MEDIASTINOSCOPY, THORACOSCOPY, AND VIDEO-ASSISTED THORACIC SURGERY IN THE DIAGNOSIS AND STAGING OF LUNG CANCER

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MEDIASTINOSCOPY, TMORACOSCOPY, AND VIDEOASSISTED THORACIC SURGERY IN THE DIAGNOSIS AND STAGING OF LUNG CANCER Steven J. Mentzer, MD

The intrathoracic staging of lung cancer has evolved to include information obtained from bronchoscopy, mediastinoscopy, and thoracoscopy. Through the use of imaging studies to guide the application of these techniques, valuable staging information can be obtained to facilitate planning for multimodality therapy. Bronchoscopy, mediastinoscopy, and video-assisted thoracoscopic techniques can provide histologic sampling of the primary tumor and potential metastatic sites. Equally important, this information can be obtained while limiting the morbidity of surgical staging. Surgical staging of the primary tumor is determined primarily by the location of the tumor (Table 1). Primary tumors are staged as T3 or T4 independent of size, but dependent on the relative resectability of the contiguous tissue structures.13Tumors that directly invade the chest wall, diaphragm, mediastinal pleura, or parietal pericardium are considered potentially resectable and are clinically staged as T3. T3 tumors Supported in part by NIH Grant HL47078 ~

From the Division of Thoracic Surgery, Brigham and Women's Hospital; the Dana-Farber Cancer Institute; and Harvard Medical School, Boston, Massachusetts ~

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HEMATOLOGY/ONCOLOGY CLINICS OF NORTH AMERICA VOLUME 11 * NUMBER 3 * JUNE 1997

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Table 1. SURGICAL STAGING OF LUNG CANCER Clinicopathologic Stage Biopsy Findings

TN Designation

Stage

Hilar lymph nodes lpsilateral paratracheal lymph nodes Contralateral paratracheal lymph nodes Trachea or carina Unresectable structures (eg, aorta, vertebral body) Pleural disease

N1 N2

II IllA

N3

lllB

T4 T4

IllB IllB

T4

Ill6

also include tumors in the main stem within 2 cm (but not involving) of the carina or tumors that are associated with atelectasis or obstructive pneumonitis of the entire lung. Tumors that invade unresectable structures such as the heart, great vessels, trachea, esophagus vertebral bodies, or carina are staged as T4. Malignant effusions associated with an ipsilateral tumor are also considered stage T4. The stage grouping defined by the American Joint Committee on Cancer (AJCC) has included T3 tumors in stage IIIA and T4 tumors in stage IIIB in the absence of distant metastases.', l5 Because of the success of surgery in treating many T3 tumors without metastatic disease, the stage grouping of T3 tumors is currently being re-examined. The most common sites of metastatic spread of lung cancer are the contiguous lymph nodes in the lung and mediastinurn. The segmental lymph nodes are commonly the first site of regional lymph node metastases. Involvement of the ipsilateral segmental and peribronchial lymph nodes is classified as N1 disease. These lymph nodes are within the visceral pleural envelope and are potentially resectable with an anatomic lung resection. Metastases beyond the visceral pleura are usually found in the ipsilateral mediastinal and/or subcarinal lymph nodes. Lymph node metastases in these areas are considered N2 disease. Progression of the nodal metastases to the contralateral mediastinum or either scalene or supraclavicular lymph node areas is considered N3 disease. The AJCC stage groupings have included N2 disease in stage IIIA and N3 disease in stage 1IIB.l. l5 The prognosis of patients with stage I11 disease, in the absence of multimodality therapy, is poor. Although clinical series staging patients radiographically have reported 3-year survival greater than 30%? lo studies using mediastinoscopy to document stage I11 disease have estimated the actuarial 3-year survival to be below 20%.18,l9 The prognostic uncertainty of patients with mediastina1 lymph node metastases led Naruke and colleagueslbto propose a lymph node map-

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ping schema. The proposed lymph node map documented the potential sites and level of lymph node metastases based on 270 patients who had undergone radical resection followed by careful pathologic examination. The lymph node map and numbering system has been widely adopted as a practical method for identifying the lymph node groups in the lung and mediastinum. The lymph node map also provides a useful method of recording and classifying the extent of lymph node metastases assessed both radiographically and pathologically. The original lymph node map has been refined by the American Thoracic Society2(Fig. 1). The radiographic evaluation of a patient with lung cancer typically involves CT scans. These scans are potentially useful in evaluating both the primary tumor and the potential sites of spread. CT scans of the primary tumor can identify contiguous structures and areas of potential invasion, but they are relatively insensitive at detecting invasion as compared with surgical staging5In the evaluation of lymph node metastases, CT scanning has demonstrated sensitivity of 79% for mediastinal adenopathy. The specificity for metastatic lung cancer, however, drops to 65% when compared with surgical staging.20These findings suggest

Figure 1. The American Thoracic Society lymph node map demonstrating the anatomic boundaries between lymph node stations (Modified from American Thoracic Society: Medical section of the American Lung Association. Clinical staging of primary lung cancer. Am Rev Respir Dis 127:659-664, 1983; with permission.)

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that CT scanning can be most useful in providing a preliminary assessment of clinical stage that can be confirmed by a minimally invasive staging procedure. Several instruments are available for minimally invasive staging procedures. Fiberoptic bronchoscopy can be performed on an outpatient basis with topical anesthesia or in conjunction with a surgical procedure under general anesthesia. Bronchoscopy can provide a visual assessment of endobronchial primary tumors as well as evaluate the possibility of a second primary tumor. Masses that involve the trachea or carina can be immediately staged as T4 (stage IIIB).'" Similarly, lung cancers extending to the lobar orifice may suggest the consideration of sleeve lobectomy or pneumonectomy. The visual assessment of the primary tumor can also provide a clinically useful estimate of the probability of tumor complications such as airway obstruction, postobstructive pneumonia, and/or hemoptysis. Bronchoscopy can also be used to obtain a tissue or cytologic diagnosis. Bronchoscopy has a more limited role in the assessment of mediastinal lymph nodes. Enlarged peribronchial lymph nodes may be suggested by extrinsic airway compression. Similarly, a widened carina may suggest subcarinal lymphadenopathy. In patients with subcarinal adenopathy, transcarinal needle biopsy has been used as a supplement to conventional broncho~copy.~, *l Bronchoscopic needle aspirates are limited by the small cytologic sample, and the use of this procedure is usually restricted to large subcarinal masses.

MEDIASTINOSCOPY

The typical mediastinoscope is a rigid instrument with a handle and central working channel equipped with a light to illuminate the area distal to the instrument. The central working channel is used to facilitate lymph node dissection and biopsy. Cervical mediastinoscopy requires an incision in the suprasternal notch to obtain access to the pretracheal fascia. The pretracheal fascia defines an avascular potential space that permits access to the distal trachea and main stem bronchi. To facilitate exposure to the suprasternal notch, the mediastinoscope requires maximal head extension. Because of the degree of head extension and the requirement for complete relaxation, the procedure is performed under general anesthesia. In most centers, mediastinoscopy is performed as an outpatient procedure requiring only a few hours in the hospital. Cervical mediastinoscopy is the most common mediastinoscopic procedure. The mediastinoscope is advanced in the pretracheal space to the left and right main stem bronchi. The lymph nodes at the tracheo-

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bronchial angle (1OL and 10R) are readily accessible within the pretracheal fascia. The upper (2L and 2R) and lower (4L and 4R) lymph nodes are located outside of the pretracheal fascia and require dissection through the fascia for exposure of these lymph node groups. Similarly, access to the subcarinal lymph nodes requires dissection through the pretracheal fascia for exposure and biopsy. In most cases, cervical mediastinoscopy can be performed after previous median sternotomy or mediastinal radiation. The left lung has relatively complex lymphatic drainage. In addition to left paratracheal lymph nodes, there are mediastinal or N2 lymph nodes located in the aorticopulmonary (AP) window. Access to the AP window through a cervical incision is limited by the aorta and the long left main stem bronchus. AP window lymph nodes are particularly important in patients with lymphadenopathy demonstrated by imaging studies or in patients with left upper lobe cancers. In left upper lobe cancers, the AP window lymph nodes (levels 5 and 6) represent the first site of nodal metastases outside of the visceral ~1eura.I~ Access to the AP window can be obtained with the mediastinoscope using two techniques: extended or anterior mediastinoscopy. Extended mediastinoscopy is performed through a typical cervical mediastinoscopy incision. The extended mediastinoscopy, therefore, permits routine access to the paratracheal lymph nodes. In addition to the paratracheal lymph nodes, the AP window lymph nodes (level 5 and 6) can be accessed by advancing the mediastinoscope over the aorta between the innominate artery and the carotid artery! The mediastinoscope is generally directed toward the preaortic (level 6) lymph nodes. Access to the subaortic (level 5) lymph nodes can be obtained with downward traction on the aorta. Because of the necessary manipulation of the aorta, extended mediastinoscopy is generally contraindicated in aortas with atherosclerotic or inflammatory disease. A more common approach to the AP window is anterior or parasternal mediastinoscopy performed through a parasternal mediastinotomy. The anterior or parasternal mediastinoscopy procedure is similar to the "Chamberlain" procedure described by McNeill and Chamberlain." The incision for anterior mediastinoscopy is typically placed in the bed of the left second costal cartilage or the second rib interspace. A plane of dissection is developed within the mediastinal pleura to the AP window. The preaortic (level 6) lymph nodes can be palpated at the base of the innominate artery. Subaortic (level 5) lymph nodes are usually palpated next to the phrenic and vagus nerves in the subaortic space. Anterior mediastinoscopy does not permit access to the posterior mediastinal lymph nodes in the area of the distal left main stem bronchus or anterior lymph nodes occasionally found near the superior pulmonary vein. Mediastinoscopy is a generally safe procedure with morbidity lim-

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ited to incisional discomfort. Transient hoarseness in the area of the incisions is occasionally seen after cervical mediastinoscopy. It is the result of a left paratracheal dissection or occurs after the use of electrocautery near the left recurrent nerve. Bleeding is infrequent during paratracheal or AP window lymph node dissections. Because the bronchial arteries course through the subcarinal space, dissection of the level 7 lymph nodes is occasionally associated with arterial bleeding. This bleeding is usually controlled with electrocautery or direct compression. Venous bleeding is usually associated with injury to the azygous vein and can require an anterior thoracotomy for repair. Infection is extremely rare even in patients receiving immunosuppressive therapy. Pneumothorax can be observed after transpleural anterior mediastinoscopy. The pleural air is generally not associated with injury to the lung and can be aspirated prior to closing the incision.

THORACOSCOPY In the 1920s, the thoracoscope was developed to facilitate the drainage of pleural empyemas and the lysis of tuberculous adhesions.6, The recent popularity of thoracoscopy has been stimulated by improved video optics and thoracoscopic instrumentation. The advantage of the thoracoscope is that it limits the incisional pain associated with standard thoracotomy.'2 Thoracoscopy is performed through one or more limited incisions or "access ports" in the intercostal spaces. The thoracoscopy ports are generally sized to permit digital access to the hemithorax. With these small access ports, patients have less pain than through standard thoracotomy incisions. Because there is minimal muscular injury, patients can soon resume normal activities. The disadvantage of thoracoscopy is that it usually requires general anesthesia and single-lung ventilation. The video thoracoscope provides a panoramic view of the ipsilateral hemithorax including the hilum mediastinum, visceral pleura, and chest wall. In cases with a peripheral primary tumor less than 3 cm (Tl), thoracoscopy can facilitate the limited resection of the tumor. Frozensection evaluation of the lesion can provide an intraoperative tissue diagnosis. In appropriate cases of non-small cell carcinoma, thoracoscopy can also facilitate staging of the ipsilateral hilum and paratracheal lymph nodes. In the right hemithorax, the thoracoscope can provide direct visualization of the right paratracheal lymph nodes cephalad to the azygous vein (levels 4R and 2R) lying just beneath the mediastinal pleura. Also, the occasional periazygous lymph node can be readily visualized and biopsied. In the left hemithorax, the video thoracoscope provides visualiza-

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tion of the preaortic (level 6) and subaortic (level 5) lymph node groups. In addition, several lymph node groups not accessible through anterior mediastinoscopy can be visualized and biopsied. These lymph nodes are occasionally present in the posterior mediastinum near the distal left main stem bronchus and anterior mediastinum at the level of the superior pulmonary vein. An advantage of video thoracoscopy in both hemithoraces is that the inferior pulmonary ligament lymph nodes (level 9) can be biopsied. The inferior pulmonary ligament lymph nodes may be important in staging select patients with lower lobe lung cancers (J. Roberts et al, manuscript in preparation). Thoracoscopy can also demonstrate occasional pleural nodularity in tumors with lymphatic invasion, such as diffuse bronchoalveolar carcinoma. Pleural "studding" can be seen even in the absence of radiographic thickening or pleural effusion. Finally, the suggestion of chest wall or mediastinal invasion can be directly assessed with the video thoracoscope.

VIDEO-ASSISTED THORACIC SURGERY

Video-assisted thoracic surgery (VATS) is a more inclusive term than thoracoscopy. In practice, VATS can describe thoracoscopic procedures as well as surgical procedures that involve variable combinations of the thoracoscope and standard thoracotomy instruments. The enhanced video optics and improved thoracoscopic instrumentation have led to these tools being used with greater frequency in routine general thoracic surgery. The use of VATS in the diagnosis and staging of lung cancer can be illustrated with an indeterminate peripheral lung nodule. The peripheral lung nodule can be excised thoracoscopically to permit a tissue diagnosis. The diagnosis of a benign lesion, such as granulomatous disease, means that cultures are obtained but no further surgery is performed. Alternatively, the identification of a primary lung cancer indicates that further intrathoracic staging should be performed. The hilar and paratracheal lymph nodes are sampled. The absence of metastatic disease in these lymph nodes suggests that a completion lobectomy could be performed under the same single-lung anesthetic. In many cases, the lobe can be resected using video-assisted techniques. In our experience, peripheral lung lesions associated with minimal pleural adhesions and partially complete fissure can be resected using a VATS anatomic lobectomy technique. This lobectomy is indistinguishable from the lobectomy performed with open technique in terms of morbidity, blood loss, and operating time (J. Roberts et al, manuscript in preparation). The typical

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lobectomy is performed using a single 40-mm incision over the major fissure with two to three accessory access ports.

Staging of Specific Tumors Minimally invasive staging of right upper lobe tumors can be approached with either thoracoscopy or mediastinoscopy. A typical presentation is a CT scan demonstrating a solitary pulmonary nodule, that is, a pulmonary nodule less than 3 cm in diameter in the peripheral lung field. Because the appearance of the nodule is indeterminate, a tissue diagnosis should be obtained. Thoracoscopy can provide an excisional wedge resection. Frozen section of the tumor suggests a malignancy. The preliminary finding of lung cancer can be evaluated by staging of the hilum and right paratracheal lymph nodes (solid black in Figure 2). The biopsy of ipsilateral lymph nodes will often document the presence of occult stage IIIA lung cancer. The incidence of so-called skip metastases to the contralateral mediastinum is unknown, but it is generally considered infrequent. A second approach to staging a patient with a right upper lobe tumor is cervical mediastinoscopy. A right upper lobe tumor that is

Figure 2. A right upper lobe tumor. The lymph nodes accessible by a thoracoscopic staging procedure are shown (solid black).

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greater than 3 cm and has a spiculated appearance in the setting of a long-term smoker has a high probability of being non-small cell lung cancer. CT evaluation of the chest may suggest right paratracheal adenopathy. Both the size of the tumor and the enlarged paratracheal lymph nodes increase the probability that the patient has lymph node metastases. Given the possibility of stage IIIA lung cancer, the staging issues are (1)providing a tissue diagnosis of stage IIIA disease, and (2) excluding the presence of contralateral (stage IIIB) lymph node metastases. Cervical mediastinoscopy provides a minimally invasive assessment of the ipsilateral and contralateral lymph nodes (solid black in Figure 3). The procedure can be performed on an outpatient basis with minimal morbidity. This is an important consideration because the cervical mediastinoscopy procedure should not delay the beginning of systemic therapy. The left upper lobe mass provides a unique challenge for surgical staging because the lymphatic drainage includes both the AP window and the paratracheal lymph nodes. The traditional approach to surgical staging of this tumor is a combination of cervical and anterior mediastinoscopy. Cervical mediastinoscopy provides access to the paratracheal lymph nodes and can exclude the presence of stage IIIB contralateral lymph node metastases (solid gray Zyrnph nodes in Figure 4). Anterior

Figure 3. A right upper lobe tumor. The lymph nodes accessible by cervical mediastinoscopy are shown (solid black).

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Figure 4. A left upper lobe tumor. The lymph nodes accessible by anterior mediastinoscopy (levels 5 and 6 ) are shown as a single site (solid black). The relevant lymph nodes accessible by cervical rnediastinoscopyare also shown (solid gray).

mediastinoscopy provides access to the AP window (solid black in Fig. 4), which is considered the first site of metastatic spread. This approach is typically reserved for left upper lobe tumors with a high likelihood of being non-small cell lung cancers. Thoracoscopy is a complementary procedure to mediastinoscopy for the staging of left upper lobe tumors. Thoracoscopy is particularly useful in indeterminate peripheral lesions. The thoracoscope and appropriate thoracoscopic instrumentation can provide a histologic diagnosis as well as an assessment of nodal metastases. Thoracoscopy provides excellent visualization of the AP window and the preaortic area. In many cases, the anterior hilum can be readily dissected, providing tissue diagnosis of the lymph nodes representing the transition between N1 and N2 disease (solid black in Figure 5). Lower lobe tumors have been typically staged by cervical mediastinoscopy. The cervical mediastinoscopy procedure permits access to the subcarinal lymph nodes as well as the left and right paratracheal lymph nodes. Because the subcarinal space is usually the first site of N2 metastases, cervical mediastinoscopy is a good approach for known non-small cell lung cancer. Thoracoscopy provides useful information in a subset of right lower lobe tumors (Fig. 6). First, thoracoscopy can provide a tissue diagnosis in tumors that have an indeterminate probability of

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Figure 5. A left upper lobe tumor. The lymph nodes accessible by thoracoscopic staging are shown (solid black).

Figure 6. A right lower lobe tumor. The lymph nodes routinely accessible by thoracoscopic exploration are shown (solid gray). In some patients, subcarinal lymph nodes may also be accessible.

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being lung cancer. Second, a subset of right lower lobe tumors will develop selective lymph node enlargement in the inferior pulmonary ligament. Lymphadenopathy in the inferior pulmonary ligament (level 9) lymph nodes can be seen on CT scan of the chest, but it is not accessible by cervical mediastinoscopy. Thoracoscopy provides direct access to the ligament and level 9 lymph nodes. Finally, the thoracoscope can be used to dissect the major fissure and provide access to the N1 or sump” lymph nodes along the bronchus intermedius. Thus, thoracoscopy and mediastinoscopy can be used as complementary procedures to provide tissue biopsies for diagnosis and staging information. The appropriate application of these techniques can improve diagnostic accuracy while limiting surgical morbidity. I,

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17. Patterson GA, Piazza D, Pearson FG, et al: Significance of metastatic disease in subaortic lymph nodes. Ann Thorac Surg 43:155-159, 1987 18. Pearson FG: Staging of the mediastinum. Role of mediastinoscopy and computed tomography. Chest 103:3465-348S, 1993 19. Pearson FG, DeLarue NC, Ilves R, et al: Significance of positive superior mediastinal nodes identified at mediastinoscopy in patients with resectable cancer of the lung. J Thorac Cardiovasc Surg 83:l-11, 1982 20. Staples CA, Muller NL, Miller RR, et al: Mediastinal nodes in bronchogenic carcinoma: Comparison between CT and mediastinoscopy. Radiology 167367-372, 1988 21. Wang KP, Haponik EF, Britt EJ, et al: Transbronchial needle aspiration of peripheral pulmonary nodules. Chest 86:819-823, 1984

Address reprint requests to Dr. Steven J. Mentzer Division of Thoracic Surgery Brigham & Women’s Hospital 75 Francis Street Boston, MA 02115