in 70.1% of patients. The pattern of LN involvement was slightly different between RML and lingula with less N0 and N2 and more N1 in case of tumour located in the lingula (Tables 2 and 3), but this difference was not significant (P = 0.083). When a single mediastinal station was involved in lingula, metastasis was found in the SM, whereas it was located in the IM in three of four RML. In both lobes, SM and IM were metastatic when two or more stations were involved (Tables 4 and 5). The pattern of pn2 distribution in patients with ct1t2an0 NSCLC is seen in Tables 6 and 7. On the right side, 798 patients underwent a lobectomy for ct1t2an0 NSCLC. There was a N2 involvement in 62 cases (7.7%). Among these, an LN involvement in the other mediastinum was found in 9 cases (14.5% of ct1t2an0 pn2 patients). On the left side, 582 patients underwent a lobectomy for ct1t2an0 disease. There was an N2 LN involvement in 52 cases (8.9%). Among these, an LN involvement was found in the other mediastinum in 15 cases (27.8% of ct1t2an0 pn2 patients). The frequency of unexpected N2 involvement on the left side is mainly explained by LLL NSCLC metastasing to the 4L station. Long-term survival was highly different according to the N status (Fig. 1A). Long-term survival was also significantly different between skip metastasis, single-station and multistation involvement (Fig. 1B). There was no significant difference in long-term survival according to the lobectomy considered, either on the right (Fig. 1C) or on the left side (Fig. 1D). Similarly, there was no significant difference in long-term survival according to the location of the single-station N2 within the mediastinum (P = 0.38), even between Station 5/6 (5-year survival 45%) and Station 4L (5-year survival 20%, P = 0.15). Survival difference according to the

3 M. Riquet et al. / European Journal of Cardio-Thoracic Surgery 545 Table 1: Main characteristics of right and left lobectomies Right Left Total P-value Total 1035 (58.2%) 744 (41.8%) 1779 Male 777 (75.1%) 560 (75.3%) Mean age (years) 60.9 ± ± ,3 ± 10, (57.1%) 156 (42.9%) (56.2%) 310 (43.8%) (60.7%) 278 (39.3%) 708 Smoker 908 (87.7%) 638 (85.8%) Adenocarcinoma 610 (58.9%) 395 (53.5%) Squamous cell 322 (31.1%) 256 (34.4%) 578 Large cell 66 (6.4%) 61 (8.2%) 127 Adenosquamous 27 (2.6%) 23 (3.1%) 50 Other histology 10 (1%) 6 (0.8%) 16 Postoperative death 19 (1.8%) 11 (1.5%) Postoperative complications 242 (23.4%) 164 (22%) Mean size 35.6 ± ± ± pt1: pt1a 220 (21.3%) 138 (18.5%) 358 pt1b 176 (17%) 140 (18.8%) 316 pt2: pt2a 470 (45.4%) 350 (47%) pt2b 101 (9.8%) 62 (8.3%) 163 pt3 63 (6.1%) 53 (7.1%) 116 pt4 5 (0.5%) 1 (0.1%) 6 Visceral pleura involvement 276 (26.7%) 184 (24.7%) N0 754 (72.9%) 505 (67.9%) N1 122 (11.8%) 112 (15.1%) 234 N2 159 (15.4%) 127 (17.1%) 286 Adjuvant treatment Radiation therapy 165 (15.9%) 117 (15.7%) 282 Chemoradiation 110 (10.6%) 79 (10.6%) 189 Chemotherapy 48 (4.6%) 45 (6%) No adjuvant therapy 712 (68.8% 503 (67.6%) 1215 pstage I Stage Ia 301 (29.1%) 200 (26.9%) 501 Stage Ib 323 (31.2%) 219 (29.4%) 542 pstage II Stage IIa 160 (15.5%) 131 (17.6%) Stage IIb 58 (5.6%) 37 (5%) 95 pstage III 150 (14.5%) 130 (17.5%) 280 pstage IV 43 (4.2%) 27 (3.6%) 70 Table 2: pn status in right lobectomies RUL RML RLL Total P-value Total N0 458 (74.7%) 48 (75%) 248 (69.3%) 754 (72.9%) N1 60 (9.8%) 4 (6.3%) 58 (16.2%) 122 (11.8%) N1 intra-lobar 31 (5.1%) 3 (4.7%) 30 (8.4%) 64 (6.2%) 0.66 N1 extra-lobar 29 (4.7%) 1 (1.6%) 28 (7.8%) 58 (5.6%) N2 95 (15.5%) 12 (18.8%) 52 (14.5%) 159 (15.4%) 0.69 N1/2 1 station 46 (7.5%) 2 (3.1%) 15 (4.2%) 63 (6.1%) N0/2 1 station 35 (5.7%) 6 (9.4%) 16 (4.5%) 57 (5.5%) N0/2 2 stations 4 (0.6%) 0 (0%) 4 (1.1%) 8 (0.8%) N1/2 2 stations 10 (1.6%) 4 (6.3%) 17 (4.7%) 31 (3%) N2 1 station 81 (13.2%) 8 (12.5%) 31 (8.7%) 120 (11.6%) N2 2 stations 14 (2.3%) 4 (6.3%) 21 (5.9%) 39 (3.8%) RLL: right lower lobe; RML: right middle lobe; RUL: right upper lobe.

4 546 M. Riquet et al. / European Journal of Cardio-Thoracic Surgery Table 3: pn status in left lobectomies LUD Lingula LLL Total P-value Total N0 282 (69.8%) 38 (70.4%) 185 (64.7%) 505 (67.9%) 0.34 N1 49 (12.1%) 10 (18.5%) 53 (18.5%) 112 (15.1%) N1 intra-lobar 33 (8.2%) 6 (11.1%) 28 (9.8%) 67 (9%) 0.33 N1 extra-lobar 16 (4%) 4 (7.4%) 25 (8.7%) 45 (6%) N2 73 (18.1%) 6 (11.1%) 48 (16.8%) 127 (17.1%) 0.44 N1/2 1 station 32 (7.9%) 2 (3.7%) 18 (6.3%) 52 (7%) 0.10 N0/2 1 station 21 (5.2%) 2 (3.7%) 5 (1.7%) 28 (3.8%) N0/2 2 stations 3 (0.7%) 0 5 (1.7%) 8 (1.1%) N1/2 2 stations 17 (4.2%) 2 (3.7%) 20 (7%) 39 (5.2%) N2 1 station 53 (13.1%) 4 (7.4%) 23 (8%) 80 (10.8%) N2 2 stations 20 (5%) 2 (3.7%) 25 (8.7%) 47 (6.3%) LLL: left lower lobe; LUD: left upper division. Table 4: Pattern of pn2 distribution in right lobectomies RUL RML RLL Total Total N2 95 (15.5%) 12 (18.8%) 52 (14.5%) 159 (15.4%) N2 1 station 81 (85.3%) 8 (66.7%) 31 (59.6%) 120 (11.6%) 2R 4R 75 (92.6%) 2 (25%) 3 (9.7%) 80 (66.7%) 3a 2 (2.5%) (1.7%) 7 4 (4.9%) 6 (75%) 26 (83.9%) 36 (30%) (6.5%) 2 (1.7%) N2 2 stations 14 (14.7%) 4 (25%) 21 (40.4%) 39 (3.8%) 2R 4R + 3a (20%) (7.7%) 2R 4R (60%) 2 (66.7%) 13 (61.9%) 24 (61.5%) 2R 4R + 3a (6.7%) 0 2 (9.5%) 3 (7.7%) (19%) 4 (10.2%) 2R 4R + 3b 1 (6.6%) (2.6%) 2R 4R + 3b (6.7%) (2.6%) 3b (33.3%) 0 1 (2.6%) 2R 4R (9.6%) 2 (5.1%) RLL: right lower lobe; RML: right middle lobe; RUL: right upper lobe. involved lobe, side and N status was not significant when comparing RUL and LUL lobectomies, except in case of N1 patients, with favour on the right side. The median, 5-year and 10-year survivals of patients undergoing an upper lobectomy for N1 disease was 112 months, 58.1 and 46.5% on the right side (n = 60), and 36 months, 39.9 and 29.9% on the left side (n = 49, P = 0.028). DISCUSSION Studying the lobe-specific lymphatic spread of NSCLC from a large surgical series, we found a nodal involvement of the IM in 5% of the RUL and 6% of the LUD, a nodal involvement of the SM in 10% of the RLL and 52% of the LLL, and an involvement of both mediastina in the majority of patients with multistation N2 disease. Three methodological points need specific explanation. Firstly, the number of LN obtained by lymphadenectomy was not provided. We demonstrated in an anatomical study that this number within a mediastinal LN chain was varying from one individual to another [11] and were not able to assign any prognostic impact in a study analysing single-station N2 involvement [13]. Secondly, the study is limited by the number of patients, as 286 patients had N2 disease. However, we think that our classification might avoid methodological bias. Finally, we considered LUD and lingula separately instead of as a single left upper lobe. This was not a contrivance, but rather permitted more pertinent comparisons between both lungs, as already noticed in Gray s Anatomy: the left superior lobar bronchus divides into two bronchi which correspond to the branches of the right principal bronchus as it supplies the right superior and middle lobes [14]. Comparing the different lobectomies, the characteristics and overall long-term survival were similar regardless of the side, as was the frequency of each type of right and left lobectomy. Asamura et al. [1] reviewed 192 N2 patients and Shimada et al. [3]

5 M. Riquet et al. / European Journal of Cardio-Thoracic Surgery 547 Table 5: Pattern of pn2 distribution in left lobectomies LUD Lingula LLL Total Total N2 73 (18.1%) 6 (11.1%) 48 (16.8%) 127 (17.1%) N2 1 station 53 (72.6%) 4 (66.7%) 23 (47.9%) 80 (10.8%) 7 1 (1.9%) 0 9 (39.1%) 10 (12.5%) 9 2 (3.8%) 0 2 (8.7%) 4 (5%) 5 37 (69.8%) 2 (50%) 3 (13%) 42 (52.5%) (50%) 0 2 (2.5%) 4L 13 (24.5%) 0 9 (39.1%) 22 (27.5%) N2 2 stations 20 (5%) 2 (3.7%) 25 (8.7%) 47 (6.3%) (16%) 4 (8.6%) (20%) 0 2 (8%) 6 (12.8%) (5%) (2.1%) L 2 (10%) 2 (100%) 2 (8%) 6 (12.8%) L (8%) 2 (4.2%) 5 + 4L (8%) 2 (4.2%) (10%) (4.2%) 4 + 4L 8 (40%) 0 2 (8%) 10 (21.3%) 4L (5%) (2.1%) 4L+5+6 2(10%) (4.2%) 4L (40%) 10 (21.3%) (4%) 1 (2.1%) LUD: left upper division; LLL: left lower lobe. Table 6: Pattern of pn2 distribution in right lobectomies for ct1t2an0 NSCLC (n = 798) Table 7: Pattern of pn2 distribution in left lobectomies for ct1t2an0 NSCLC (n = 582) RUL RML RLL Total N N2 1ch (85.5%) 4R a N2 2ch (14.5%) 4R + 3a R R NSCLC: non-small-cell lung cancer; RLL: right lower lobe; RML: right middle lobe; RUL: right upper lobe. LUD Lingula LLL Total N N2 1ch L N2 2ch L * 3 7+4L * L L L analysed 207 N2 patients, and both authors reported a similar frequency between both sides, and their results were comparable with ours regarding the frequency of the different lobectomies. We observed that pn2 frequency was similar regardless of the lobes, but pn0 was more frequent in RUL and pn1 in RLL. The rate of pn0 and pn1 according to tumour location has not been widely studied in the medical literature. Yamanaka et al. [15] found a significant difference in the frequency of inter-lobar LN metastases between RUL (1%) and RML/RLL tumours (16%), as reported in our study. These authors also found a significant difference between LUL (6%) and LLL tumours (27%), contrasting to our findings. NSCLC: non-small-cell lung cancer; LUD: left upper division; LLL: left lower lobe. However, both results support that the superior inter-lobar LNs, which can also be involved by metastases from lower lobe tumours, must be dissected routinely regardless of the primary site. Analysing the lymphatic mode of spread, the predominance of a given mediastinum according to the lobe was suggested by Miyoshi et al. in 1997 [16]. These authors found that mediastinal sentinel LN nodeswere2r,3or4rinrul;3,7or8inrll;4l,5or7inluland 4L, 7 or 8 in LLL cancers. More recently, Kotoulasa et al. [17] proposed an even simpler pattern: RUL tumours mainly metastasizing

6 548 M. Riquet et al. / European Journal of Cardio-Thoracic Surgery Figure 1: (A) Survival according to pn involvement. (B) Survival of single-station N0N2 disease (skipping metastases), single-station N1N2 disease and multistation N2 disease. (C) Survival of right lobectomies. (D) Survival of left lobectomies. LLL: left lower lobe; LUD: left upper division; RLL: right lower lobe; RML: right middle lobe; RUL: right upper lobe. to 4R, RML to 4R and 7, RLL to 7; LUL tumours to 5 and LLL to 7 and 9. This assertion has been recently supported by Shapiro et al. [18], who concluded that mediastinal N2 metastases follow predictable lobe-specific patterns in patients with negative preoperative CT scans and PET scans. However, such conclusions conceal that upper lobe tumour may metastasize to the IM and lower lobe tumours to the SM. Accordingly, Asamura et al. [1], Saeteng et al. [6]andManiwa et al. [19] reported that tumour location is not a precise predictor of the pattern of nodal metastasis. Furthermore, both superior and inferior mediastina were even more frequently involved in case of multistation disease, a situation rarely diagnosed during work-up and commonly discovered by surgery. Maniwa et al. even concluded that the recurrence of mediastinal node cancer was significantly greater in patients undergoing lobe-specific systematic nodal dissection than that in those undergoing systematic MLND [19]. For all these reasons, we believe that systematic MLND remains the only option to accurately determine LN status and decrease the rate of mediastinal recurrence. Two specific points require further discussion. Firstly, although the 4L station may be involved from left tumours, it may sometimes be overlooked [17]. Sakao et al. [20] found that it was the next most common metastatic station from LUL cancer, after Stations 5 and 6. We observed that 4L might be involved in 70% of N+ patients with left-sided tumours. Hence, it is mandatory to systematically remove the 4L station when operating on left lung cancer. Secondly, there may be some differences between RML and lingula. Yamanaka et al. [15] noticed that the lymph from the lingula drained via the inter-lobar LN, whereas that from the LUD did not always. Cerfolio and Bryant found that patients with RML cancer were more likely to have N1 disease [21]. We found more N1 in lingula than in RML, but this difference was not significant. Asamura et al. [1] observed that the SM and IM were equally involved in RML tumours; in contrast, the metastastic sites for lingula tumours were Stations 7, 6 and 5. When a single station was metastatic in lingular tumours, metastasis was found in the SM, whereas it was in the IM in three of four RMLs. The overall 5-year survival rate that we observed (30.9%) in N2 patients was similar to that observed by Asamura et al. (35%) [1]. Furthermore, patients with single-station and single-node metastases had a significantly better prognosis than those with more extensive metastases as commonly observed in all series. Contrary to Casalia et al. [22], we observed that skip metastases had a significantly better survival, but that there was no significant difference in survival between lobes either on the right or on the left side. The effect of tumour location on long-term survival after lobectomy for NSCLC remains unclear in the literature. Whitson et al.

7 M. Riquet et al. / European Journal of Cardio-Thoracic Surgery 549 [23] questioned the problem using the Surveillance, Epidemiology and End Results database. They identified patients who underwent lobectomy for pt1/t2 adenocarcinoma or squamous cell carcinomas. There were significant differences in unadjusted overall and cancer-specific survivals based on tumour location. However, after adjusting for patient factors, geographic location of treatment and tumour characteristics, they found that tumour location was not associated with any significant differences in overall survival. CONCLUSION All together, these data suggest that the lymphatic spread of NSCLC cannot be considered as lobe-specific. Therefore, systematic ipsilateral MLND is the only option to accurately determine LNs status, and to obtain both complete resection of the LNs metastasis and interruption of the lymphatic pathways. Conflict of interest: none declared. 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