|Year : 2013 | Volume
| Issue : 5 | Page : 101-105
Comparison of lobe-specific mediastinal lymphadenectomy versus systematic mediastinal lymphadenectomy for clinical stage T 1a N 0 M 0 non-small cell lung cancer
Wei Ma1, Zhen-Jiang Zhang2, Yun Li1, Guo-Yuan Ma1, Lin Zhang1
1 Department of General Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Province, 250021, China
2 Department of General Thoracic Surgery, The People's Hospital of Weifang municipalities, Shandong Province, 250021, China
|Date of Web Publication||30-Sep-2013|
Department of General Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University
Source of Support: None, Conflict of Interest: None
Objective: This study was to explore the appropriate extent of mediastinal lymph node dissection for clinical stage T 1a N 0 M 0 non-small cell lung cancer (NSCLC) by comparison between two modes of mediastinal lymph node dissection.
Materials and Methods: A total of 96 clinical stage T 1a N 0 M 0 NSCLC cases received radical surgery were randomly divided to lobe-specific mediastinal lymphadenectomy (LL) group and systematic mediastinal lymphadenectomy (SL) group from the year 2004 to 2008. The effects of SL and LL on morbidity, N staging, overall survival (OS) and disease-free survival (DFS) were investigated. Meanwhile, associations between clinicopathological parameters and metastasis of lymph nodes were analyzed.
Results: The mean operating time and blood loss in LL group were significantly less than that in the SL group (135.48 ± 25.44 min vs. 180.85 ± 39.36 min, 155.11 ± 25.17 ml vs. 161.32 ± 28.20 ml, P < 0.05), the mean numbers of dissected lymph nodes of the SL group was significantly greater than that in the LL group (17.1 ± 3.7 vs. 9.4 ± 2.1, P < 0.05). The post-operative overall morbidity rate was higher in the SL group than that in the LL group (P < 0.05). There were no significant difference in migration of N staging, OS and DFS between two groups. The post-operative N staging, the tumor cells differentiation and the ratio of ground glass opacity (GGO) in tumor were the independent factors influencing long-term survival. Moreover, the significant correlation was seen between the metastasis of lymph nodes and clinicopathological parameters including tumor location and the GGO ratio.
Conclusion: The LL group had similar efficacy as the SL group in the clinical stage T 1a N 0 M 0 NSCLC and there was unnecessary to perform systematic lymphadenectomy in such patients with a high ratio of GGO.
Keywords: Ground glass opacity, lobe-specific mediastinal lymphadenectomy, non-small cell lung cancer, systematic mediastinal lymphadenectomy
|How to cite this article:|
Ma W, Zhang ZJ, Li Y, Ma GY, Zhang L. Comparison of lobe-specific mediastinal lymphadenectomy versus systematic mediastinal lymphadenectomy for clinical stage T 1a N 0 M 0 non-small cell lung cancer. J Can Res Ther 2013;9, Suppl S1:101-5
|How to cite this URL:|
Ma W, Zhang ZJ, Li Y, Ma GY, Zhang L. Comparison of lobe-specific mediastinal lymphadenectomy versus systematic mediastinal lymphadenectomy for clinical stage T 1a N 0 M 0 non-small cell lung cancer. J Can Res Ther [serial online] 2013 [cited 2020 Feb 28];9:101-5. Available from: http://www.cancerjournal.net/text.asp?2013/9/5/101/119119
FNx01Co-author: Wei Ma and Zheng-Jiang Zhang have the equal work
| > Introduction|| |
The peripheral lung cancer, which diameter less than 2 cm was found more and more commonly in clinical practice. The latest tumor, lymph nodes, and metastasis (TNM) staging of lung cancer proclaimed by International Association for the Study of Lung Cancer in 2009 that the tumor, which maximum diameter ≤2 cm and no invasion of the visceral pleura and main bronchus is specifically defined as T1a cancer in non-small cell lung cancer (NSCLC).  T 1a NSCLC is the clinical type, which has the most promising prognosis by operation, but the necessary of systematic lymph node dissection has been widespreadly disputed. We designed this study to elucidate the influence of the extent of lymph node dissection and to explore the factors influencing lymph node metastasis.
| > Materials and Methods|| |
The present study protocol was approved by the ethical committee at Shandong Provincial Hospital Affiliated to Shandong University.
| > Clinical Materials|| |
According to the inclusion criteria in the study, 96 pre-operative cases (40 men and 56 women with a median age of 56.5 years; range, 37-82 years) all received bone electroconvulsive therapy- the electrical capacitance tomography, cerebral magnetic resonance, chest plus upper abdominal enhanced computed tomography (CT) scan the before surgery, the relevant examinations mentioned above indicated all of the tumors size ≤2 cm and no apparent enlargement of intrathoracic lymph nodes (size ≤1 cm) and no evidence of distant metastasis, from which we determined all the cases clinical stage cT 1a N 0 M NSCLC [Table 1]. All the cases were randomly divided into two groups: A systematic mediastinal lymphadenectomy (SL) group and a lobe-specific mediastinal lymphadenectomy (LL) group.
|Table 1: Associations between clinicopathological characteristics and prognosis|
Click here to view
The lymph node dissection were based on the distribution map of lymph node named by Naruke about lung cancer.  The extent of lymph nodes dissection for different lobes of the lung in the (LL) group were as the following: Right upper lobar tumor (Station No. 4 and No. 7) and left upper lobar tumor (Station No. 5 and No. 7) and right and left middle or lower lobar tumor (Station No. 7 and No. 9).
The indicators including clinical features, operating time, blood loss, the volume of thoracic drainage, hospital days, post-operative complications, pathologic type and staging, pathological staging, the number of lymph node dissection and overall survival (OS) were investigated. In addition, focal ground glass opacity (GGO) was defined as focal GGO high-density shadow of lung on the thin-section CT scans. The cases were divided to the high proportion group and low proportion group on the basis of 50%.
Post-operative follow-up was performed for at least 5 years for all patients and the deadline was in June 2013.
The Pearson χ2 test and linear correlation analysis were used for classified variable (or the Fisher's exact test as n < 40). The t-test was used for comparisons of the sample mean. Survival rate was calculated by Kaplan-Meier method and analyzed with the log-rank test. The P < 0.05 was considered to be significant. The SPSS 17.0 software package was used for all statistical analysis. The cases that were lost or dead from surgery and tumor-free were analyzed as censored data according to request of statistical analyses.
| > Results|| |
Comparison of relative indicators
No surgical deaths were reported in the study group. As is seen in [Table 2], the average operating time, blood loss and postoperative thoracic drainage in LL group were significantly lower than that in the SL group, but there was no significant difference in hospital days between two groups. As is seen in [Table 3], the incidence of post-operative complication in LL group was significantly lower than that in the SL group.
Comparisons of lymph node staging
The mean numbers of dissected lymph nodes in the SL group was significantly more than that in the LL group (17.1 ± 3.7 vs. 9.4 ± 2.1, P < 0.05). However, There was no significant difference in migration of N staging between the two groups (P > 0.05), The post-operative pathological stage showed 70 cases I A , 6 cases I B , 7 cases II A and 13 cases βA according to the latest international TNM staging of lung cancer [Table 4].
Comparisons of postoperative survival
During the follow-up period, recurrence and metastasis occurred in 38 cases, simultaneously 31 cases died of the diseases related to tumor. As the prognostic analysis showed, there were no significant difference in OS and disease-free survival (DFS) between LL group and SL group. In addition, it prompted a bad post-operative prognosis if there were metastasis of mediastinal lymph nodes in clinical stage T 1a N 0 M 0 NSCLC, low degree of differentiation and low ratio of GGO. Those with high ratio of GGO had no recurrence during the follow-up 5 years.
Associations between clinicopathological parameters and metastasis of mediastinal lymph nodes
The significant correlation was seen between the metastasis of mediastinal lymph nodes and clinicopathological parameters, including location and the ratio of GGO in tumor in two groups (P < 0.05). Moreover, metastasis of mediastinal lymph nodes was not observed in the patients with high ratio of GGO [Table 5].
|Table 5: Associations between clinicopathological parameters and metastasis of mediastinal lymph nodes in SL group|
Click here to view
| > Discussion|| |
The latest TNM staging of lung cancer was proclaimed in 2009, which emphasized the impact of the size of tumor on prognosis. T 1a N 0 M 0 NSCLC is the earliest stage having the best post-operative prognosis. Undoubtedly, surgery is the best method to T 1a N 0 M 0 NSCLC. However, whether SL procedure remained in dispute. Wu yilong reported that SL was conducive for accurate staging of lung cancer and improving survival rates, especially in early-stage lung cancer. Meanwhile, some experts have declared that SL not only could not promote prognosis of early lung cancer, but also increases the occurrence of post-operative complications and the trauma of patients and suggested that the selected lymph node dissection or sampling should be performed. ,,,
The concept of Lobe-specific mediastinal lymph node dissection was first proposed by the European Association of Thoracic Surgeons.  It refers to dissecting the mediastinal tissues in specific area including lymph nodes, according to the location of primary tumor in different lobes. As it not only avoids the sampling drawback of missing occult lymph node metastasis, but also reduces the range of dissection, which made some scholars advocate Lobe-specific lymph node dissection in early-stage lung cancer surgery as a better choice. However, now there is not a consensus on the range of specific lymph nodes dissection in domestic and overseas.
From our study, the extent we suggested was station 4 th and 7 th lymph node for the right upper lobe tumors, 5 th and 7 th lymph nodes for the left upper lobe and 7 th and 9 th lymph nodes for left lower lobe and the right middle/lower lobe. Previous studies showed the rate of mediastinal lymph node metastasis in early-stage NSCLC was only about 10%. , In our study, only seven cases of the 51 cases in SL group occurred mediastinal lymph node metastasis (13.7%). This founding suggests that T1a NSCLC grow locally primarily and scarcely invade the lymphatic system, NSCLC metastasizes mostly to the regional lymph nodes, the tumors in upper lobe transfer to the upper mediastinum lymph nodes and those in the lower and middle lobe transfer to lower mediastinum lymph nodes. This provided us great support for lobe-specific dissection. As is proved, the 7 th lymph node is a crossing point of thoracic visceral lymphatic drainage, so no matter where the tumors are, our study emphasizes the dissection of 7 th lymph nodes. In addition, to avoid the overkill to the natural immune barrier-lymphatic network, the 4 th , 5 th , 9 th should be dissected respectively according to the tumors location in the lobe.
As is reported, SL can cause potential postoperative complications such as the injury of recurrent laryngeal nerve, chylothorax and bronchial stump fistula. In addition, lymph nodes have an important defensive function and SL can cause reduction of local immune function so that local recurrence or distant metastasis of the tumor may occur.  Therefore, SL cannot more benefit than LL. Our study found that LL group has a significant advantage in shortening the time of operation, decreasing blood loss and reducing the incidence of post-operative complications compared with SL group. In addition, the analysis of prognosis showed that SL group did not have a greater advantage than the LL group on survival. Some scholars advocated systematic lymph nodes dissection should be done to provide an accurate postoperative N stage. However, our study suggested that there was no significant difference in post-operative N stage. Of course, we cannot deny that lobe-specific dissection may omit some metastasized lymph nodes in higher site in a few patients, even if SL is done, the prognosis cannot be better usually. Therefore, lobe-specific dissection can be a better choice for lymph node dissection for T1a NSCLC. ,
In addition, our study showed that the cases with high proportion of GGO had no recurrence and the prognosis is good during the five years' follow-up. A further analysis of the cases in SL group showed that none of the 16 cases with high proportion of GGO had mediastinal lymph node metastases. This result might be because of the shortness of cases, but it was similar to previous reports. , In HRCT, the present of GGO mostly indicated the probability of focal alveolar cell carcinoma.  Some studies showed that the increase of BAC component in adenocarcinoma may indicate a better prognosis. A more BAC component in the tumor meant a lighter degree of invasion and a smaller probability of metastasis of tumor and lymph nodes. Some scholars have even advocated a localized segmentectomy or a wedge resection instead of the standard lobectomy plus lymph node dissection for cases with high GGO.  In addition, our study also found that the closer the tumor lied to the hilum, the easier mediastinal lymph node metastasis occurs. In our opinion, as there is no patient can be absolutely excluded the presence of N2 currently, a sentinel frozen biopsy can be conducted during the operation of T1a NSCLC. And if the rapid pathology is negative, patients with high GGO component need not have a systematic mediastinal lymph node dissection.
The number of cases in this study was small and the conclusion still need to be demonstrated by large sample studies. Recently, Darling  published a randomized controlled study on the pattern of lymph node dissection of early-stage NSCLC, which enlisted about 1,111 cases with a follow-up duration more than 6 years. All cases were performed lymph node sampling and sent for rapid pathology. The cases, which were proved without lymph node metastasis by pathology, were randomly grouped for mediastinal lymph node sampling and dissection. The post-operative analysis showed that the survival rate, the local recurrence rate and mortality rates had no statistical difference in the two groups [Figure 1] and [Figure 2]. Therefore, a selected mediastinal lymph node sampling or biopsy of sentinel lymph node during the operation was significant for mediastinal lymph nodes dissection and it presented a new strategy for whether the lymph nodes dissection should be performed in T1a NSCLC.
| > References|| |
|1.||Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest 2009;136:260-71. |
|2.||Asamura H, Nakayama H, Kondo H, Tsuchiya 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 Cardiovasc Surg 1999;117:1102-11. |
|3.||Yang F, Wang J. Role of surgery for stage IIIA-N2 non-small cell lung cancer. Thorac Cancer 2011;2:90-4. |
|4.||Okada M, Sakamoto T, Yuki T, Mimura T, Miyoshi K, Tsubota N. Selective mediastinal lymphadenectomy for clinico-surgical stage I non-small cell lung cancer. Ann Thorac Surg 2006;81:1028-32. |
|5.||Khoo KL. Mediastinal re-staging of non small-cell lung cancer. Thorac Cancer 2012;3:145-9. |
|6.||Darling GE, Allen MS, Decker P, et al. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in patients with N 0 or N 1 (less than hilar) non-small cell carcinoma: Results of the ACOSOG Z0030 Trial. Am Assoc Thorac Surg 2011;139(5):1124-9. |
|7.||Lardinois D, De Leyn P, Van Schil P, Porta RR, Waller D, Passlick B, et al. ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer. Eur J Cardiothorac Surg 2006;30:787-92. |
|8.||Watanabe S, Oda M, Tsunezuka Y, Go T, Ohta Y, Watanabe G. Peripheral small-sized (2 cm or less) non-small cell lung cancer with mediastinal lymph node metastasis; clinicopathologic features and patterns of nodal spread. Eur J Cardiothorac Surg 2002;22:995-9. |
|9.||Watanabe S, Oda M, Go T, Tsunezuka Y, Ohta Y, Watanabe Y, et al. Should mediastinal nodal dissection be routinely undertaken in patients with peripheral small-sized (2 cm or less) lung cancer? Retrospective analysis of 225 patients. Eur J Cardiothorac Surg 2001;20:1007-11. |
|10.||Szczesny T, Slotwinski R, Kowalewski J, Dancewicz M, Stankiewicz A, Szczygiel B. Mediastinal lymphadenectomy influences postoperative immune response after lung cancer surgery. Zhongguo Fei Ai Za Zhi 2008;11:663-7. |
|11.||Takizawa H, Kondo K, Matsuoka H, Uyama K, Toba H, Kenzaki K, et al. Effect of mediastinal lymph nodes sampling in patients with clinical stage I non-small cell lung cancer. J Med Invest 2008;55:37-43. |
|12.||Zhou Q, Suzuki K, Anami Y, Oh S, Takamochi K. Clinicopathologic features in resected subcentimeter lung cancer - Status of lymph node metastases. Interact Cardiovasc Thorac Surg 2010;10:53-7. |
|13.||Nakamura H, Saji H, Ogata A, Saijo T, Okada S, Kato H. Lung cancer patients showing pure ground-glass opacity on computed tomography are good candidates for wedge resection. Lung Cancer 2004;44:61-8. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]