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Surgical Mediastinal Lymph Node Sampling for Staging of Non-Small Cell Lung Carcinoma

      Mediastinal lymph node sampling has been used to diagnose lymphoma and sarcoidosis and to diagnose and stage non-small-cell lung cancer (NSCLC). The optimal treatment of patients with NSCLC is determined by mediastinal lymph node involvement. Surgical staging is the gold standard for NSCLC patient management.
      It is mandatory to sample lymph nodes that are greater than 1 cm on computed tomographic scan
      • Passlick B.
      Initial surgical staging of lung cancer.
      and fluorodeoxyglucose-positive lymph nodes on positron emission tomography.
      • Gonzalez-Stawinski G.V.
      • Lemaire A.
      • Merchant F.
      • et al.
      A comparative analysis of positron emission tomography and mediastinoscopy in staging non-small cell lung cancer.
      Daniels, using an empiric scalene lymph node biopsy, first described lymph node sampling to assess resectability of lung cancer in 1949.
      • Daniels A.C.
      A method of biopsy useful in diagnosing certain intrathoracic disease.
      The first mediastinal lymph node sampling was done in 1954 by Harken using a laryngoscope through a supraclavicular incision. Carlens modified this in 1959 to a pretracheal incision for insertion of a mediastinoscope.
      • Carlens E.
      Mediastinoscopy: A method for inspection and tissue biopsy in the superior mediastinum.
      Cervical mediastinoscopy was championed in North America in the 1960s by Pearson and colleagues at the Toronto General Hospital.
      • Pearson F.G.
      Mediastinoscopy: A method of biopsy in the superior mediastinum.

      Cervical Mediastinoscopy

      Cervical mediastinoscopy allows for sampling of ipsilateral and contralateral lymph nodes at stations 2, 4, and 7 and it is highly sensitive and specific.
      • Porte H.
      • Roumilhac D.
      • Eraldi L.
      • et al.
      The role of mediastinoscopy in the diagnosis of mediastinal lymphadenopathy.
      Computed tomography and positron emission tomographic scans have been used to clinically assess for mediastinal lymph node involvement. However, these imaging modalities both share a low positive-predictive value; all suspicious nodes on imaging need to be assessed surgically.
      • Gonzalez-Stawinski G.V.
      • Lemaire A.
      • Merchant F.
      • et al.
      A comparative analysis of positron emission tomography and mediastinoscopy in staging non-small cell lung cancer.
      Other minimally invasive methods of sampling, such as endobronchial ultrasound-guided transbronchial fine-needle aspiration, do have specific advantages when compared with cervical mediastinoscopy but have not yet proven to be as efficacious as a routine staging tool.
      Cervical mediastinoscopy has very low morbidity and mortality and is today considered to be an outpatient procedure.
      • Cybulsky I.J.
      • Bennett W.F.
      Mediastinoscopy as a routine outpatient procedure.
      Morbidity rates of 0.6% to 3.7% and mortality rates of 0% to 0.3% have been reported.
      • Park B.J.
      • Flores R.
      • Downey R.J.
      • et al.
      Management of major hemorrhage during mediastinoscopy.
      Complications include bleeding, recurrent laryngeal nerve injury, and tracheobronchial injury. Contraindications are inability to tolerate general anesthesia, extreme kyphosis, previous mediastinoscopy, and cutaneous tracheostomy. A heavily calcified aorta is also a relative contraindication due to concern for athero-embolism from external manipulation. Bleeding can be controlled in most cases by local tamponade with a 4 × 8 gauze sponge or vaginal gauze packing placed through the scope using the scope to achieve direct compression. This critical maneuver allows better identification and visualization of the specific injury and can prevent catastrophic hemorrhage. If packing and direct pressure do not result in hemostasis after 10 to 15 minutes, then an open approach to address the source of bleeding will be required. Repacking allows the anesthesia team time to obtain better vascular access, to obtain blood products in the room, and to achieve selective lung ventilation if needed. Level 4R has been shown to be the most common site of bleeding.
      • Park B.J.
      • Flores R.
      • Downey R.J.
      • et al.
      Management of major hemorrhage during mediastinoscopy.
      To perform a cervical mediastinoscopy, the patient is positioned supine with extension of the neck using a shoulder role to elevate both scapulae. The patient should be prepped for a sternotomy in the rare instance that uncontrollable bleeding is encountered. A 3-cm transverse incision is made 1 cm above the suprasternal notch (Fig. 1A and B). The platysma muscle is divided transversely and the strap muscles are split in the midline. Army-Navy retractors are used to reflect the strap muscles laterally and to retract the inferior poles of the thyroid gland in a cephalad direction, exposing the pretracheal fascia (Fig. 2) Scissors are used to gain access to this space. Digital dissection is used to develop an operative plane along the left and right paratracheal spaces and anteriorly in the subinnominate space (Fig. 3A and B). In the right paratracheal space, one can identify the innominate artery, stations 2R and 4R nodes, as well as the azygous vein (Figs. 4 and Fig 5A and B). On the left side, stations 2L and 4L nodes are seen and the left recurrent laryngeal nerve can be visualized, although vigorous dissection to identify it is unnecessary and could be potentially harmful (Figs. 6 and Fig 7). Cautery should be avoided in this area due to the risk of injury to the left recurrent laryngeal nerve.
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      Figure 1(A) Anterior view of the patient positioned in the supine position. The patient should be prepped for a full sternotomy in case uncontrollable bleeding is encountered. A 3-cm incision is made one finger-breath above the sternal notch. (B) Lateral view of positioned patient. A roll is place between the scapulae and the neck is in extension.
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      Figure 2The platysma is divided and the strap muscles are split. The inferior portion of the thyroid is retracted cranially exposing the pretracheal fascia. m. = muscle.
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      Figure 3(A) Digital dissection is used to expose the left and right paratracheal and subinnominate spaces. (B) Anterior view showing the mediastinal lymph nodes and their relation to the tracheobronchial tree and major vessels. a. = artery; Ao = aorta; PA = pulmonary artery; pulm. lig. = pulmonary ligament; SVC = superior vena cava; v. = vein.
      Figure thumbnail gr4
      Figure 4Right paratracheal space showing the innominate artery, azygous vein, and station 4R. a. = artery; Az = azygous vein; SVC = superior vena cava.
      Figure thumbnail gr5
      Figure 5Video-mediastinoscopy images of (A) right paratracheal dissection, (B) an enlarged station 4R lymph node, (C) needle-aspiration of the 4R node, and (D) cold-cupped biopsy of the 4R node.
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      Figure 6Lateral view of the trachea showing the left recurrent laryngeal nerve in the groove between the trachea and esophagus. n. = nerve.
      Figure thumbnail gr7
      Figure 7Left paratracheal space showing stations 2L and 4L and the recurrent laryngeal nerve. The subcarinal space containing station 7 and its proximity to the right pulmonary artery is also shown. n. = nerve.
      The subcarinal space contains station 7 lymph nodes (Fig. 7). Lymph node sampling is undertaken under direct visualization with cold-cupped biopsy forceps. When there is concern whether the identified “node” could actually be a vessel, we aspirate the target with a 21-G spinal needle before introducing the biopsy forceps (Fig. 5C and D).
      Video-assisted mediastinoscopy has become increasingly popular. Instead of using a conventional mediastinoscope, a Linder-Dahan videomediastinoscope consisting of a twin-bladed speculum is used. This scope creates a wider field of vision and allows for bimanual dissection. This combined with the video-image allows for more surgical options, increased precision, improved documentation, and easier use with trainees. Reported complication rates are similar to conventional cervical mediastinoscopy.
      • Witte Bruta
      • Wolf M.
      • Huertgen M.
      • et al.
      Video-assisted mediastinoscopic surgery: Clinical feasibility and accuracy of mediastinal lymph node staging.
      One surgical technique that video-assisted mediastinoscopy has made possible is video-assisted mediastinoscopic lymphadenectomy. As opposed to lymph node sampling done by conventional cervical mediastinoscopy, the pertinent lymph node stations are completely dissected and removed. This resection of more lymphatic tissue decreases the false-negative rate and will most certainly lead to more accurate pathologic staging. Video-assisted mediastinoscopy lymphadenectomy also is helpful for patients needing a video-assisted thoracoscopic surgery (VATS) lobectomy. During VATS lobectomy especially on the left, subcarinal lymphadenectomy can be very difficult and therefore doing a complete pre-VATS lymphadenectomy is potentially advantageous.
      • Leschber G.
      • Holinka G.
      • Linder A.
      Video-assisted mediastinoscopic lymphadenectomy (VAMLA)—A method for systematic mediastinal lymph node dissection.
      The aortopulmonary window and the prevascular or para-aortic lymph nodes, stations 5 and 6, are difficult to assess with cervical mediastinoscopy. Ginsberg and colleagues have described using extended cervical mediastinoscopy to assess stations 5 and 6.
      • Ginsberg R.J.
      • Rice T.W.
      • Goldberg M.
      • et al.
      Extended cervical mediastinoscopy A single staging procedure for bronchogenic carcinoma of the left upper lobe.
      However, this is a technically demanding procedure that has not gained in popularity. Alternatively, an anterior mediastinotomy, also known as the Chamberlain procedure, has been used to access this area. As opposed to cervical mediastinoscopy, which accesses the middle mediastinum, here the anterior mediastinum is accessed. An incision is usually made at the second left intercostal space for optimal access (Fig. 8) It was originally done in an open fashion but is now done with a Carlen's mediastinoscope. A portion of the medial (cartilaginous) left second rib can be resected in the subperichondrial plane to enhance exposure.
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      Figure 8Incision is made over the left second rib.

      Anterior Mediastinoscopy

      We typically do not use a double lumen endotracheal tube for anterior mediastinotomy, preferring brief periods of apnea if the inflated lung obscures our view. We make a 5- to 6-cm incision directly anterior to the second rib in the left peristernal position; through this access, a mediastinoscope is inserted. The pleura is reflected laterally while the internal thoracic vessels are swept medially to gain access to the anterior mediastinum and the aortopulmonary (station 5) and prevascular or para-aortic (station 6) lymph nodes (Figs. 9 and Fig 10) Although we attempt to avoid entering the pleural space, this can happen especially in thin or hyperinflated/emphysematous patients. In such cases, we evacuate the passive pneumothorax with a simple red rubber catheter during a Valsalva maneuver before skin closure. An indwelling chest drain is unnecessary.
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      Figure 9Operator view looking posteriorly with the lung retracted laterally. The patient's head is beyond the bottom of the image and feet beyond the top. The aortopulmonary window is in the field. Stations 5 and 6 are shown. The internal thoracic vessels are medial. PA = pulmonary artery.
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      Figure 10Lateral view showing PA, aorta, stations 5 and 6, phrenic, vagus, and recurrent laryngeal nerves. n. = nerve; PA = pulmonary artery.

      VATS

      VATS is another highly accurate way of assessing stations 5 and 6 and has become increasingly popular, replacing anterior mediastinotomy in some centers. It allows concurrent therapeutic resection of pulmonary malignancy if the mediastinal nodes are benign. VATS exploration allows for better visualization of the lymph nodes and their relationships to the great vessels and phrenic and vagus nerves and allows inspection of the entire ipsilateral mediastinum and pleural space. The operator can biopsy pleural and pericardial lesions and visualize vascular involvement. VATS avoids internally mammary artery conduits in patients who have had a coronary artery bypass. Especially useful for patients with left upper lobe tumors, VATS can provide better visualization of the relevant N1 and N2 lymph nodes.
      • Cerfolio R.J.
      • Bryant A.S.
      • Eloubeidi M.A.
      Accessing the aortopulmonary window (#5) and the paraaortic (#6) lymph nodes in patients with non-small cell lung cancer.
      VATS is done using two to four ports utilizing 1- to 2-cm incisions (Fig. 11). The patient is placed in the lateral decubitus position and split-lung ventilation is required. A lung retractor is used with the other ports being used for the camera and the biopsy forceps (Fig. 12).
      Figure thumbnail gr11
      Figure 11Port sites and patient position for VATS. Two 5-mm ports are placed—one in the third intercostal space at the lateral edge of the pectoralis major muscle and one in the fifth intercostal space at the tip of the scapula. A 10-mm port for the camera is placed in the fifth intercostal space in the anterior axillary line.
      Figure thumbnail gr12
      Figure 12A lung retractor is placed to aid visualization. Camera and biopsy forceps are placed in the two other ports. n. = nerve.

      Conclusions

      Cervical mediastinoscopy is the gold standard for sampling mediastinal lymph nodes at stations 2, 4, and 7. It is a safe, accurate, and an ambulatory procedure. Although lymph node biopsy via endoesophageal or endobronchial ultrasound is emerging as alternative methods for evaluating worrisome adenopathy, these techniques have not proven to be superior to cervical mediastinoscopy, especially for the routine staging of lung cancer. Anterior mediastinotomy remains a useful technique to assess stations 5 and 6 in the outpatient setting. VATS requires more sophisticated anesthetic management and usually requires hospital admission. VATS has gained in popularity as it provides enhanced viewing of adjacent structures and more comprehensive sampling of the aortopulmonary window and the para-aortic or prevascular lymph nodes as well as the opportunity to proceed to therapeutic resection if mediastinal staging is histologically benign.

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