Interact CardioVasc Thorac Surg 2008;7:240-243. doi:10.1510/icvts.2007.162701
© 2008 European Association of Cardio-Thoracic Surgery
Institutional report - Thoracic general |
Systemic mediastinal lymph node dissection of right lung cancer: surgical quality control and analysis of mediastinal lymph node metastatic patterns
Nan Wu,
Chao Lv,
Shi Yan,
Hongwei Duan,
Qingfeng Zheng,
Jia Wang,
Hongchao Xiong and
Yue Yang*
Department of Thoracic Surgery, Peking University School of Oncology, Beijing Cancer Hospital and Institute, No. 52, Fucheng Avenue, Haidian District, Beijing 100036, China
Received 4 July 2007;
received in revised form 4 October 2007;
accepted 21 November 2007
 This paper was supported in part by a grant for clinical lung cancer research from Beijing Municipal Educational Committee (2005).
*Corresponding author. Tel./fax: +86-10-88196568.
E-mail address: zlyangyue{at}bjmu.edu.cn (Y. Yang).
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Abstract
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Standardization of systemic mediastinal lymph node dissection (SMLD) of lung cancer requires further investigation. A consecutive 124 right lung cancer patients were recruited for pulmonary resection plus SMLD. Three mediastinal lymph node compartments, (i) the upper compartment (station 1–4), (ii) the middle compartment (station 7–8) and (iii) the lower compartment (station 9), were en bloc collected to achieve surgical quality control and to analyze mediastinal lymph node metastatic patterns. The number of total harvested lymph nodes, N1 nodes and N2 nodes were 21.9±8.7, 9.2±4.7 and 12.8±6.7, respectively. Tumor location (peripheral or central) (P=0.023) and status of blood vessel invasion (P=0.002) were identified as risk factors for nodal involvement. Right upper lobe (RUL) cancer with N2 disease primarily metastasized to the upper compartment (27.3%) (P=0.001). For right lower lobe (RLL) cancer, lymph node metastasis most commonly detected in the middle compartment (48.8%) (P=0.001). Single mediastinal compartment metastasis occurred in 64.7% (11/17) of adenocarcinomas from RUL and RML, whereas multiple compartments metastasis occurred in all adenocarcinoma cases (12/12) from RLL (P=0.001). SMLD needs to standardize the extent of lymphadenectomy and number of removed lymph nodes for surgical quality control. Simplifying mediastinal lymph node stations to three compartments may benefit surgical excision.
Key Words: Right lung cancer; Systemic mediastinal lymph node dissection; Surgical quality control; N2 disease
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1. Introduction
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Surgery is the key modality for the treatment of Stage I–IIIa non-small cell lung cancer (NSCLC). An increasing number of reports support the use of systemic mediastinal lymph node dissection (SMLD) [1, 2]. Complete resection provides accurate staging information, and more importantly, ensures maximal local radical control. However, to standardize SMLD, a consensus, such as adequate extent of lymphadenectomy and the average number of lymph nodes harvested through SMLD, needs to be reached. So far, it is widely accepted that nodal staging can be defined by the removal of at least six lymph nodes from hilar and mediastinal stations. However, it is questionable whether this is powerful enough to define the staging information as accurate as possible. In this study, we addressed surgical procedure and quality control of SMLD. The lymphatic spread pattern of right lung cancer from different lobes and risk factors for nodal metastasis were also summarized.
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2. Materials and methods
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Between September 2003 and November 2006, consecutive 124 patients, diagnosed with right lung cancer, underwent radical resection by the same group of surgeons within our department. Among this group, 80 male patients with a mean age of 59.8±10.0 years and 44 female patients with a mean age of 59.5±10.3 years were enlisted. This study was approved by the Institutional Review Board of Beijing Cancer Hospital and each patient signed informed consent. Preoperative staging methods were applied to all patients, which included chest CT, brain MRI or CT, bone scan and abdominal and supraclavicular ultrasound scanning to rule out potential metastatic lesions or N3 disease. Meanwhile, pulmonary and circulatory functions were required to be eligible for radical resection.
Lobe location of a tumor was defined as the primary site of its origin or the location of the tumor's main body if it involved two lobes. This group was comprised of 66 cases of right upper lobe (RUL) cancer, 15 of right middle lobe (RML) cancer and 43 of right lower lobe (RLL) cancer.
Right mediastinal lymph nodes stations were regrouped as three different compartments and en bloc excision was performed at each compartment. The three compartments included (i) the upper compartment or superior mediastinal node (station 1–4, i.e. stations 1, 2R, 3A, 3P, 4R combined), (ii) the middle compartment or subcarinal and paraesophageal node (station 7–8, i.e. stations 7 and 8 combined) and (iii) the lower compartment or pulmonary ligament node (station 9).
The anterior margin of the upper compartment lay on the superior vena cava (SVC); posteriorly on the trachea; inferiorly above the pulmonary artery; cranially to the angle between the brachiocephalic vein and the trachea (Fig. 1). For the middle compartment, resection started above the upper margin of the inferior pulmonary vein and headed cranially along the superficial layer of pericardium and the esophagus. Finally, the exposure of the left main bronchus, the right main bronchus and the carina was needed (Fig. 2). Fat tissue and lymph nodes within the pulmonary ligament, including the posterior part and lower part were removed as the lower compartment.
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Fig. 1. Two cases (picture a and b) treated with en-bloc lymph node dissection of superior mediastinal lymph nodes (the upper compartment). RBCV, right brachiocephalic vein; RSCA, right subclavian artery; LIV, left innominate vein; SVC, superior vena cava; AV, azygos vein; RPA, right pulmonary artery; RRLN, right recurrent laryngeal nerve; RUL, right upper lobe; RML, right middle lobe; transected RULB, transected right upper lobe bronchus.
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Fig. 2. En-bloc lymph node dissection of the middle compartment in two cases (a and b). RUB, right upper bronchus; RPA, right pulmonary artery; RIPV, right inferior pulmonary vein.
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Metastasis to these compartments, including either to one or multiple node(s) or to one or multiple station(s), was regarded as positive. All tissue samples were sent to the department of pathology for routine examination.
Values were expressed as mean±S.D. (ranges). Statistical analysis was performed using the  2-test (or the Fisher's exact test as required). Multivariate analysis was performed using logistic regression (enter method) to identify factors linked with the status of nodal involvement. A P-value <0.05 was regarded as significant. SPSS V (10.0) was used in this analysis.
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3. Results
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Surgical morbidity and mortality of this group was summarized as Table 1. All patients were treated with standard posterolateral thoracotomy. The most common surgery performed for right lung cancer (72/124, 58%) was lobectomy. Adenocarcinoma (AC) was the major pathological subtype of right lung cancer. A similar distribution of staging among the different lobes was observed.
The numbers of total harvested lymph nodes, N1 nodes and N2 nodes were 21.9±8.7 (ranging from 7 to 40), 9.2±4.7 (ranging from 1 to 23), and 12.8±6.7 (ranging from 1 to 34), respectively. Lymph node metastatic ratio (metastatic lymph nodes number/total lymph nodes number) increased when the disease advanced (data not shown). The main characteristics of nodal involvement are shown in Table 2. Multivariate analysis identified two risk factors for nodal involvement by using logistic regression analysis, which were tumor location (peripheral or central) (OR: 2.823; 95% CI: 1.157–6.891; P=0.023) and status of blood vessel invasion (OR: 11.504; 95% CI: 2.451–54.001; P=0.002).
Fifty cases of N2 disease were diagnosed within this group. The feature of lymph node metastasis to mediastinal compartments was further analyzed based on individual spreading pattern, as shown in Table 3. For RUL cancers, 63.6% (14/22) of cases showed a solely upward spread towards the upper compartment. For RLL cancers, the major direction (57.1%) of mediastinal lymph node metastasis was bifurcated to both the upper compartment and the middle compartment.
Two major types of carcinoma, squamous cell carcinoma (SCC) and adenocarcinoma (AC) were selected to analyze the lymph node spreading pattern that might be affected by histology based on the different lobe location. As shown in Table 4, single N2 compartment metastasis was the main feature of AC either from RUL or RML cancers (8/12 and 3/5, respectively). In contrast, multiple N2 compartments metastasis occurred in all AC cases (12/12, 100%) from RLL. For SCC, there was no significant difference among lobes.
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Table 4 Single/multiple compartments metastasis pattern of N2 disease based on pathology and the lobe location of right lung cancer
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4. Discussion
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SMLD has been reported not to increase morbidity and mortality significantly [1]. Our study also revealed similar results. In this group, the high incidence of atelectasis was probably due to the heavy smoking habits of the patients. Moreover, excess denervation after hilar dissection or carina dissection might contribute to inability to cough.
Gajra et al. [3] and Sawyer et al. [4] all suggested that examining more numbers of lymph nodes would improve the overall survival. Unfortunately, there was no consensus to define the extent of surgery and numbers of lymph nodes that should be dissected. In this study, surgical quality was controlled by following Mountain's thoracic lymph node map. The average number of total lymph nodes collected was 21.9±8.7, including 12.8±6.7 N2 nodes in this study. The total node numbers harvested by other groups were 18.6 in Doddoli's study [5], 17.3 in Lardinois's study [6], and 9.4 in Wu's study [7]. Therefore, more data are required to set the threshold number of lymph nodes dissected for quality evaluation.
According to the mediastinal lymph nodes map, the superior mediastinal lymph nodes are separated artificially by drawing a horizontal line according to anatomical structures. However, during surgery it may be difficult to follow this line. Furthermore, removing lymph nodes by this method might lead to potential tumor cells implantation. Therefore, we propose that the combined evaluation of the upper compartment (stations 1 to 4R) or the middle compartment (stations 7 and 8) should be considered based on the principle of en bloc resection after mobilization of anatomical landmarks. Therefore, under the prerequisite of quality control, a simplified classification of N2 stations could reach the same purpose.
We also analyzed the distribution pattern of different N2 compartments metastasis. These findings agree with those previously reported by Kotoulas et al. [8] and Cerfolio et al. [9]. More interestingly, it seemed that histological types of carcinoma might present different lymphatic spreading pattern when located in different lobes. AC of RLL was more easily spreading to multiple N2 compartments simultaneously, which suggested a more aggressive behavior.
Using logistic regression analysis, we show that central-located cancer (OR: 2.823) and blood vessel invasion (OR: 11.504) were significant predictive factors for nodal involvement. Studies [10] have also shown that central tumors have a higher incidence of lymph node metastases. Special lymphatic draining channels and tumor infiltration capability may be the major contributors. Several papers have examined the prognostic impact of blood vessel invasion [11, 12]. However, to our knowledge, this is the first time that blood vessel invasion has been linked to lymph node metastasis as a risk factor. The significance of these findings is that blood vessel invasion might serve as an independent predictor to assess the nodal status preoperatively.
In conclusion, we propose that it might be feasible to simplify mediastinal lymph nodes into three compartments for the benefit of surgical excision. Besides, the threshold of lymph nodes numbers should be set for quality control.
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Acknowledgements
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We thank Elixigen Co. (Huntington Beach, CA) for proofreading.
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Abstract
1. Introduction
