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Extrapleural pneumonectomy

Yifan Zheng, William G. Richards, Julianne S. Barlow, Adrienne Camp and Raphael Bueno

HISTORY

The incidence of malignant pleural mesothelioma (MPM) worldwide is expected to increase in the next two decades. ¹ The paradigm for treatment of this aggressive disease has evolved to include combined multimodality therapies, which offer the prospect of improved outcomes for selected patients with clinically localized disease. ²

The extrapleural pneumonectomy (EPP) operation consists of the en bloc resection of parietal pleura, lung, ipsilateral pericardium, and hemidiaphragm, and the subsequent reconstruction of the defects left from the excised pericardium and diaphragm. This operation was first described in the 1940s for an infectious empyema ³ and is now used to treat some malignancies such as MPM, as well as, on occasion, destroyed lung from chronic infections. As part of a multimodality treatment regimen, this operation is performed with curative intent in carefully selected MPM patients. A less extensive resection, known as “pleurectomy and decortication” (PDC) is preferred for patients who have earlier stage disease. PDC, extended PDC, or partial pleurectomy may be performed and is often reserved for patients who have disease confined to one hemithorax but are unable to tolerate an EPP. ⁴

PRINCIPLES AND JUSTIFICATION

The initial EPPs performed in patients with MPM in the 1970s and 1980s were associated with mortality rates as high as 30%-40%. ⁵ As a consequence, most surgeons either preferred to perform what they thought was a less aggressive operation—pleurectomy or partial pleurectomy—usually as a palliative approach to relieve dyspnea, or, more likely, avoided surgery altogether. However, persistent focus on improving the surgical outcome at a small number of specialized institutions in the early 1990s resurrected this procedure and established new patient-selection strategies, decreased operative times, improved surgical techniques, and focused preand postoperative management regimens, resulting in reducing mortality to as low as 3.4%-5.2%. ⁶ , ⁷ This initial success has led to additional institutions progressively developing surgical programs for MPM and wider acceptance of this approach in the medical community. Though morbidity rates remain high, ranging from 38% to 59%, the range of mortality rates dropped substantially to 3% from 12% as surgeons gained more experience with the procedure and especially with managing early postoperative complications. ^{8 − 13}

PREOPERATIVE EVALUATION AND PATIENT SELECTION

Successful application of multimodality treatment approaches depends critically on patient selection. Through the collective experiences of specialty centers for this rare disease, a standardized staging system for surgical patients has been established and continues to evolve. ¹⁴ In addition, because clinical staging of MPM is challenging for a variety of reasons, a number of predictive clinical and molecular biomarkers have been established to assist with selecting appropriate MPM patients for surgery. These include histology, lymph node status (negative better than positive), hemoglobin, sex >, tumor volume, and the gene ratio prognostic molecular test. ⁷ , ^{15 − 19}

Patients with MPM often present with nonspecific symptoms such as chest pain and shortness of breath. Evaluation begins with a thorough history and physical, noting risk factors such as asbestos exposure and smoking history. Imaging evaluation includes chest computed tomography and magnetic resonance imaging (MRI) to evaluate the extent of disease invasion. MRI is particularly helpful in determining diaphragmatic or great vessel involvement. If there is extensive invasion into the chest wall, abdominal cavity, mediastinum, or contralateral hemithorax, radical resection is contraindicated. Imaging may show pleural effusion or pleural nodularity. Cytologic diagnosis may be obtained from sampling the pleural fluid but is often inconclusive. Instead, histologic diagnosis by thoracoscopic pleural biopsy is recommended to establish a definitive diagnosis, since differentiating adenocarcinoma from mesothelioma may, at times, be challenging. As the extent of invasive disease is not always apparent on imaging, thoracoscopic and laparoscopic exploration allows for direct evaluation of disease spread and is recommended to patients if there are radiologic concerns for chest wall or diaphragmatic invasion. ²⁰ A single thoracoscopic incision should be made in the line of a future thoracotomy. Partial pleurectomy or insufflation of talc at the time of diagnosis is discouraged. Additionally, a staging cervical mediastinoscopy is performed, and if the findings are negative—that is, no metastatic disease found in the lymph nodes—the preparation continues for an EPP.

Once a pathological diagnosis is established, a diagnosis of the histological subtype must also be rendered. The epithelioid subtype of MPM is more common and is associated with better prognosis than biphasic subtypes (mixed), while the sarcomatoid subtype has the worst prognosis. ⁷ The decision to perform an EPP should be weighed carefully and this operation should be recommended to patients with the best chances for survival, so that the associated risks are justified. However, while diagnosis by pleural biopsy is reliable, it is not always accurate for differentiating subtypes, particularly when the final pathology is nonepithelial. ²¹

As diagnosis and extent of disease are determined, the ability of the patient to tolerate pneumonectomy is evaluated. The following selection criteria are based on the experience of Brigham and Women’s Hospital, which has reached an annual volume of 90 to 100 major surgical resections for MPM including approximately 30 to 50 EPPs. To be eligible for an EPP, a patient must have good performance status, usually indicated by a Karnofsky score of greater than 70. The patient must also have normal cardiac, liver, and renal function. This preoperative evaluation is critical to the patient’s tolerance of the operation, as well as the ability to tolerate hyperthermic intraoperative chemotherapy should operation be offered. ²² A pulmonary function test is obtained usually in conjunction with a quantitative ventilation/perfusion scan to ensure that patients meet the minimum criteria of 1 L of predicted postoperative FEV₁ and favorable distribution of perfusion.

Each patient being considered for an EPP has a Doppler echocardiogram to evaluate for pulmonary hypertension and further evaluation is obtained as warranted by the results and age of the patient. Usually, an exercise stress test or echocardiogram is also advised. When there is a question as to operability based on findings of cardiac disease or pulmonary hypertension, catheterization and/or a pulmonary exercise test for determination of mixed venous oxygen saturation is obtained. Pulmonary hypertension is a concerning contraindication to proceeding with an EPP.

As the recommendation for an EPP is based on the performance status of the patient and the extent of disease, there is no absolute age restriction for undergoing the operation. However, the surgery is rarely recommended to patients older than 70 years of age, particularly when considering the morbidity and mortality risks. In fact, age over 70 to 75 years is an independent risk factor for mortality after EPP. One should also consider that a left-sided EPP is better tolerated than one done for right-sided disease and some criteria may be relaxed for left-sided MPM.

Preoperatively, patients are treated with a bowel preparation and undergo lower extremity ultrasonography to assess for deep venous thromboses.

OPERATION

Prior to beginning the operation, a thoracic epidural catheter is placed for optimal pain control. Central venous access is obtained, a pulmonary artery catheter is placed, an arterial line is established, and a Foley catheter is inserted into the bladder. Standard monitoring also includes telemetry and pulse oximetry. Antibiotic prophylaxis is administered and pneumatic compression boots are placed to guard against venous stasis of the lower extremities. General anesthesia is then induced and the patient is intubated with a single lumen endotracheal tube and fiber-optic bronchoscopy is performed to examine the airway. If no abnormalities are found, the single lumen endotracheal tube is replaced with a double lumen endotracheal tube or a selected balloon bronchial blocker is placed in the main bronchus of the operative side. A nasogastric tube is also placed for identification of the esophagus during dissection and for postoperative decompression of the stomach. Finally, the patient is repositioned as appropriate for the side of surgery in a lateral decubitus position.

Right extrapleural pneumonectomy ²⁰

1. The patient is positioned in a left lateral decubitus position and the right chest is prepared and draped in a sterile fashion. An extended right posterolateral thoracotomy is made along the sixth rib. Electrocautery is used to divide through the subcutaneous tissue and the serratus anterior and latissimus dorsi muscles. Next, the sixth rib is identified, the periosteum stripped, and the rib is resected in a subperiosteal fashion with a bone cutter, from the level of the anterior chondrocostal cartilage to that of the spinous muscles. (See Figure 14.1.)
   
2. Extrapleural dissection is begun with blunt manual dissection, establishing a plane along the anterolateral thoracic wall and proceeding toward the apex. Care should be paid to avoid injuring the subclavian vessels, and packing sponges can be placed to control bleeding from the chest wall as the dissection progresses. The trick is to keep the lung initially inflated, particularly in patients with early disease, to avoid getting into the pleural space. Then, work should continue in all directions from the incision to enlarge the extrapleural plane and concentration be put on developing long fronts of dissection. Once the entire area of incision is cleared from the chest wall, retractors are then placed anteriorly and posteriorly and the extrapleural dissection is continued. The apex is released and dissected down to the hilum from both anterior and posterior approaches. The dissection then continues medially to mobilize the lung and tumor away from the superior mediastinum, being careful not to injure the superior vena cava or azygos vein. The dissection proceeds posteriorly and it is important to remember that, just anterior to the vertebral bodies, the posterior dissection needs to move to a more shallow plane to leave the azygos vein and its branches intact The same approach applies anteriorly to spare the internal mammary arteries as the dissection nears the pericardium. (See Figure 14.2 .)
   
3. Continue the dissection inferiorly toward the lateral attachments of the diaphragm to the chest wall. This part of the dissection is performed with the surgeon’s fingertips. It is easy to feel the cleavage plane between the tumor, the diaphragm, and the peritoneum, which should stay intact. If any opening is made in the peritoneum, it should be closed primarily. Once the lateral attachments of the diaphragm are freed, one can use a sponge stick to dissect the peritoneum away, extending this dissection along the inferior vena cava. The diaphragm is also freed from its medial and pericardial attachments, leaving the crus intact for diaphragmatic reconstruction. (See Figure 14.3 .)
   
4. The pericardium is opened anteriorly and the pericardial space is evaluated for disease invasion. If any disease is detected here, elsewhere in the mediastinum, or into the chest wall, the EPP operation is aborted. The pericardial incision is made in line with the diaphragm posteriorly, allowing the identification and preservation of the inferior vena cava. There is a plane between the pericardium and the diaphragm that is extrapleural, which allows for safer dissection. The pericardium is then dissected and cut to the level of the pulmonary veins. (See Figure 14.4 .)
   
5. The separation of the EPP specimen in the same dissection plane then continues posteriorly. The nasogastric tube placed by anesthesia at the start of the operation is now palpated to help identify the esophagus, and the EPP specimen is dissected away from the esophagus to the level of the pericardium and this allows cutting the pericardium all the way to the level of the inferior pulmonary vein. Anteriorly, the pericardial incision is made at least to the level of the superior pulmonary vein, if not higher, so both veins are easily exposed for division with a stapler.
   
6. The pulmonary artery is divided (once the pulmonary artery catheter is pulled back) intrapericardially or extrapericardially, depending on the anatomy, with an endovascular stapler, and subsequently, the superior and inferior pulmonary veins are also divided in a similar manner. The mainstem bronchus is circumferentially dissected as close to the carina as possible, TA closed with a surgical stapler under bronchoscopic observation and divided. The en bloc resected specimen is sent to the pathology laboratory for analysis, which will confirm whether the bronchial stump margin of the resected specimen is negative for tumor.
   
7. Next, a lymphadenectomy is completed from regional levels 4, 7, 8, 9, and 10. Meticulous hemostasis is achieved with electrocautery or the argon beam coagulator. The hemithoracic cavity is filled with warm saline and the airway pressure is increased to 30 mmHg while the saline pool is observed for evidence of air bubbles indicating a leak in the closure of the bronchial stump. If possible, the stump should be buttressed with muscle or omentum at the conclusion of the case. It is at this point in the procedure that intraoperative heated chemotherapy is administered if the patient is an appropriate candidate. This is beyond the scope of this chapter; for more information on this treatment, see Sugarbaker et al. ²² Prior to the chemotherapy, we generally perform a manual scrub with hydrogen peroxide and then several liters of pulse irrigation using saline and water. Argon coagulation is then used to aid in hemostasis and the destruction of possible remaining tumor cells. After ensuring coagulation of all bleeding sites and removal of all macroscopic tumor, areas that may require radiation therapy are marked with clips. (See Figure 14.5 .)
   
8. The reconstruction portion of the operation consists of recreating the excised pericardium and diaphragm specifically to prevent the liver and the heart from herniating and causing hemodynamic problems. The diaphragm is reconstructed with a 1-2 mm Gore-Tex Soft Tissue Patch (W. L. Gore and Associates, Inc., Newark, Delaware, United States) secured to the chest wall and the mediastinum with interrupted Prolene sutures (Ethicon U.S., LLC, Somerville, New Jersey, United States). Medially, the patch is secured to the pericardium and the crural fibers of the diaphragm. (See Figure 14.6 .)
   
9. The pericardial defect is repaired with a 0.1 mm GoreTex patch to prevent herniation of the heart. This patch is sutured to the pericardial and diaphragmatic edges with interrupted 2-0 Prolene stitches (approximately eight) taking care to avoid making it too tight. The pericardial patch is fenestrated to allow drainage of fluid and to prevent cardiac tamponade. Care must be given not to narrow the vena-caval exit and to have no tied suture in contact with the heart lest it erode into a coronary artery. (See Figure 14.7 .)
   
10. A final check is made for hemostasis and the chest cavity is irrigated with saline. Considerations may be given to place a fat, muscle or pericardial flap to cover the bronchial stump. A 12 Fr Rob-Nel red rubber catheter (Covidien, Medtronic, Dublin, Ireland, and Fridley, Minnesota, United States) is then placed percutaneously into the operative hemithorax. The ribs are reapproximated and closed with braided absorbable sutures and the incision is irrigated. The muscles and subcutaneous tissues are reapproximated with absorbable sutures in the standard fashion, and the skin is closed with a subcuticular suture. Prior sites of access for diagnostic biopsies are resected down to muscle and closed. Dressings are applied and the patient is returned to a supine position. A three-way stopcock is connected to the red rubber catheter and 750-1000 mL of air is evacuated from the chest to help maintain the mediastinal structures in a midline position. ²³ In the intensive care unit (ICU) this catheter is used for pressure monitoring. A 24 Fr Blake drain (Ethicon U.S., LLC) is placed percutaneously into the contralateral side to help equalize the intrathoracic pressure and a completion bronchoscopy is performed as a final evaluation of the bronchial stump. The patient is then awoken from anesthesia, extubated, and taken to recovery in the ICU. (See Figure 14.8 .)

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