Diffuse malignant pleural mesothelioma is a rare aggressive cancer associated with asbestos exposure. Approximately 2000 to 3000 cases occur annually. The natural history is defined by a median survival of 4 to 12 months with no treatment. Difficulties in diagnosis, staging, and treatment have made mesothelioma a challenging entity for most clinicians.

In the 1940s, Sarot¹ first described the technique of extrapleural pneumonectomy (EPP) for tuberculous empyema. In the 1980s, the operation was applied to diffuse malignant pleural mesothelioma and later to other malignancies, including locally advanced lung cancer and thymoma. In 1976, Butchart and associates reported a prohibitive operative mortality of 31%, but other series have reported a mortality range of 6% to 13%.² In the 1990s, significant improvements in mortality rates were achieved. In 1999, our institution reported the lowest published operative mortality of 3.8%.³ A retrospective study of our results from the Brigham and Women’s Hospital/Dana Farber Cancer Institute was reported, representing the largest single-institution review of 328 patients with mesothelioma who underwent EPP between 1980 and 2000. With further experience, our operative mortality declined to 3.4%.⁴

The significant improvement in perioperative mortality has been attributed to continuous refinements in technique and aggressive prevention and treatment of complications.^2,4 However, defined criteria for patient selection and comprehensive preoperative assessment also have contributed to the improvement in surgical results.

To be considered a candidate for EPP, a patient must meet several preoperative criteria (Table 122-1). The patient must have a Karnofsky performance status of greater than 70, normal liver and renal function tests, a room air arterial Pco₂ of less than 45 mm Hg, and a room air arterial Po₂ of greater than 65 mm Hg. While there is no strict age limit, we are hesitant to perform EPP in patients older than 70 years of age. A pulmonary function test that reveals a forced expiratory volume in 1 second (FEV₁) greater than 2 L is considered adequate for pneumonectomy. Quantitative ventilation/perfusion scan is indicated if the FEV₁ is less than 2 L. The combination of ventilation/perfusion scan and preoperative FEV₁ is used to predict postoperative lung function. Patients with a predicted postoperative FEV₁ of greater than 0.8 are acceptable candidates for EPP. Patients with a predicted postoperative FEV₁ of less than 0.8 L are considered for pleurectomy and decortication (see Chapter 121).

Echocardiography provides valuable information, including assessment of ventricular function, chamber size, wall motion abnormalities, valvular disease, and pulmonary artery pressure. Echocardiographic evidence of pulmonary hypertension warrants a right heart catheterization for direct pulmonary artery pressure measurement. The presence of pulmonary hypertension is a contraindication to pneumonectomy. For patients considered to be inoperable on the basis of pulmonary hypertension, temporary balloon occlusion of the ipsilateral main pulmonary artery can be performed during catheterization to simulate pneumonectomy physiology. During balloon occlusion, the patient is monitored for hemodynamic instability.

Preoperative chest MRI and CT scanning are used routinely to determine the extent of disease and to rule out transdiaphragmatic abdominal extension, contralateral hemithorax involvement, and mediastinal invasion. The presence of locally advanced or distant disease to these areas precludes resection. Chest MRI has been shown to be a valuable complement to chest CT scanning in making this determination.⁵ However, chest MRI and CT scan can be unreliable in assessing chest wall invasion. As a result, exploration is performed in patients with questionable radiographic evidence of chest wall invasion and no radiographic evidence of distant disease. Extrathoracic chest wall invasion discovered at exploration is a contraindication to resection. Obvious radiologic demonstration of invasion into the chest wall or palpable tumor by examination is considered unresectable, and the patient is not offered exploration.

Chest MRI and CT scan can be misleading in assessing transdiaphragmatic peritoneal invasion because of the difficulty in distinguishing local tumor compression on the diaphragm versus true transdiaphragmatic invasion. Radiologic evidence of transdiaphragmatic extension, intra-abdominal tumor, or ascites is an indication for diagnostic laparoscopy or exploratory laparotomy to evaluate the peritoneal cavity.

Histologic diagnosis of mesothelioma by pleural biopsy is required before proceeding with resection. Although cytologic diagnosis is possible, the differentiation of mesothelioma from adenocarcinoma or sarcoma can be difficult. Surgical biopsy is considered the gold standard method for definitive diagnosis. Thoracoscopic pleural biopsy is generally performed via a single port along the incision line of the intended future thoracotomy. Radiologic suggestion of contralateral thoracic disease requires tissue confirmation by pleural or lung biopsy from the contralateral chest. Staging cervical mediastinoscopy is performed. If there is metastatic disease to the mediastinal lymph nodes, the patient should undergo induction chemotherapy followed by re-evaluation for surgical resection with restaging radiographic studies for an extent of disease work-up. In the absence of mediastinal involvement, the patient would proceed directly to surgical resection.

Anesthesia

A thoracic epidural catheter is placed preoperatively for intraoperative management and postoperative analgesia. Standard monitoring with telemetry, continuous pulse oximetry, central venous access, and urinary Foley catheterization are routinely used. After anesthetic induction, a left-sided double-lumen endotracheal tube is placed for single-lung ventilation, and the patient is positioned in the left lateral decubitus position for an extended right posterolateral thoracotomy. A nasogastric tube is placed, which facilitates identification of the esophagus during extrapleural dissection. It is left in place postoperatively to decompress the stomach and to prevent aspiration.

Surgical Management

EPP is performed in the following order: (1) incision and exposure of the parietal pleura; (2) extrapleural dissection to separate the tumor from the chest wall; (3) en bloc resection of the lung, pleura, pericardium, and diaphragm with division of the hilar structures; (4) radical lymph node dissection; and (5) reconstruction of the diaphragm and pericardium.^2,6,7

When there is preoperative radiologic evidence suggesting intra-abdominal disease, a limited subcostal incision is made along the line of the thoracotomy incision before proceeding with definitive resection. The diaphragm and peritoneal cavity are inspected for transdiaphragmatic involvement. Laparoscopic evaluation may be used as an alternative approach to an open subcostal incision. If there is evidence of intra-abdominal disease, histologic diagnosis is confirmed by biopsy, and the resection is aborted.

In the absence of intra-abdominal spread, an extended right posterolateral thoracotomy is performed (Fig. 122-1). The incision is started midway between the posterior scapular tip and the spine (inset) and extended along the sixth rib to the costochondral junction.⁶ The latissimus dorsi and serratus anterior muscles are both divided. The sixth rib is resected. The posterior periosteum in the bed of the sixth rib is incised, exposing the extrapleural plane.

Extrapleural dissection is performed with the use of blunt and sharp dissections initially in the anterolateral aspect followed by dissection to the apex. Anteriorly, the internal mammary vessels should be identified to prevent avulsion. If extensive chest wall invasion is discovered obliterating the extrapleural plane, surgical resection is precluded. In the absence of chest wall invasion, the extrapleural plane is extended, and previously dissected areas are packed with surgical pads for hemostasis. Along the thoracotomy, two chest retractors are positioned anteriorly and posteriorly to optimize exposure (Fig. 122-2). At the apex, care should be taken to avoid injury to the subclavian vessels (Fig. 122-3). The dissection is advanced over the apex of the lung, and the tumor is brought down from the posterior and superior mediastinum, where care should be attended to the azygos vein and superior vena cava (Fig. 122-4). After adequate exposure is obtained anterolaterally, posterior dissection is performed, with careful attention to the esophagus. If unexpected invasion of vital mediastinal structures (e.g., aorta, vena cava, esophagus, epicardium, or trachea) is identified, the operation is aborted.

The extrapleural dissection is continued until the right upper lobe and right mainstem bronchus are exposed. Resectability is assessed by direct palpation posteriorly for aortic and esophageal invasion. The esophagus is dissected away from the tumor, facilitated by palpation of the nasogastric tube to avoid injury (Fig. 122-5). The pericardium is opened anteriorly, and the pericardial space is palpated to assess for myocardial invasion (Fig. 122-6). In the absence of mediastinal extension, diaphragmatic resection is initiated.

The diaphragm is incised first at its lateral margin, followed by a circumferential resection anteriorly and posteriorly (Fig. 122-7). The diaphragmatic muscle attachments to the chest wall are cauterized or bluntly avulsed (Fig. 122-8). The peritoneum is bluntly dissected off the diaphragm (Fig. 122-9). Dissection is performed at the inferior vena cava and esophageal hiatus with caution (Fig. 122-10). The pericardial incision is extended. The junction of the pericardium and diaphragm and the medial aspect of the diaphragm are divided. With release of the diaphragmatic attachments medially and posteriorly, the esophagus is dissected away from the specimen.

The anterior pericardial incision is extended to the level of the hilum. The main right pulmonary artery is dissected intrapericardially (Fig. 122-11). A soft-flanged catheter (endoleader) is passed around the pulmonary artery to guide the safe passage of the endovascular stapler (United States Surgical, Norwalk, CT), which facilitates division of the pulmonary artery (Fig. 122-12). The superior and inferior pulmonary veins are divided intrapericardially in the same fashion. After division of the hilar vessels, the posterior pericardium is incised, completing the pericardial resection (Fig. 122-13).

The right mainstem bronchus is dissected and encircled as close to the carina as possible with a heavy-gauge wire bronchial stapler (TA-30, Ethicon, Johnson & Johnson, Cincinnati, OH) (Fig. 122-14). Before dividing the bronchus, the contralateral lung is handbag ventilated (Valsalva maneuver by anesthesia) to confirm that the contralateral bronchus is free of encroachment, and the stump is visualized under direct bronchoscopic examination to ensure a short bronchial stump. With division of the bronchus, the en bloc resection (i.e., lung, pleura, pericardium, and diaphragm) is complete, and the specimen is removed from the thorax. A frozen-section analysis of the bronchial margin is performed by pathology.