Adult Chest Surgery

Chapter 103. Extrapleural Pneumonectomy for Diffuse Malignant Pleural Mesothelioma and Other Diffuse Pleural Malignancies 

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

In the 1940s, Sarot 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 6–13%.In the 1990s, significant improvements in mortality rates were achieved. In 1999, our institution reported the lowest published operative mortality of 3.8%.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 103-1). 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) of greater than 2 L is considered adequate for pneumonectomy. Quantitative ventilation/perfusion scanning is indicated only 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 L are acceptable candidates for EPP. Patients with a predicted postoperative FEV1 of less than 0.8 L are considered for pleurectomy and decortication (see Chap. 102).

Table 103-1. Patient Selection Criteria

Karnofsky performance score


Renal function

Creatinine < 2

Liver function

AST < 80 IU/L, total bilirubin < 1.9 mg/dL, PT < 15 s

Pulmonary function

Postoperative FEV1 > 0.8 L as per PFTs and quantitative ventilation/perfusion scans

Cardiac function

Grossly normal cardiac function as per ECG and echocardiography (ejection fraction preferably >45%)

Extent of disease

Limited to ipsilateral hemithorax with no transdiaphragmatic, transpericardial, or extensive chest wall involvement


AST = aspartate aminotransferase; PT = prothrombin time, seconds; FEV1 = forced expiratory volume in 1 second; PFTs = pulmonary function tests; ECG = electrocardiography; EF = ejection fraction.

Adapted with permission from ref. 4.

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.However, chest MRI and CT scan can be unreliable in assessing chest wall invasion. As a result, exploration is offered to patients who have subtle radiographic evidence of chest wall invasion but no locally advanced or distant disease. The presence of chest wall involvement at exploration is a contraindication to resection. On the other hand, tumor with 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 abdominal invasion because of the difficulty in distinguishing local tumor compression on the diaphragm from transdiaphragmatic peritoneal invasion. Radiologic evidence of transdiaphragmatic extension, intraabdominal tumor, or ascites is an indication for exploratory laparotomy or diagnostic laparoscopy 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. The role of ultrasound-guided fine-needle aspiration or core needle biopsy is currently being evaluated. As a result, thoracoscopic pleural biopsy is recommended via a single port along the incision line of a future thoracotomy. Radiologic suggestion of contralateral thoracic disease requires pleural or lung biopsy first from the contralateral side. Staging cervical mediastinoscopy is performed. If there is metastatic disease to the mediastinal lymph nodes, the patient undergoes chemotherapy. In the absence of mediastinal involvement, the patient would proceed to surgical resection.



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 is 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 intraabdominal 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 intraabdominal disease, histologic diagnosis is confirmed by biopsy, and the resection is aborted.

In the absence of intraabdominal spread, an extended right posterolateral thoracotomy is performed (Fig. 103-1). The incision is started midway between the posterior scapular tip and the spine (inset) and extended along the sixth rib to the costochondral junction.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.

Figure 103-1.


Incision and exposure for a right posterolateral thoracotomy.


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. 103-2). At the apex, care should be taken to avoid injury to the subclavian vessels (Fig. 103-3). 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. 103-4). 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.

Figure 103-2.


Two chest retractors are placed, one anterior and one posterior, to increase the exposure.


Figure 103-3.


Care is taken to avoid the subclavian vessels while dissecting the pleura at the lung apex.


Figure 103-4.


After advancing over the apex, the pleural dissection proceeds inferiorly, with attention to the azygos vein and superior vena cava.


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. 103-5). The pericardium is opened anteriorly, and the pericardial space is palpated to assess for myocardial invasion (Fig. 103-6). In the absence of mediastinal extension, diaphragmatic resection is initiated.

Figure 103-5.


A nasogastric tube in the esophagus aids in palpating the esophagus while dissecting the pleura from the esophagus.


Figure 103-6.


The pericardium is opened anteriorly, and the pericardial space is palpated to assess for myocardial invasion.


The diaphragm is incised first at its lateral margin, followed by a circumferential resection anteriorly and posteriorly (Fig. 103-7). The diaphragmatic muscle attachments to the chest wall are cauterized or bluntly avulsed (Fig. 103-8). The peritoneum is bluntly dissected off the diaphragm (Fig. 103-9). Dissection is performed at the inferior vena cava and esophageal hiatus with caution (Fig. 103-10). 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.

Figure 103-7.


The diaphragm is incised circumferentially.


Figure 103-8.


The diaphragm is separated bluntly or by avulsion from the chest wall muscular attachments.


Figure 103-9.


The diaphragm is dissected bluntly from the underlying peritoneum.


Figure 103-10.


Dissection around the esophageal hiatus and inferior vena cava.


The anterior pericardial incision is extended to the level of the hilum. The main right pulmonary artery is dissected intrapericardially (Fig. 103-11). 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. 103-12). 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. 103-13).

Figure 103-11.


The posterior pericardium and medial aspect of the diaphragm are divided.


Figure 103-12.


An (endoleader) is passed around the pulmonary artery to guide the safe passage of the endovascular stapler, and the right pulmonary artery is divided.


Figure 103-13.


The right pulmonary artery is dissected.


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. 103-14). Before dividing the bronchus, the contralateral lung is handbag ventilated to confirm that the contralateral bronchus is free of encroachment, and the stump is visualized directly with bronchoscopy by the anesthesia team 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.

Figure 103-14.


The right mainstem bronchus is encircled as close to the carina as possible before division with a heavy-gauge wire bronchial stapler.


For complete staging, the paratracheal, subcarinal, paraesophageal, and inferior pulmonary ligament lymph nodes are resected (Fig. 103-15).

Figure 103-15.


Lymph nodes are dissected for clinical staging.


Warm saline is instilled into the chest, and handbag ventilation is performed to 30 mm Hg to check for air leaks along the bronchial staple line. Chest wall hemostasis is achieved with liberal use of the argon beam coagulator (Valleylab, Boulder, CO). Any areas of gross tumor are marked with metallic clips to facilitate adjuvant radiation therapy.

The greater omentum is mobilized off the transverse colon, and the vascular supply is contoured from a pedicle off the gastroepiploic arteries along the greater curvature of the stomach (Fig. 103-16). The omental flap is used later to buttress the bronchial stump.

Figure 103-16.


The omental flap is harvested for later use as a bronchial buttress.


The diaphragmatic and pericardial defects are reconstructed with Gore-Tex (W.L. Gore and Associates, Flagstaff, AZ). The diaphragm is reconstructed using two pieces (20 cm x 30 cm) of 2-mm-thick Gore-Tex dual mesh stapled together in a side-by-side fashion with slight overlap at the center (Fig. 103-17). The mesh is contoured to the hemithorax. This creates a loose, floppy patch at the center with less tension along the suture line. This dynamic patch is less likely to be complicated by patch dehiscence from the chest wall and abdominal content herniation into the pneumonectomy cavity. The diaphragmatic patch is sutured anteriorly, laterally, and posteriorly to the chest wall with nine Gore-Tex sutures placed through the patch and intercostal space. Each suture is passed through a 14-mm polypropylene button. The sutures are tied down on the button, buttressing the patch to the chest wall (Fig. 103-18). Before completing the diaphragm reconstruction medially, a small opening is created on the medial midportion of the diaphragmatic patch to permit the omental flap to be brought into the pneumonectomy space (Fig. 103-19). The patch is sewn medially to the pericardial edge and diaphragmatic crus.

Figure 103-17.


The diaphragmatic patch is constructed from two pieces of 2-mm-thick Gore-Tex dual mesh.


Figure 103-18.


Polypropylene buttons (14 mm) (A) are used to buttress the (B) suture that secures the patch to the chest wall.


Figure 103-19.


A small opening is made in the midportion of the diaphragmatic patch for the omental flap.


The pericardium is reconstructed to prevent cardiac herniation into an empty right hemithorax, a potentially fatal complication. A 15 cm x 20 cm, 0.1-mm-thick, Gore-Tex pericardial patch is fenestrated to prevent fluid accumulation and cardiac tamponade and is sewn to the pericardial edge with interrupted Gore-Tex sutures placed posteriorly first, followed by anterior placement (Fig. 103-20A ). Both patches are sutured to the cut edge of the pericardium and to each other medially (Fig. 103-20B ). Tension on the pericardial patch should be avoided to prevent dehiscence along the suture line.

Figure 103-20.


A. The pericardial patch is fenestrated and sewn to the pericardial edge. B. Both patches are sutured to the cut edge of the percardium and to each other medially.


After the pericardial and diaphragmatic reconstruction is completed, the omental flap is sutured to the bronchial stump to provide coverage and separation from the pulmonary artery staple line (Fig. 103-21). Alternatively, an intercostal muscle or pericardial fat pad may be used. However, we have found that the omentum provides a more reliable vascularized buttress to the bronchial stump.

Figure 103-21.


The omental flap is sutured to the bronchial stump.

The thoracotomy is closed in standard fashion. A 12F red rubber catheter is placed into the pneumonectomy space and brought out on the medial aspect of the incision. The chest wall is closed in layers. The red rubber catheter is connected to a three-way stopcock, and 1000 mL of air in men or 750 mL in women is removed, positioning the mediastinum to the midline. After the chest is closed, the patient is placed in the supine position, and flexible bronchoscopy is performed to assess the bronchial stump and clear secretions. The patient is extubated in the OR.


The technique of left EPP is similar to the technique used for the right side with some key variations.2,6,7 Important differences in the approach to anesthesia include placement of a right-sided double-lumen endotracheal tube or left-sided endobronchial blocker.

During the posterior extrapleural dissection, it is critical to enter the preaortic plane to prevent inadvertent injury of the intercostal branches. Also, caution should be exercised around the thoracic duct and recurrent laryngeal nerve during dissection in the area of the aortopulmonary window and the subclavian vessel takeoff from the aortic arch (Fig. 103-22). During the diaphragmatic resection, it is imperative to leave a 2-cm rim of diaphragmatic crus near the gastroesophageal junction (Fig. 103-23). Placement of sutures to this rim of crus during patch reconstruction prevents gastric herniation into the pneumonectomy space. Since the left main pulmonary artery is relatively shorter than the right pulmonary artery, it is divided extrapericardially (Fig. 103-24). The left mainstem bronchus should be dissected deep to the aortic arch and as close to the carina as possible. This ensures a short bronchial stump after division. After mediastinal lymph node dissection, the aortopulmonary nodes are removed as well. We routinely reconstruct the pericardial defect after left EPP to prevent constrictive epicarditis. By using the red rubber catheter, less air is removed from the left pneumonectomy space (750 mL in men and 500 mL in women).

Figure 103-22.


Exposure and vital structures at jeopardy for a left-sided EPP.


Figure 103-23.


Leave 2 cm of diaphragm around the esophagus.


Figure 103-24.


The left pulmonary artery is divided extrapericardially because it is shorter in comparison with the right pulmonary artery.


As soon as the patient is admitted to the ICU, a standard portable chest radiograph is obtained to confirm placement of the central line, identify appropriate location of the nasogastric and chest tubes, and assess mediastinal position. If a red rubber catheter was placed at surgery, the pressure measurement aids in the postoperative management and is monitored with aspiration of the pleural space, if necessary, to maintain a pleural pressure of less than 10 cm H20. This always should be correlated with the clinical picture. We recommend aspirating no more than 200–300 mL per treatment to avoid pulmonary edema or complications of acute respiratory distress syndrome. Also, additional air may be introduced or removed if the mediastinum is deviated from the midline. Patients are initially managed in the ICU for 2–3 days and then transferred to the thoracic intermediate care unit. Patients who have undergone intraoperative intracavitary heated chemotherapy (see Chap. 104) receive liberal amounts of IV fluids for the initial 24 hours to facilitate renal protection by means of hydration and to prevent hypotension. Otherwise, in patients who have not undergone intraoperative intracavitary heated chemotherapy, fluid is restricted to 1 L/day for 3–5 days. Volume requirements are met with colloids and blood transfusions preferably. The hematocrit is maintained above 30.

Prevention of pulmonary complications, namely, pulmonary embolus and aspiration, is the focus of postoperative management. A thoracic epidural is used routinely for postoperative analgesia for several days until the patient is transitioned to oral pain medications. Chest physiotherapy is encouraged daily. Deep vein thrombosis prophylaxis is achieved with subcutaneous heparin (5000 units) three times per day and pneumatic compression boots. Routine lower extremity noninvasive ultrasound is obtained every 7 days to assess for deep vein thrombosis. Patients remain at bed rest for 48 hours until midline mediastinal stability is achieved. After 48 hours, patients ambulate several times a day. Desaturations are treated aggressively with diuresis and chest physiotherapy. Bedside bronchoscopy under conscious sedation is performed with a low threshold. If pulmonary embolus is suspected, a high-resolution chest CT scan is obtained liberally.

Daily chest radiographs are obtained to assess mediastinal position and surveillance for infiltrates in the remaining lung. Any suggestion of pneumonia clinically or radiologically is treated aggressively with intravenous antibiotics, chest physiotherapy, and bronchoscopy, if indicated.

Nasogastric tubes are used to decompress the stomach and to prevent aspiration. These are removed on postoperative day 2. Oral intake is advanced slowly on resumption of bowel function. The red rubber catheter or chest tube, if placed, is removed on postoperative day 3.

Generation of a poor cough or voice change is suggestive of possible vocal cord dysfunction from recurrent laryngeal nerve injury. Prompt evaluation with direct laryngoscopy is indicated because these patients are not able to protect the airway and hence are at significant risk of aspiration. If there is vocal cord paresis or paralysis, early cord medialization is indicated for airway protection.


EPP is a technically challenging operation associated with high morbidity but acceptable mortality. Our results from the Brigham and Women's Hospital/Dana Farber Cancer Institute were reported in a paper describing 328 patients with mesothelioma who underwent EPP.The overall minor and major morbidity rate after EPP was 60.4% (198 of 328 patients) (Table 103-2). Perioperative mortality can be minimized by early detection and aggressive treatment of these complications. This approach has lowered our mortality rate to 3.4% (11 of 328 patients), and the causes of death are listed in Table 103-3.

Table 103-2. Post-EPP Morbidities (n = 328)


Median, 58 y; range, 28–77 y

Length of stay

Median, 10 d; range, 4–101 d



Minor and major morbidity rate

60.4% (198 of 328)

Atrial fibrillation

44.2% (145 of 328)

Myocardial infarction

1.5% (5 of 328)

Constrictive physiology

2.7% (9 of 328)

Reoperation for constrictive physiology

2.4% (8 of 328)


3.6% (12 of 328)

Cardiac arrest

3% (10 of 338)

Prolonged intubation

7.9% (26 of 328)


2.7% (9 of 328)

Acute respiratory distress syndrome

3.6% (12 of 328)


1.8% (6 of 328)

Vocal cord paralysis

6.7% (22 of 328)

Renal failure

2.7% (9 of 328)

Deep vein thrombosis

6.4% (21 of 328)

Pulmonary embolus

1.5% (5 of 328)

Cerebrovascular accident (33 days postoperative)

0.3% (1 of 328)


2.4% (8 of 328)

Bronchopleural fistula

0.6% (2 of 328)

Technical complications (e.g., patch failure or bleeding)

6.1% (20 of 328)

Ischemic colitis, grade II

0.3% (1 of 328)


0.9% (3 of 328)

Colectomy for Clostridium difficile

0.3% (1 of 328)


*Percentage of patients (n/total).

Adapted with permission from ref. 4.

Table 103-3. Causes of Death


No. of Patients (n = 20/496)

Pulmonary embolus


Acute respiratory distress syndrome


Myocardial infarction




Cardiac herniation


Renal failure


Cardiac arrthythmia


Heparin-induced thrombocytopenia



Adapted with permission from ref. 4.

Cardiac Complications

Atrial fibrillation was the most common cardiac and overall morbidity, occurring in 44.2% of our patients. Although numerous preventive strategies have been attempted, none has proved to be effective. Currently, we are using beta blocker medications in the postoperative period for atrial fibrillation prophylaxis.

Constrictive cardiac physiology owing to epicarditis was demonstrated by cardiac catheterization or echocardiography in 2.7% of patients. Byrne and colleagues reported seven patients who underwent a left EPP with no pericardial reconstruction and later developed constrictive cardiac physiology from a fibrous inflamed peel over the heart.These patients required reoperation and epicardiectomy. We now routinely reconstruct the left pericardial defect with a Gore-Tex patch and have not encountered further complications of constrictive physiology.

Cardiac tamponade was seen in 3.6% of patients. This can occur as a result of retained pericardial effusion from an inadequately fenestrated patch, impaired ventricular filling during diastole from a tight pericardial patch, or impingement of the inferior vena cava from a tight right-sided diaphragmatic patch. An important clue to cardiac tamponade physiology is seen in the OR when the patient becomes hypotensive with elevated central venous pressure on turning from the lateral decubitus to the supine position. The treatment is reoperation and loosening of the pericardial or diaphragmatic patch reconstruction.

Although myocardial infarction was seen only in 1.5% of patients, pericarditis as demonstrated by ST-segment elevation and elevated cardiac enzymes was common. Normalization of the electrocardiogram and cardiac markers occurred within 48 hours.

Cardiac arrest was seen in 3% of patients. This occurrence within the immediate 10-day postoperative period requires emergent reopening of the thoracotomy incision, open cardiac massage, and removal of the pericardial patch. Standard chest compression is ineffective in the EPP patient because the mediastinum is dynamic and shifts to the empty pneumonectomy space. After resuscitation, reoperation in the OR is indicated for pulsed irrigation of the opened chest and correction of the cause of cardiac arrest.

Pulmonary Complications

Pulmonary complications included prolonged intubation (7.9%), aspiration (2.7%), acute respiratory distress syndrome (3.6%), tracheostomy placement (1.8%), and vocal cord paralysis (6.7%). Unilateral vocal cord weakness or paralysis was closely related to the pulmonary complications. Extensive dissection in the aortopulmonary window and subclavian vessel takeoff from the aortic arch may result in injury to the recurrent laryngeal nerve. These patients with surgery in high-risk areas, regardless of symptoms, are evaluated with direct laryngoscopy to assess vocal cord movement in the early postoperative period. Patients with obvious symptoms of vocal cord dysfunction, such as hoarseness and poor cough, are evaluated as well. Unilateral vocal cord weakness or paralysis impairs the ability to prevent aspiration, a life-threatening complication in pneumonectomy patients. As a result, we advocate early vocal cord medialization with Gelfoam injection to reduce the incidence of aspiration pneumonia.After medialization, swallowing evaluation by speech pathology is required before resumption of oral intake.

Postoperative diuresis is important to prevent pulmonary edema. Chest physiotherapy is used aggressively with frequent ambulation. The bronchoscope is used liberally to clear secretions and during episodes of desaturation.

Excessive mediastinal shift toward the contralateral hemithorax and away from the pneumonectomy side can result in poor lung expansion and atelectasis with resulting respiratory compromise. A red rubber catheter or chest tube is left in place until the third postoperative day and is used to remove fluid from the pneumonectomy space to facilitate midline mediastinal positioning. Excessive bleeding or chylothorax may account for rapid fluid accumulation into the EPP cavity. Chylothorax occurs rarely and can be treated with percutaneous embolization or open ligation of the thoracic duct (see Chap. 113).

Renal, Hematologic, and Infectious Complications

Renal failure occurred in 2.7% of patients and in general was associated with acute respiratory distress syndrome, multi-organ-system failure, and death. Deep vein thrombosis was diagnosed in 6.4% and pulmonary embolus in 1.5% of patients. Pulmonary embolus is a life-threatening complication in pneumonectomy patients. As a result, noninvasive ultrasound of both lower extremities is obtained routinely every 7 days in the postoperative period. Furthermore, a high-resolution pulmonary embolus protocol CT scan is performed with a low threshold in patients with clinical evidence suggestive of a possible pulmonary embolus.

Empyema was seen in 2.4% of post-EPP patients, a catastrophic complication in the presence of prosthetic patches. Clinical evidence of infection is often absent, and the cultures are frequently negative, particularly for anaerobic infections. Our preventive strategy includes intraoperative pulsed irrigation of the pneumonectomy space with 9 L of lavage and a postoperative IV antibiotic regimen for 5 days with cefazolin (Ancef; Smith Kline Beecham, Philadelphia, PA), levofloxacin (Levaquin; Ortho-McNeil, Raritan, NJ), and metronidazole (Flagyl; Searle, Skokie, IL)(Fig. 103-25).

Figure 103-25.


Thoracoscopic drainage for early treatment of empyema.

Management of empyema depends on the timing of presentation relative to resection. In patients with empyema in the absence of a bronchopleural fistula during the first postoperative month, we have performed thoracoscopic closed chest treatment with debridement, pulsed irrigation, and removal of patches with success. Postoperative irrigation of the pneumonectomy space is carried out for 5 days. If the severity of the infection is deemed inappropriate for thoracoscopic management or in the presence of a bronchopleural fistula, a Clagett window is performed, with the Gore-Tex patches left in place. Staged removal of the patches may prevent mediastinal shift into the pneumonectomy cavity. After 2–3 weeks of dressing changes and adequate time for the mediastinum to scar into place, the patches are removed. Patients who present with empyema months to years after resection are managed traditionally with a Clagett window and open patch removal at the same time.

Bronchopleural fistula has occurred in 0.6% of patients. The presence of a bronchopleural fistula requires Clagett window drainage of the pneumonectomy cavity and patch removal.


The success of EPP in the treatment of mesothelioma has been attributed to defined criteria for patient selection, continuous refinements in technique, and a disciplined approach to the perioperative care with early diagnosis and aggressive treatment of complications. This is exemplified by the reduction in postoperative mortality and improvement in survival.

Our report from the Brigham and Women's Hospital of 183 patients who underwent EPP followed by adjuvant chemotherapy and radiation for mesothelioma revealed an overall median survival of 19 months, with 2- and 5-year survivals of 38% and 15%, respectively(Fig. 103-26). The revised Brigham and Women's Hospital staging system for malignant pleural mesothelioma was applied to this cohort of patients (Table 103-4). The staging system had prognostic significance because it significantly stratified long-term survival. Patients with stage I (n = 66), II (n = 41), and III (n = 69) disease had median survival intervals of 25, 20, and 16 months, respectively.A subset of 31 patients with epithelial cell type, negative resection margins, and negative extrapleural nodal status had a median survival of 51 months, with 2- and 5-year survivals of 68% and 46%, respectively(Fig. 103-27).

Figure 103-26.


Kaplan-Meier survival curve for all patients surviving surgery (n = 176). (Reproduced with permission from Sugarbaker DJ, Flores RM, Jaklitsch MT, et al: Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: Results in 183 patients. J Thorac Cardiovasc Surg 117:54–63.)


Table 103-4. The Revised Brigham Staging System for Malignant Pleural Mesothelioma




Disease confined to within the capsule of the parietal pleura; ipsilateral pleura, lung, pericardium, diaphragm, or chest wall disease limited to previous biopsy sites


All of stage I with positive intrathoracic (N1 or N2) lymph nodes


Local extension of disease into chest wall or mediastinum; heart, or through the diaphragm and peritoneum; with or without extrathoracic or contralateral (N1) lymph node involvement


Distant metastatic disease


Adapted with permission from ref. 3.

Figure 103-27.


Kaplan-Meier survival curves for patients with epithelial subtype. (Reproduced with permission from Sugarbaker DJ, Flores RM, Jaklitsch MT, et al: Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: Results in 183 patients. J Thorac Cardiovasc Surg 117:54–63.)


In the last 20 years, the EPP technique has been modified with the incorporation of novel surgical techniques that have led to improved survival, reduced operative time, and a steady reduction in postoperative mortality. The described technique is the culmination of 20 years' experience with malignant pleural mesothelioma at the Brigham and Women's Hospital/Dana Farber Cancer Institute. The successful refinement of the operation, as demonstrated by the current low mortality rate, has allowed application of the procedure to treat other malignancies, such as locally advanced lung cancer and thymoma. The basic stages of this operation are (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 This is a complex and challenging procedure, as exemplified by an overall morbidity rate of 60.4%.This operation should be performed only by an experienced surgical team at a high-volume, experienced medical center.10 The associated complications require a unique management approach with early detection and aggressive treatment in order to achieve a mortality rate of 3.4%.4


A 58-year-old former shipyard worker presented with a several-month history of progressive shortness of breath, nonproductive cough, and 10-lb weight loss. His past medical history was unremarkable except for previous asbestos exposure. The physical examination was remarkable for right-sided decreased breath sounds, dullness to percussion, decreased tactile fremitus, and egophony. A chest x-ray revealed a moderate-sized right pleural effusion, pleural thickening, shrinkage of the ipsilateral hemithorax, and shift of the mediastinum to the right chest. A chest CT scan was obtained that confirmed the chest x-ray findings and also demonstrated diffuse pleural thickening encasing the right lung with questionable chest wall invasion along the sixth and seventh ribs laterally. Chest MRI showed no diaphragmatic or mediastinal invasion.

Right thoracoscopic drainage of the pleural effusion and pleural biopsy were performed, which revealed no malignant cells on cytology and epithelial mesothelioma on histologic examination. Cervical mediastinoscopy with mediastinal lymph node biopsy demonstrated no evidence of metastatic spread.

Standard laboratory tests, including liver function tests, creatinine, and arterial blood gases, were normal. Pulmonary function testing revealed an FEV1 of 1.8 L. Ventilation/perfusion scan was performed, which showed lung perfusion to the right lung at 10% and to the left lung at 90%. The predicted postoperative FEV1 was calculated to be 1.6 L. Echocardiogram demonstrated no evidence of pulmonary hypertension (20 mm Hg plus right atrial pressure) and normal ejection fraction (60%), valvular function, and wall motion.

In the absence of locally advanced or distant disease with a confirmed histologic diagnosis of mesothelioma, an extended right thoracotomy was performed. There was no intraoperative evidence of chest wall invasion because the extrapleural plane was dissected readily. As a result, we proceeded to perform a complete EPP, as described earlier. At the end of the operation, 1000 mL of air was removed via the red rubber catheter. Bronchoscopy revealed a short bronchial stump and retained secretions, which were suctioned. The patient was extubated in the OR and transferred to the ICU. Postoperative chest x-ray revealed that the mediastinum was shifted to the left hemithorax. An additional 400 mL of air was removed via the red rubber catheter, and repeat chest x-ray revealed the mediastinum in the midline position.

On postoperative day 1, the patient was noted to have a hoarse voice. An urgent otolaryngology consult was obtained, and direct laryngoscopy was performed at the bedside, which revealed a paralyzed right vocal cord. The patient was restricted from oral intake and underwent vocal cord medialization with Gelfoam injection the next day. There was significant improvement in his voice thereafter. The nasogastric tube was removed on postoperative day 2, and speech pathology evaluation revealed normal swallowing. The patient was started on an oral diet. Fluid intake was restricted to 1 L/day, and gentle diuresis was initiated.

On postoperative day 3, the red rubber catheter was removed after confirming on a routine daily chest x-ray that the mediastinum was midline in location. The patient was transferred to the stepdown thoracic intensive care unit. Aggressive chest physiotherapy was performed frequently, and the patient ambulated four times a day. On postoperative day 7, the patient underwent routine noninvasive ultrasound of the lower extremities, which revealed no evidence of deep vein thrombosis. On postoperative day 10, the patient was discharged to home with continued improvement. At 7 days from discharge, he was seen in clinic and was noted be doing well. The final pathology report revealed epithelial mesothelioma in the EPP specimen, and extrapleural lymph nodes revealed no evidence of malignancy. He successfully underwent adjuvant chemotherapy and radiation.


Despite major reductions in operative mortality over the last 30 years, extrapleural pneumonectomy remains a technical tour de force intraoperatively and requires intensive postoperative management as well. Such operations should be attempted in centers that treat large numbers of patients. Early detection of complications is crucial to limit their physiologic impact on this tenuous group of patients.



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