Mediastinal Lymphadenectomy 

Updated: Dec 10, 2019
Author: R James Koness, MD, FACS; Chief Editor: Erik D Schraga, MD 

Overview

Background

After Cahan's first description of radical mediastinal lymphadenectomy in 1951,[1]  complete mediastinal lymph node dissection for non-small cell lung cancer (NSCLC) remained a controversial procedure. The procedure was found to provide optimal staging for resectable NSCLC, but its therapeutic value continued to be debated. One study reported that only 57.3% of patients had any mediastinal nodes removed at the time of pulmonary resection.[2]

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) 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.[3]  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 operating time, possible increased morbidity, and lack of conclusive evidence to support an increased survival rate from the procedure.

The results of the American College of Surgeons Oncology Group (ACOSOG) Z0030 study suggested that complete mediastinal lymphadenectomy does not improve survival for early-stage NSCLC. However, in this trial, complete dissection was compared with rigorous systematic sampling. Thus, surgeons adhering to the highest standards of complete lung cancer staging should continue to perform thorough mediastinal lymph node sampling.

There is growing acceptance of video-assisted thoracoscopic 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 statement made by Robert Ginsberg in 1997 remains 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.”[4]

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 video-assisted mediastinal lymphadenectomy (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.

Transcervical extended mediastinal lymphadenectomy (TEMLA) is another approach that has been the subject of increasing interest.[5, 6]

Indications

Mediastinal lymphadenectomy is indicated for T1-3 N0-1 resectable NSCLC. Patients should be without evidence of mediastinal lymph node involvement as assessed by preoperative imaging (CT, PET, or both) and sampling by means of mediastinoscopy, a Chamberlain procedure, endoscopic ultrasonography (US), or a transbronchial technique.

Technical Considerations

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 anatomic landmarks for 14 levels of intrapulmonary, hilar, and mediastinal lymph nodes stations.[7] TNM classification for lung cancer classifies lymph node stations into six zones, as follows:

  • Peripheral (levels 12-14) or hilar (levels 10-11) for N1 nodes
  • Upper (levels 1-4) or lower mediastinal (levels 8-9), aortopulmonary (levels 5-6), and subcarinal (level 7) for N2 nodes (see the image below)
Regional lymph node stations. Regional lymph node stations.

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.[8]

Outcomes

Four published randomized trials compared mediastinal lymph node dissection and mediastinal lymph node sampling.[9, 10, 11, 12]  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.[13, 14]

In the multicenter, prospective, randomized ACOSOG Z0030 Trial,[12]  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.

Call et al assessed the results of VAMLA for staging NSCLC in 160 cases, 138 of which involved clinical N0-1 cancers.[15]  They found VAMLA to be highly accurate, with a sensitivity of 0.96 (95% confidence interval [CI], 0.81-99.3), a specificity of 1 (95% CI, 0.97-1), a positive predictive value of 1 (95% CI, 0.87-1), a negative predictive value of 0.99 (95% CI, 0.95-0.99), and a diagnostic accuracy of 0.99 (95% CI, 0.96-0.99). Complications developed in 5.9% of patients.

Wang et al retrospectively studied 712 consecutive cases of clinical N0-1 lung cancer (including 152 cases of pathologic N2 disease and 560 cases of pathologic N0-1 disease confirmed after surgery) to assess whether mediastinal lymphadenectomy compliant with National Comprehensive Cancer Network (NCCN) criteria (≥3 stations of N2 node dissection) improved oncologic outcomes in this group.[16] They found that such a lymphadenectomy was a significant prognostic factor for overall survival both in the cohort as a whole and the patients with pathologic N2 status; more extended N2 node dissection did not appear to improve outcome further in the latter.

 

Periprocedural Care

Patient Preparation

Anesthesia

Mediastinal lymphadenectomy is performed with general anesthesia using a double-lumen endobronchial tube followed by confirmation of correct positioning with a fiberoptic bronchoscope. To facilitate visualization, the lung on the operative side is deflated during resection and mediastinal lymph node dissection.

Positioning

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 right-lung cancer, 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 imposed by the aortic arch.

 

Technique

Approach Considerations

Complete mediastinal lymph node dissection techniques have been described by Naruke[17]  and Martini.[18]  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 interruption of lymphatic channels. The order of the operative procedure should be based on operative findings and changed as necessary to ensure that an en-bloc resection is completed.

Mediastinal Lymph Node Dissection

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 mainstem 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 (SVC). 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 the posterior aspect of the SVC, 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 operating 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 mainstem bronchus (stations 7 and 10).

Next, the major interlobar fissure is opened to expose the bronchovascular structures, where the inferior pulmonary artery and the 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 metastasizing to the upper mediastinum.[19]

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 mainstem 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. By working posteriorly, para-aortic 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 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 SVC, 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 arteriosum (ligament of Botallo) must be ligated and divided and the aorta mobilized to dissect 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.

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 para-aortic 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.

Node resection

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 ensure accurate staging.

Combined Videothoracoscopic and Videomediastinoscopic Approach

Lobectomy by means of video-assisted thoracoscopic surgery (VATS), introduced in the early 1990s, has become a popular and accepted alternative to open thoracotomy techniques.[20, 21, 22]  Reported benefits include faster patient recovery with less pain, fewer respiratory complications, and shorter hospital stay without compromising the oncologic complete resection.

VATS has been used by a number of thoracic surgeons with expertise in mediastinal staging. Although thoracoscopy allows 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-side neoplasms, VATS plays an even more valuable role in left-side cancers. Aortopulmonary window (station 5) and para-aortic (station 6) lymph nodes are inaccessible via standard cervical mediastinoscopy. VATS has replaced anterior mediastinotomy (the Chamberlain procedure) as the procedure of choice, allowing superior visualization, requiring less operating time, and providing more information about the extent of local disease.[23]

In 2002, Hurtgen et al published their initial experience with video-assisted mediastinoscopic lymphadenectomy (VAMLA).[24]  They used a two-bladed spreading cervical laryngoscope developed by Linder and Dahan in cooperation with the Wolf Company (Richard Wolf GmbH, Knittlingen, Germany; see the image below).

Video-mediastinoscope (Wolf Company, Knittlingen, Video-mediastinoscope (Wolf Company, Knittlingen, Germany), with the 2 blades opened for demonstration.

This instrument markedly increases surgical options, allowing 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 recurrent nerve palsy on the left side.[24]

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.[25]  More important, 18 patients subsequently underwent thoracotomy for resection and standard lymphadenectomy. No false-negative lymph nodes were discovered, and the authors concluded that VAMLA could be used together with VATS to achieve a complete mediastinal lymph node dissection. European and Asian groups subsequently reported results of this combined approach.

Witte et al prospectively collected their VATS resections for cancer and compared patients who underwent VATS alone (n = 14) with those who underwent VATS plus VAMLA (n = 18).[26]  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 operating 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 et al published their results with 108 consecutive VAMLA lung cancer patients, 103 of whom also had a lung resection (101 were performed with VATS).[27]  During combined or staged operations, no residual lymph nodes were found in stations 2R, 4R, and 7 in right-side lung cancer or in stations 4L and 7 in left-side lung cancer. A mean of 16 mediastinal nodes and a mean of 3.5 stations were removed, with no known false-negative lymph nodes noted at resection.

The mean operating time for VAMLA in this study was 39.8 minutes, and five complications were observed, all of them recurrent laryngeal nerve palsies.[27] To avoid this complication, Yoo et al recommended 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.

Zhang et al retrospectively studied the surgical outcomes of 497 non-small cell lung cancer (NSCLC) patients who underwent mediastinal lymph node dissection VATS (n = 242) or thoracotomy (n = 255).[28] The range of dissection included groups 2R, 4R, 7, 8, 9 in right-side cancer procedures and groups 4L, 5, 6, 7, 8, 9 in left-side procedures. VATS was associated with quicker recovery, fewer postoperative complications, and shorter hospital stays, with comparable surgical outcomes. Thoracotomy, however, had an advantage with regard to dissection of group 7L nodes.

Complications

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, mediastinal lymph node dissection 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.[9]  This randomized trial compared mediastinal lymph node sampling with mediastinal lymph node dissection 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.[9] Length of intensive care unit (ICU) and hospital stay was not dissimilar. In summary, mediastinal lymph node dissection 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.

 

Questions & Answers