- Author: R James Koness, MD, FACS; Chief Editor: Erik D Schraga, MD more...
Cahan first described radical mediastinal lymphadenectomy in 1951. To this day, complete mediastinal lymph node dissection for non-small cell lung cancer (NSCLC) remains a controversial procedure. The procedure provides optimal staging for resectable NSCLC, but its therapeutic value remains a subject of debate. One study reported that only 57.3% of patients had any mediastinal nodes removed at the time of pulmonary resection.
Accurate pretreatment staging of mediastinal lymph nodes in lung cancer is essential to determining prognosis and treatment because patients with involved mediastinal lymph nodes may not benefit from upfront surgical resection. Computed tomography (CT) and positron emission tomography (PET) scanning lack both sensitivity and specificity for accurate lymph node staging. Transbronchial and esophageal needle aspiration provide specificity, but technical constraints hamper sensitivity.
Surgical mediastinoscopy is the pretherapeutic staging maneuver with the highest sensitivity and specificity, but it is dependent on the number of lymph nodes sampled and has technical limitations, especially for left upper lobe tumors. Additionally, the lymphatic system of the lungs has substantial anatomic variability and skip metastasis can be found in 25% of cases. Thus, a significant number of patients who undergo surgical resection of their lung cancer may harbor positive mediastinal lymph nodes.
A mediastinal lymphadenectomy may be performed to achieve complete staging (possibly to make postoperative treatment decisions), better locoregional control, and improved overall survival. Arguments against the procedure include increased operative time, possible increased morbidity, and lack of conclusive evidence to support an increased survival from the procedure.
In recent years, there has been widespread adoption of video-assisted thoracic surgery (VATS) in the surgical treatment of early-stage lung cancer. The difficulty in performing a mediastinal lymphadenectomy thoracoscopically may affect the continued use of this procedure. The writings of Dr. Robert Ginsberg in 1997 remain true today: “The addition of mediastinal lymph node dissection produces the best possible surgical and pathologic staging of lymph node disease but has yet to be proven more efficacious as a curative procedure.”
Mediastinal lymphadenectomy is indicated for T1-3 N0-1 resectable non-small cell lung cancer. Patients should be without evidence of mediastinal lymph node involvement as assessed by preoperative imaging (CT scan and/or PET scan) and sampling by mediastinoscopy, Chamberlain procedure, endoscopic ultrasound, or a transbronchial technique.
A critical review of published literature on mediastinal lymphadenectomy requires an understanding of the described operative technique. Sampling refers to the technique of removing easily found and obviously abnormal mediastinal lymph nodes. Systematic sampling refers to the routine biopsy of lymph nodes at levels or stations as specified by the authors. Complete mediastinal lymph node dissection refers to the routine complete removal of all mediastinal tissue as described by the authors.
The classification of regional lymph node stations for lung cancer staging reported by Mountain and Dresler in 1997 describes the anatomical landmarks for 14 levels of intrapulmonary, hilar, and mediastinal lymph nodes stations. TNM classification for lung cancer classifies lymph node stations into 6 zones, as follows:
Peripheral (levels 12-14) or hilar (levels 10-11) for N1 nodes
N3 lymph nodes are contralateral mediastinal, ipsilateral scalene, or supraclavicular. Among the primary tumors that had only a single involved N2 station, the most common site of lymph node metastases was level 4R for right upper-lobe tumors, levels 5/6 for left upper-lobe tumors, and level 7 for middle and lower-lobe tumors.
There are four published randomized trials comparing mediastinal lymph node dissection and mediastinal lymph node sampling.[7, 8, 9, 10] A meta-analysis of the first three trials reported a survival advantage for stages I, II, and IIIA, and a fixed-effects model by the same group reported that mediastinal lymph node dissection reduced the risk of death.[11, 12]
In the multicenter, prospective, randomized American College of Surgery Oncology Group Z0030 Trial, median survival was 8.1 years for mediastinal lymph node sampling and 8.5 years for mediastinal lymph node dissections. The authors concluded that mediastinal lymph node dissection does not improve survival in patients with early-stage NSCLC, but results are not generalizable to patients staged radiographically or those with higher stage tumors. Formal en bloc mediastinal resection may still affect survival and certainly optimally stages patients who do not undergo rigorous preoperative (mediastinoscopy) and intraoperative (mediastinal lymph node sampling) procedures.
Mediastinal lymphadenectomy is performed under general anesthesia using a double-lumen endobronchial tube followed by confirmation of correct positioning with a fiberoptic bronchoscope. The lung on the operative side is deflated during resection and mediastinal lymph node dissection to aid in visualization.
Standard lateral positioning is employed for a posterolateral, anterior axillary, or limited thoracotomy. The incision is located for a pleural entry through the fourth intercostal space. In patients with cancer in the right lung, it is possible to perform a dissection of potentially involved left contralateral tracheobronchial lymph nodes combined with a complete dissection of the right ipsilateral mediastinal lymph nodes. In patients with left lung cancer, however, contralateral right mediastinal lymph nodes cannot be adequately sampled because of anatomic constraints caused by the aortic arch.
Complete mediastinal lymph node dissection techniques have been described by Naruke and Martini. They should be performed in a standardized manner and are not dependent on the lobar location of the primary tumor.
The basic oncologic principles of lung cancer surgery determine that en bloc dissection of the mediastinum and hilum should be carried out with resection of the lobe or lung, without interrupting lymphatic channels. The order of the operative procedure should be based on operative findings and changed as necessary, ensuring that an en bloc resection is completed.
Right Upper Lobe
When a right upper lobectomy is planned, the operator starts in front of the patient. The hilar pleura is opened, the phrenic nerve is identified and retracted to prevent injury, and the superior pulmonary vein is isolated, ligated, and divided. The lung is then retracted anteriorly; the pleura is incised posterior to the hilar structures. The vagus nerve is exposed and retracted, while pulmonary branches are divided.
Next, the bifurcation of the trachea is retracted anteriorly to allow visualization of lymph node stations 10R, 7, and 10L. The mediastinal tissue between the inferior pulmonary vein, the two main stem bronchi and the carina, the pericardium, and the esophagus is dissected en bloc. At this point, the inferior pulmonary ligament is divided and lymph node stations 9 and 8 are dissected between the esophagus and pericardium from the diaphragm to the inferior pulmonary vein.
The surgeon then moves to the back of the patient to complete the superior mediastinal dissection. If not previously divided, the azygos vein is now transfixed and divided. When station 4 nodes are grossly involved, the vein should be divided proximally as it enters the superior vena cava. The distal portion of the azygos over the transbronchial lymph nodes (station 4) is left attached to this nodal group and excised en bloc.
The dissection is then completed by removing the right paratracheal, pretracheal, and tracheobronchial nodes (stations 2, 3, and 4) lateral and anterior to the trachea, the ascending aorta, and posterior aspect of the superior vena cava, from the brachiocephalic artery to the right pulmonary artery.
The lobectomy is completed by ligation and division of the right pulmonary artery and removal of lymph nodes attached to the anterior aspect of the upper lobe bronchus (station 12) in continuity with the tracheobronchial lymph nodes (station 4). The procedure is completed with isolation, division, and closure of the right upper lobe bronchus.
Right Middle Lobe
For patients with cancer in the right middle lobe, a bilobectomy (with either the upper or lower lobe) and mediastinal lymph node dissection is performed as for a right upper lobectomy.
Right Lower Lobe
For tumors of the right lower lobe, the operative surgeon begins by standing at the back of the patient. The mediastinal pleura is opened anterior and posterior to the inferior pulmonary ligament. The esophagus is exposed from the diaphragm to the inferior pulmonary vein.
Dissection is carried out in a superior direction. The pulmonary ligament and paraesophageal (stations 9 and 8) are dissected en bloc with adjacent fatty tissue up to the inferior pulmonary vein, which is then ligated and divided.
The surgeon then moves to the front of the patient where the esophagus is retracted posteriorly and the lung anteriorly. Dissection continues there with the lymph nodes at the bifurcation of the trachea, followed by lymph nodes along the right main-stem bronchus (stations 7 and 10).
Next, the major interlobar fissure is opened to expose the bronchovascular structures, where the inferior pulmonary artery and lower lobe bronchus are exposed, ligated, and divided. Dissection of the superior mediastinal lymph nodes should then be carried out as previously described.
Keep in mind that nodal metastases to the lower mediastinum from upper lobe cancer have more frequently been observed than the lower lobe cancer to the upper mediastinum.
Left Upper Lobe
For a left upper lobectomy, the surgeon stands to the front of the patient after performing a thoracotomy into the pleural space through the fourth or fifth intercostal space. The mediastinal pleura is opened anterior to the hilum, where the phrenic nerve is identified and preserved and the superior pulmonary vein is isolated, ligated, and divided.
The lung is retracted anteriorly and the descending aorta and esophagus are retracted posteriorly. The lymph node tissue is dissected away from the inferior surface of the right main stem bronchus (station 10) and the subcarinal lymph nodes (stations 7) are dissected free.
Next, the upper mediastinal pleura is incised to the apex of the thorax. The hemiazygos vein is identified, ligated, and divided and the ascending aorta is exposed. Working posteriorly, paraaortic as well as subaortic lymph nodes (stations 6 and 5) can be dissected out. Inferior paraesophageal and pulmonary ligament lymph nodes (stations 8 and 9) can be removed at this point.
Next, the left common carotid and the left subclavian arteries are exposed at the apex of the thorax, and caudal dissection of fatty tissue containing the lymph nodes is carried out. The right paratracheal, pretracheal, and tracheobronchial nodes (stations 2, 3, and 4) are removed en bloc between the lateral and anterior border of the trachea, the ascending aorta, and the posterior aspect of the superior vena cava, and from the brachiocephalic artery to the right pulmonary artery.
The thoracic duct is in the deepest area between the left common carotid artery and the left subclavian artery. It is not usually identified; thus all lymphatic channels and fine blood vessels should be ligated before division. Furthermore, in left thoracotomies, the ligamentum botalli must be ligated, divided, and the aorta mobilized to dissect the lymph node station 4.
Left Lower Lobe
When a left lower lobectomy is performed in patients with left lower lobe cancer, the surgeon stands to the front of the patient. The inferior pulmonary ligament is released; the pulmonary and paraesophageal lymph nodes (stations 9 and 8) are procured.
Moving superiorly, the inferior pulmonary vein is identified, ligated, and divided. The lung and trachea are moved anteriorly and subcarinal and hilar lymph nodes (stations 7 and 10) are dissected away. The mediastinal lymph node dissection is completed by removing lymph nodes from the subaortic and paraaortic regions (stations 5 and 6). The oblique fissure is opened and the interlobar nodes (station 11) are included with the removal of the lower lobe.
The lower lobectomy is completed with ligation and division of the inferior pulmonary artery and division and closure of the bronchus. Usually, no formal node dissection above the aortic arch is carried out, except when enlarged or palpable nodes are noted on exploration. Division of the ligamentum arteriosum is not necessary.
Complete resection of the lung includes resecting all lobar and interlobar lymph nodes. After resection of the lung or lobe and mediastinal lymph nodes, the specimen should be examined. The lymph node stations are labeled and oriented for full pathologic review.
Mediastinal lymph node dissection can be done en bloc with the lobe or lung to be removed, but this is not absolutely necessary. Regardless, labeling and communication with pathology is essential to accurate staging.
Either systematic lymph node sampling or complete mediastinal lymph node dissection may be associated with complications related to the possible interruption of blood supply to the bronchial stump, removal of a large amount of intrathoracic lymphatics, and possible nerve injury.
However, MLND itself is not associated with any loss of pulmonary function. Izbicki reported the most complete data on morbidity in the first publication from the German group. This randomized trial compared MLNS to MLND in 182 patients. The complete lymph node dissection required 22 minutes longer to perform but was associated with no increase in mortality, intraoperative blood loss, or need for repeat thoracotomy.
Postoperatively, no difference was noted in the number of patients with complications or any specific complication except a nonsignificant trend in chest tube air leaks (>5 days) and number of patients receiving more than 2 units in the 30-day postoperative time period. Length of intensive care unit and hospital stay was not dissimilar. In summary, MLND has no impact on operative morbidity, mortality, and quality of life, and such concerns should have no impact on the decision to include this procedure in the surgical lung resection.
Combined Videothoracoscopic and Videomediastinaoscopic Approach
Video-assisted thoracoscopic (VATS) lobectomy, introduced in the early 1990s, has become a popular and accepted alternative to open thoracotomy techniques.[16, 17] Reported benefits include faster patient recovery with less pain, fewer respiratory complications, and shorter hospital stay without compromising the oncologic complete resection.
Presently, VATS has been used by a number of thoracic surgeons with expertise in mediastinal staging. Although thoracoscopic techniques allow access to most of the nodal stations accessible to mediastinoscopy, it also allows access to nodal stations not accessible, such as subaortic, para-aortic, paraesophageal, and inferior pulmonary ligament nodes (stations 5, 6, 8, and 9).
Although useful in right-sided neoplasms, VATS plays an even more valuable role in left-sided cancers. Aortopulmonary window (station 5) and paraaortic (station 6) lymph nodes are inaccessible by standard cervical mediastinoscopy. VATS has replaced anterior mediastinotomy (Chamberlain procedure) as the procedure of choice, allowing for superior visualization, less surgical time, and providing more information about the extent of local disease.
VATS is at best an advanced staging procedure; it is not presently a method capable of complete mediastinal or hilar lymph node dissection. In 2002, Hurtgen published his initial experience on video-assisted mediastinoscopic lymphadenectomy (VAMLA). They used a 2-bladed spreading cervical laryngoscope developed by Linder and Dahan in cooperation with the Wolf Company (Richard Wolf GmbH, Knittlingen, Germany; see image below).
This instrument markedly increases surgical options, allowing for bimanual dissection of lymph node tissue and limiting mediastinal structures that are much better exposed than in standard mediastinoscopy. In 46 VAMLA procedures, the mean number of nodes removed was 20.7, with one left-sided recurrent nerve palsy.
One year later, Leschber and Linder reported on 25 procedures in which the mean number of resected lymph nodes as determined by the surgeon was 8.6. More importantly, 18 patients subsequently underwent thoracotomy for resection and standard lymphadenectomy. No false-negative lymph nodes were discovered, and they concluded that VAMLA could be used together with VATS to achieve a complete mediastinal lymph node dissection. European and Asian groups have reported results of this combined approach.
Witte prospectively collected their VATS resections for cancer and compared those that underwent VATS alone (14 patients) to those who were had a VATS plus VAMLA (18 patients). Both the mean number of dissected mediastinal lymph nodes stations (6.4 vs 3.6) and the mediastinal sample weight (11.2 vs 5.5 g) were significantly higher in the VATS plus VAMLA group. The improved radicality was realized without increased total operative time, morbidity, or drainage time. VAMLA was performed before or after VATS in a combined procedure or sometimes staged within 1 week prior to avoid mediastinal fibrosis.
Yoo published their results with 108 consecutive VAMLA lung cancer patients, 103 of which also had a lung resection (101 were performed with VATS). During combined or staged operations, no residual lymph nodes were found in stations 2R, 4R, and 7 in right-sided lung cancer, and in stations 4L and 7 in left-sided lung cancer. In their experience, a mean number of 16 mediastinal nodes and a mean number of 3.5 stations were removed, with no known false negative lymph nodes noted at resection. The mean operative time for VAMLA was 39.8 minutes, and 5 complications were observed: all were recurrent laryngeal nerve palsies. To avoid this complication, they recommend visual identification of the left recurrent nerve, systematic sampling instead of en bloc resection of stations 2L and 4L, and the use of clips for hemostasis instead of electrocautery.
Lung cancer is the leading cause of cancer death in the United States. Mediastinal assessment is essential for accurate staging of disease; however, patterns of care suggest that mediastinal nodes are not always removed at the time of pulmonary resection. CT scans, PET-CT scans, and endoscopic methods are not equivalent to invasive staging procedures. The extent of mediastinal lymph node removal and its effect on survival have long been controversial. The recently published results of the long-awaited ACOS Z0030 study suggests that complete mediastinal lymphadenectomy does not improve survival for early-stage NSCLC. However, remember that in this randomized trial, complete dissection was compared to rigorous systematic sampling. Thus, surgeons adhering to the highest standards of complete lung cancer staging should continue to perform thorough mediastinal lymph node sampling.
Complete mediastinal lymphadenectomy will continue to be performed in medical centers demanding the most comprehensive information. This is justified by previous data demonstrating that the dissection can be performed with minimal time and no increase in morbidity and mortality. For centers pursuing minimally invasive techniques, VATS mediastinal lymph node staging and VAMLA are clinically feasible procedures with accurately staging and acceptable complication rate. Academic medical centers with the infrastructure and experience will provide the data needed validate the application of noninvasive techniques to optimally stage and ultimately treat patients with NSCLC.
Cahan WG, Watson WL, Pool JL. Radical pneumonectomy. J Thorac Surg. 1951 Nov. 22(5):449-73. [Medline].
Little AG, Rusch VW, Bonner JA, Gaspar LE, Green MR, Webb WR. Patterns of surgical care of lung cancer patients. Ann Thorac Surg. 2005 Dec. 80(6):2051-6; discussion 2056. [Medline].
Hata E, Haykawa K, Miyamoto H, et al. Rationale for extended lymphadenectomy for lung cancer. Theor Surg. 1990. 5:19-25.
Ginsberg RJ. Resection of non-small cell lung cancer: how much and by what route. Chest. 1997 Oct. 112(4 Suppl):203S-205S. [Medline].
Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest. 1997 Jun. 111(6):1718-23. [Medline].
Rusch VM, Crowley J, Giroux DJ, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2007. 2:603-12.
Izbicki JR, Passlick B, Pantel K, Pichlmeier U, Hosch SB, Karg O. Effectiveness of radical systematic mediastinal lymphadenectomy in patients with resectable non-small cell lung cancer: results of a prospective randomized trial. Ann Surg. 1998 Jan. 227(1):138-44. [Medline].
Sugi K, Nawata K, Fujita N, Ueda K, Tanaka T, Matsuoka T. Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter. World J Surg. 1998 Mar. 22(3):290-4; discussion 294-5. [Medline].
Wu Y, Huang ZF, Wang SY, Yang XN, Ou W. A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer. 2002 Apr. 36(1):1-6. [Medline].
Darling GE, Allen MS, Decker PA, Ballman K, Malthaner RA, Inculet RI. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial. J Thorac Cardiovasc Surg. 2011 Mar. 141(3):662-70. [Medline].
Wright G, Manser RL, Byrnes G, Hart D, Campbell DA. Surgery for non-small cell lung cancer: systematic review and meta-analysis of randomised controlled trials. Thorax. 2006 Jul. 61(7):597-603. [Medline].
Manser R, Wright G, Hart D, et al. Surgery for early stage non-small cell lung cancer (Cochrane Review),. The Cochrane Library, Issue 1. Chichester, UK: John Wiley & Sons; 2005.
Naruke T. Mediastinal Lymph Node Dissection. In General Thoracic Surgery. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2005.
Martini N. Mediastinal lymph node dissection for lung cancer. The Memorial experience. Chest Surg Clin N Am. 1995 May. 5(2):189-203. [Medline].
Watanabe Y, Shimizu J, Tsubota M, Iwa T. Mediastinal spread of metastatic lymph nodes in bronchogenic carcinoma. Mediastinal nodal metastases in lung cancer. Chest. 1990 May. 97(5):1059-65. [Medline].
Whitson BA, Groth SS, Duval SJ, Swanson SJ, Maddaus MA. Surgery for early-stage non-small cell lung cancer: a systematic review of the video-assisted thoracoscopic surgery versus thoracotomy approaches to lobectomy. Ann Thorac Surg. 2008 Dec. 86(6):2008-16; discussion 2016-8. [Medline].
Yan TD, Black D, Bannon PG, McCaughan BC. Systematic review and meta-analysis of randomized and nonrandomized trials on safety and efficacy of video-assisted thoracic surgery lobectomy for early-stage non-small-cell lung cancer. J Clin Oncol. 2009 May 20. 27(15):2553-62. [Medline].
Cerfolio RJ, Bryant AS, Eloubeidi MA. Accessing the aortopulmonary window (#5) and the paraaortic (#6) lymph nodes in patients with non-small cell lung cancer. Ann Thorac Surg. 2007 Sep. 84(3):940-5. [Medline].
Hürtgen M, Friedel G, Toomes H, Fritz P. Radical video-assisted mediastinoscopic lymphadenectomy (VAMLA)--technique and first results. Eur J Cardiothorac Surg. 2002 Feb. 21(2):348-51. [Medline].
Leschber G, Holinka G, Linder A. Video-assisted mediastinoscopic lymphadenectomy (VAMLA)--a method for systematic mediastinal lymphnode dissection. Eur J Cardiothorac Surg. 2003 Aug. 24(2):192-5. [Medline].
Witte B, Messerschmidt A, Hillebrand H, Gross S, Wolf M, Kriegel E. Combined videothoracoscopic and videomediastinoscopic approach improves radicality of minimally invasive mediastinal lymphadenectomy for early stage lung carcinoma. Eur J Cardiothorac Surg. 2009 Feb. 35(2):343-7. [Medline].
Yoo DG, Kim YH, Kim DK, Kim HR, Park SI. Clinical feasibility and surgical benefits of video-assisted mediastinoscopic lymphadenectomy in the treatment of resectable lung cancer. Eur J Cardiothorac Surg. 2011 Dec. 40(6):1483-6. [Medline].