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Surgical evaluation of mediastinal lymphadenopathy

Surgical evaluation of mediastinal lymphadenopathy
Literature review current through: Jan 2024.
This topic last updated: Oct 13, 2022.

INTRODUCTION — The evaluation of mediastinal nodes is paramount for staging patients with suspected or proven bronchogenic carcinomas [1]. The National Comprehensive Cancer Network Guidelines for non-small cell lung cancer recommend that pretreatment evaluation include pathological mediastinal lymph node evaluation for patients clinically assessed to have stage IB (peripheral T2a, N0), stage I (central T1ab-T2a, N0), stage II (T1ab-T2ab, N1; T2b, N0), stage IIIA (except when unresectable) or IIIB disease, or those with separate pulmonary nodule(s) [2]. The operative procedures are the standard approach for evaluating mediastinal adenopathy and for establishing the diagnosis of a primary or secondary mediastinal malignancy (eg, lymphoma, thymoma, breast cancer).

The operative approach for evaluation of mediastinal lymphadenopathy and the complications of the procedures are discussed here. The differential diagnosis, radiographic evaluation, and pathology of mediastinal masses are reviewed separately. (See "Approach to the adult patient with a mediastinal mass" and "Pathology of mediastinal tumors".)

CLASSIFICATION OF MEDIASTINAL LYMPH NODES — Mediastinal lymph nodes are located in the anterior, middle, and posterior mediastinal compartments (figure 1 and figure 2). Most of the mediastinal nodes are in close approximation to the left innominate vein, the anterior surface of the trachea, and circumference of the main bronchi, and inferior and to the left of the aortic arch [1].

The International Association for the Study of Lung Cancer (IASLC) proposed classifying mediastinal nodes into regional lymph node stations and zones [3,4]. The lymph node stations and zones are shown in the figure (figure 3) [3].

SELECTION OF BIOPSY PROCEDURE — Selection of the biopsy procedure depends on the stations of adenopathy and a history of prior neck and mediastinal surgical procedures. The procedure options include cervical mediastinoscopy, thoracoscopy, anterior mediastinotomy, endobronchial ultrasound, navigational bronchoscopy, and esophageal ultrasound [5].

Mediastinoscopy – Mediastinoscopy can be performed as video-assisted or direct optic visualization and is used to biopsy upper paratracheal lymph nodes (stations 2R, 2L), right paratracheal lymph nodes (station 4R), and left paratracheal lymph nodes superior to the aortic arch (station 4L). The anterior subcarinal (station 7) and bilateral hilar nodes (stations 10R, 10L) may be accessible but are technically challenging (figure 3). The nodes can be sampled or removed entirely for histologic evaluation.

The goal of mediastinoscopy for staging lung carcinoma patients is to obtain samples of all accessible lymph node stations: 2L, 2R, 4L, 4R, and 7. Microscopic lymph node metastasis can occur even in lymph nodes that appear grossly normal. A retrospective review of 215 patients undergoing mediastinal lymphadenectomy found that the incidence of occult N2 disease found at resection was 16 percent for patients who were N2/N3 node negative by integrated PET/CT [6]. Patients with metastases in lymph node stations contralateral to the lung tumor are upstaged to N3 disease rather than N2 ipsilateral mediastinal lymph nodes (see "Tumor, node, metastasis (TNM) staging system for lung cancer"). For patients with diseases other than lung carcinoma, the authors limit the lymph node stations biopsied to those that are abnormal by radiographic evaluation.

The authors prefer video-assisted mediastinoscopy because of the optical magnification provided by the video mediastinoscope and the improved ability for the surgeon's assistant to view the operative field. Optical magnification allows for safer dissection and efficient identification of critical neurovascular structures.

Prior lower neck surgery, particularly thyroid or parathyroid procedures, can create adhesions, which may obliterate the pretracheal space in the neck. The pretracheal space is generally not disturbed caudally by most neck procedures, and a cervical mediastinoscopy can be safely performed. However, in the clinical setting of a previous mediastinoscopy, the pretracheal space may contain dense adhesions. In this setting, the authors prefer to perform an endobronchial ultrasound with transbronchial fine needle aspiration biopsy. Because the pretracheal space is not opened during routine median sternotomy, prior sternotomy should not affect the ability to perform a cervical mediastinoscopy.

Thoracoscopy – Video-assisted thoracic surgery (VATS) is preferred by the authors to biopsy subaortic (station 5) and para-aortic (station 6) nodes. If the nodes are large and extend to the anterior chest wall, the authors prefer an anterior mediastinotomy. Thoracoscopy also allows the surgeon a much broader field of vision and the ability to rule out pleural dissemination. It also provides the ability to biopsy paratracheal (station 2), azygos (station 4R), paraesophageal (station 8), or pulmonary ligament (station 9) lymph nodes (figure 3). The nodes can be sampled or removed entirely for histologic evaluation. The authors biopsy lymph node stations identified on preoperative imaging as abnormal before proceeding to biopsy any other lymph nodes present.

Anterior mediastinotomy – An anterior mediastinotomy (Chamberlain procedure) is performed to biopsy para-aortic (station 6) and subaortic (station 5) nodes, as well as to biopsy an anterior mediastinal mass. The nodes can be sampled or removed entirely for histologic evaluation.

Endobronchial ultrasound – Endobronchial ultrasound can be performed to biopsy lymph nodes in stations 1 to 4, 7, and 10 to 12 (figure 3). The nodes are biopsied by a fine needle aspiration (FNA) approach through the trachea or bronchus (figure 4). (See "Endoscopic ultrasound-guided sampling of the mediastinum: Technique, indications, contraindications, and complications".)

Electromagnetic navigational bronchoscopy – Navigational bronchoscopy can also be used to biopsy lymph nodes in stations 1 through 4, 7, and 10 through 12 (figure 3). After the lymph node is located using electromagnetic navigation, it is also biopsied by transbronchial needle aspiration (TBNA) [7].

Esophageal ultrasound – Esophageal ultrasound is performed to biopsy subcarinal (station 7), paraesophageal (station 8), and pulmonary ligament (station 9) nodes. The biopsy is performed as an FNA. (See "Endoscopic ultrasound for evaluating patients with esophageal cancer".)

TECHNICAL APPROACHES — The technical approaches for a cervical mediastinoscopy, anterior mediastinotomy, and thoracoscopy are discussed here. The technical approaches to endoscopy are reviewed separately.

(See "Endobronchial ultrasound: Technical aspects" and "Overview of upper gastrointestinal endoscopy (esophagogastroduodenoscopy)", section on 'Procedure'.)

Preparation — Cervical mediastinoscopy, anterior mediastinotomy, and thoracoscopy are generally performed as outpatient operations under a general anesthetic, although thoracoscopy is a more extensive procedure requiring thoracostomy tube placement and typically an overnight admission.

Antibiotic prophylaxis is typically administered intravenously (table 1). (See "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Thoracic surgery'.)

In preparation for a cervical mediastinoscopy or anterior mediastinotomy, the patient is positioned supine, with a shoulder roll placed under the scapulae and the neck extended. Oxygen saturation is monitored by a right extremity pulse oximeter or a right radial arterial line that can also serve as an indirect assessment of brachiocephalic arterial compression. Because of the risk of embolization caused by innominate artery compression during mediastinoscopy, the authors consider a calcified innominate artery to be a contraindication to mediastinoscopy.

Vaginal gauze packing strips should be on the sterile field at all times. A median sternotomy saw and instruments should be in the operating room during all mediastinoscopies since median sternotomy is the preferred approach to control major bleeding from the innominate artery, aortic arch, and right pulmonary artery.

In preparation for a thoracoscopy, single lung ventilation is performed via a double lumen endotracheal tube or a bronchial blocker, depending on the anesthesiologist and surgeon's preference. The patient is placed in the lateral decubitus position and secured in place with tape and/or a sandbag. The operating room table is flexed to prevent the hip from interfering with the instruments and camera, as well as to open the intercostal spaces.

Gross appearance of nodes — Normal and inflammatory lymph nodes in the mediastinum are rubbery and pearly white to gray; those affected by anthracosis are typically grayish black while those involved with metastatic disease from the lung or other solid tumors are hard and often have a whitish appearance. The gross appearance of a lymphomatous node is gray and firm, though often not hard. Granulomatous lymph nodes, as in sarcoidosis, are typically yellow in color and hard. If there is doubt as to the nature of a given structure, an aspiration with a 22 gauge needle should be performed prior to a biopsy. A bloodless aspirate is not confirmation that the structure is not a vessel. Matted nodes may be densely adherent to blood vessels. Simple excision of normal-appearing fat is unlikely to yield concealed lymph nodes.

Mediastinoscopy — A midline transverse incision is made immediately above the clavicular heads. The incision is carried through the platysma, between the strap muscles (sternothyroid, sternohyoid, thyrohyoid, and omohyoid muscles), and down to the anterior surface of the trachea, where the pretracheal plane is entered. Once this plane is identified, blunt finger or direct video dissection is used to develop this plane distally [5].

Small blood vessels that disrupt the course of dissection can be secured with 5 mm laparoscopic hemostatic clips or electrocauterized. Extreme caution must be exercised when using cautery in the mediastinum and major structures, such as the left recurrent laryngeal nerve, trachea, and great vessels, and the barrel of the mediastinoscope and other instruments must be avoided. Mediastinoscopy biopsy forceps are used to sample the nodal tissue or remove small, intact nodes.

The strap muscles and the platysma are closed using serial layers of absorbable suture prior to skin closure, to avoid adherence of the trachea directly to the skin and in case the patient requires a future cervical incision.

In our institution, we proceed with a resection of a lung cancer in the same setting as the mediastinoscopy if the frozen section of N2 and N3 nodes is negative for metastatic disease. In situations of equivocal frozen section results or for disease other than lung cancer, the surgeon and pathologist must be satisfied with the amount of tissue sampled, and the surgeon may prefer to wait for permanent results prior to performing a pulmonary resection. A retrospective study of 122 patients with bronchogenic carcinoma who underwent cervical mediastinoscopy reported a false negative rate of 1.6 percent, sensitivity of 94.6 percent, and a specificity of 100 percent [8].

Anterior mediastinotomy — A transverse incision is made immediately lateral and to the left of the sternum at the angle of Louie, along the second costal cartilage. The laterality and cartilage chosen may vary if an anterior mediastinal mass is being biopsied, depending on the entry point that will allow the best access to the tumor. The incision is carried between the pectoralis fibers down to the second costal cartilage, which is incised along its midpoint from the sternum to the costochondral junction. The perichondrium is dissected circumferentially from the costal cartilage using a periosteal elevator, and the costal cartilage is excised flush with the sternum medially and at the costochondral junction laterally. The internal mammary artery is swept laterally and the mediastinum is entered medially; this technique minimizes the chances of entering the pleura and causing a pneumothorax.

After identifying the node or tumor, biopsies are performed by grasping a portion of the mass and excising it with scissors or a scalpel. Alternatively, mediastinoscopy biopsy forceps can be used to obtain specimen.

The perichondrium can be closed at the surgeon's discretion, and the muscle and subcutaneous tissues are reapproximated. If the pleura has been entered, as evidenced by air bubbles emerging when irrigation is placed into the wound, a red robin catheter is placed through the wound into the mediastinum and attached to suction as the wound is closed around it. When the running subcutaneous layer is completed, it is left untied. The catheter is then removed while the suture is tightened, preventing air from reentering the chest. The suture is tied and the skin is closed.

Thoracoscopy — An incision for the port for the thoracoscope is typically placed in the anterior axillary line near the diaphragm. A utility incision is made in the third, fourth, or fifth interspace, and in the anterior axillary line. An additional working port may be created below the inframammary crease medially to facilitate exposure [9,10]. Biopsy of the 2R and 4R lymph node stations requires that the overlying mediastinal pleura be carefully incised lateral to the right phrenic nerve to avoid injuring the nerve. The left recurrent laryngeal nerve must be visualized and preserved when performing a biopsy of levels 5 and 6 lymph nodes.

COMPLICATIONS OF MEDIASTINOSCOPY — Because of the close proximity of the mediastinal nodes to major blood vessels and critical structures, intraoperative complications such as life-threatening hemorrhage and tracheal tear can occur. The most commonly injured blood vessels that require a median sternotomy for definitive control include the azygous vein, pulmonary artery, and innominate artery [11]. Injury to the left recurrent laryngeal nerve produces vocal cord palsy [12].

The morbidity and mortality of a mediastinoscopy are relatively low [13-15]. In a large retrospective review of 2137 patients, of whom 1745 underwent mediastinoscopy for known or suspected lung cancer, there were 12 complications (0.6 percent) and four perioperative deaths (0.2 percent) [13]. In another single-institutional review, the overall morbidity and mortality of the procedure were similarly low at 1.07 and 0.05 percent, respectively [14]. The most frequent complications included:

Recurrent laryngeal nerve injury – 12 patients (0.55 percent)

Hemorrhage – 7 patients (0.33 percent)

Tracheal injury – 2 patients (0.09 percent)

Pneumothorax – 2 patients (0.09 percent)

Of the seven patients who experienced hemorrhage, five were the result of a biopsy of lower paratracheal nodes (station 4), and one death resulted from injury to the pulmonary artery.

Injury to the esophagus is extremely rare. With the mediastinoscope anterior to the trachea, the esophagus is protected; however, an anterior wall perforation can occur with overly aggressive biopsy of the subcarinal lymph node station [16].

Prevention — The great vessels (eg, innominate vein, pulmonary arteries, azygous vein), trachea, esophagus, and recurrent laryngeal nerves must be identified during mediastinoscopy to avoid injury. The best preventive methods include clear identification of the node to be biopsied and its relationship to the adjacent structures, plus meticulous biopsy technique.

The following nodal stations and structures require particular attention during dissection (figure 3):

Upper and lower paratracheal nodes (stations 2 and 4) – Structures that can be damaged during the initial pretracheal dissection and biopsy of the upper paratracheal nodes include the aorta, the innominate vein, superior vena cava, and the trachea. The aortic arch crosses the trachea transversely, and the innominate artery arises from the left side of the aortic arch and crosses the trachea obliquely to the right. The superior vena cava, which lies on the right anterior surface of the lower trachea, should be identified and protected during right paratracheal dissection, as well as the azygous vein, which travels from anterior to posterior on the right side of the lower trachea.

The left recurrent laryngeal nerve, located lateral and parallel to the trachea, is in close approximation to the paratracheal nodes [17]. The nerve must be identified and preserved prior to performing an upper or lower paratracheal node biopsy.

Para-aortic lymph nodes (station 5) – The right pulmonary artery (PA) passes transversely over the distal tracheal and subcarinal area. Overly aggressive traction on lymph nodes in this area can damage the PA, which is thin walled and fragile. The left phrenic nerve must also be identified and avoided during instrumentation of the para-aortic lymph nodes, particularly when approaching the area by left anterior mediastinotomy.

Subcarinal and paraesophageal lymph nodes (stations 7 and 8) – The esophagus lies immediately posterior to the subcarinal lymph nodes (station 7) and between the paraesophageal nodes (station 8) and is at risk for injury or perforation. The biopsy should clearly contain only nodal tissue; the presence of skeletal or smooth muscle should alert the surgeon to possible esophageal injury, which should prompt an esophagoscopy if recognition occurs in the operating room while the patient is still anesthetized. Otherwise, a contrast esophagram should be performed.

Hilar lymph nodes (station 10R) – This lymph node station is not routinely biopsied by most thoracic surgeons, though it is reasonably easy and safe to access by using the video mediastinoscope, particularly on the right. The anterior trunk of the right PA is often encountered during dissection of the right hilar (tracheobronchial angle, station 10R) nodes.

Management

Life-threatening hemorrhage — The first maneuver to control hemorrhage is to pack vaginal gauze strips through the mediastinoscope in an attempt to tamponade the bleeding. The surgeon should not remove the mediastinoscope from the pretracheal space, as this may displace the packing and prevent the surgeon from identifying the source of bleeding again [11].

If packing achieves hemostasis, the packing is left in place for a minimum of 10 to 30 minutes. The packing is gently removed and the site is reinspected for bleeding. If large amounts of bleeding persist, the packing is replaced and the process repeated. However, if bleeding persists despite multiple attempts at packing, or if the bleeding overwhelms attempts at packing, the surgeon must obtain definitive control of bleeding, typically by median sternotomy. If the patient is stable and can be repositioned, a right thoracotomy may provide superior exposure for controlling hemorrhage from the azygous vein, posterior superior vena cava, or segmental pulmonary artery injuries [11]. (See "Overview of blunt and penetrating thoracic vascular injury in adults".)

Following the median sternotomy or right thoracotomy and effective control of hemorrhage, the definitive resection of the pulmonary lesion may be performed if the patient is hemodynamically stable and the mediastinal lymph nodes are negative for metastatic disease by frozen section analysis. However, a left lower lobectomy is challenging through a median sternotomy.

Tracheal injury — Tracheal injuries can occur during the insertion of the mediastinoscope or dissection. Proximal tracheal tears typically occur during the initial dissection and entry into the pretracheal plane. They are confirmed by submerging the exposed trachea under water and observing for air bubbles.

If the tracheobronchial tree is injured within the mediastinum, the mediastinal space is contaminated. Depending on the extent of the injury, open repair of the trachea is indicated, as well as drainage of the mediastinum. If the injury to the trachea is at the entry point of the mediastinoscope, then the repair is performed through the original incision [18].

Tracheal injuries are closed with absorbable suture (classically simple, interrupted Vicryl sutures), tying tightly enough to create an airtight closure, but not tearing the tracheal cartilages. Leaving a Blake or Jackson-Pratt drain over the tracheal repair within the pretracheal space allows the surgeon to confirm that the tracheal repair remains airtight on postoperative day 1, as shown by the drain retaining bulb suction.

Esophageal injury — If there is any question regarding a potential esophageal injury, an immediate esophagoscopy is performed. If negative, a contrast esophagram should be performed. The management of an iatrogenic esophageal perforation is discussed separately. (See "Surgical management of esophageal perforation", section on 'Principles of surgical management'.)

Pneumothorax — Many surgeons obtain a postoperative chest radiograph routinely. A small violation of the mediastinal pleura may cause a pneumothorax that will resolve with time. If a pneumothorax is recognized intraoperatively, the surgeon may insert a suction catheter into the defect and aspirate the air prior to final skin closure. In contrast, a pneumothorax that occurs due to a lung parenchymal injury is more likely to be associated with increased peak inspiratory pressures, tracheal shift, distant breath sounds, hypotension, and cyanosis. Such signs are indicators that a closed tube thoracostomy is required for immediate decompression. (See "Thoracostomy tubes and catheters: Indications and tube selection in adults and children".)

Recurrent laryngeal nerve injury — An injury to the recurrent laryngeal nerve (RLN) is typically diagnosed postoperatively by the symptoms of new, unresolving hoarseness, dysphonia, limited phonation time, or vocal fatigue (figure 5 and figure 6). The most common type of RLN injury following a mediastinoscopy is unilateral and left sided [19,20]. (See "Surgical anatomy of the thyroid gland", section on 'Recurrent laryngeal nerve' and "Hoarseness in adults", section on 'Neurologic dysfunction'.)

No treatment is required for unilateral vocal cord palsy after mediastinoscopy, as it will spontaneously resolve in at least 50 percent of patients within one year [20]. In the setting of a permanent vocal cord injury, the planned resection of the pulmonary lesion should be performed prior to a thyroplasty to avoid damaging a vocal cord repair by a double lumen endotracheal tube required for the thoracic procedure. Prior to resection, the patient with permanent vocal cord injury should undergo vocal cord injection to prevent aspiration post pulmonary resection.

COMPLICATIONS OF ANTERIOR MEDIASTINOTOMY — Anterior mediastinotomy is a more invasive procedure than mediastinoscopy and hence carries a higher risk of morbidity and mortality compared with mediastinoscopy [21]. In a retrospective review of 117 consecutive patients undergoing an anterior mediastinotomy, the morbidity rate was 6.8 percent and there was no mortality attributed to the procedure [15]. Intraoperative complications included hemorrhage (n = 1), pneumothorax (n = 1), injury to the recurrent laryngeal nerve (n = 1), and hypoxia (n = 2). Injury to the internal mammary artery and/or aorta, while uncommon, can result in life-threatening hemorrhage. Phrenic nerve injuries have also been reported.

The authors routinely obtain a postoperative chest radiograph to assess for a pneumothorax. A symptomatic pneumothorax is treated with a thoracostomy tube. Those that are not symptomatic are treated expectantly.

COMPLICATIONS OF THORACOSCOPY — Massive bleeding from an artery or vein is an uncommon but life-threatening complication of thoracoscopy. Conversion from a thoracoscopic (VATS) procedure to an open thoracotomy occurs in as many as 22 percent of procedures [10]. Other possible complications include chylothorax, pneumothorax, phrenic nerve injury, left recurrent laryngeal nerve injury, and esophageal perforation [9].

These possible complications highlight the fact that with thoracoscopy, as with all technology and skill sets, education, practice, and a learning curve necessarily accompany performance of the procedure. Management of hemorrhage and other possible injuries is reviewed separately. (See 'Management' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and management of lung cancer".)

SUMMARY AND RECOMMENDATIONS — The evaluation of mediastinal nodes is paramount for staging patients with suspected or proven bronchogenic carcinomas and for diagnosing primary and secondary malignancies involving mediastinal lymph nodes.

Mediastinoscopy can be performed with video-assisted or direct optic visualization and is used to biopsy upper paratracheal lymph nodes (stations 2R, 2L), right paratracheal lymph nodes (station 4R), and left paratracheal lymph nodes superior to the aortic arch (station 4L). (See 'Selection of biopsy procedure' above.)

Thoracoscopy is used to biopsy subaortic (station 5) and para-aortic (station 6) nodes. If the nodes are large and extend to the anterior chest wall, the authors prefer an anterior mediastinotomy. Thoracoscopy can also be performed to biopsy azygos (station 4R), paraesophageal (station 8), or pulmonary ligament (station 9) lymph nodes. (See 'Selection of biopsy procedure' above.)

An anterior mediastinotomy (Chamberlain procedure) is performed to biopsy para-aortic (station 6) and subaortic (station 5) nodes, as well as to biopsy an anterior mediastinal mass. (See 'Selection of biopsy procedure' above.)

The major risks and complications of mediastinoscopy and biopsy include life-threatening hemorrhage, and injury to the trachea, esophagus, and left recurrent laryngeal nerve. (See 'Complications of mediastinoscopy' above.)

A median sternotomy should be performed to control hemorrhage resulting from a mediastinoscopy if packing with vaginal gauze strips through the mediastinoscope is not effective. (See 'Life-threatening hemorrhage' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Adam J Braze, DO, who contributed to earlier versions of this topic review.

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References

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