Timothy E. Miller
1. In an extrapleural pneumonectomy the lung is removed en bloc, together with parietal and visceral pleura, ipsilateral hemidiaphragm and pericardium, as well as mediastinal lymph nodes.
2. The operation is now reserved almost exclusively for the treatment of mesothelioma. A recent randomized control trial showed no improved survival in patients treated with surgery in the context of trimodal therapy.
3. 2-10% of individuals with prolonged asbestos exposure will develop mesothelioma, but more than 80% of mesothelioma patients have a history of exposure to asbestos.
4. The major anesthetic issues are significant blood loss, hemodynamic instability, difficult fluid therapy, risk of cardiac herniation and high probability of dysrhythmias.
The patient is a 57-year-old ex-shipyard worker who presents for an extrapleural pneumonectomy after a work-up for dyspnea revealed a malignant pleural effusion positive for mesothelioma. He has no evidence of extrathoracic disease. He has a history of 40 pack-years of smoking but has not smoked in 10 years.
He has no other medical problems and medications include only a multivitamin. Vital signs: BP 135/70, HR 70, room air SpO2 93%. Routine laboratory examination is unremarkable. Pulmonary function tests are notable for a FEV1/FVC ratio of 80%, an FEV1 of 70% predicted, a FVC of 75% predicted, and a DLCO of 50% predicted.
Extrapleural pneumonectomy (EPP) was introduced in the 1940s for the treatment of tuberculous empyema and other pleural space infections.1 It is a radical surgery that differs from conventional pneumonectomy in that the lung is removed en bloc, together with parietal and visceral pleura, ipsilateral hemidiaphragm and pericardium, as well as mediastinal lymph nodes. In modern times the operation is reserved almost exclusively for the treatment of malignant pleural mesothelioma (MPM). Rarely, it can also be performed for locally advanced lung cancer, or other malignancies and infections confined to a single pleural space.
EPP is a technically difficult operation accompanied by a significant mortality rate, recently estimated at between 3% and 7%.2-4 This has dramatically improved since the 1970s when mortality was over 30%,5 with the trend now toward improved operative survival, especially if used as part of a multimodal approach (Table 14–1). Nevertheless, morbidity remains high even in large volume centers with aggressive intervention, exceeding that for pneumonectomy.4 Accordingly its use remains controversial, and patient selection is imperative. Anesthesia management is challenging and may contribute to safe patient outcomes.
Table 14–1. Mortality of Extrapleural Pneumonectomy
MALIGNANT PLEURAL MESOTHELIOMA
Malignant pleural mesothelioma (MPM) is a rare, locally aggressive tumor of the mesothelial cells that line the pleura. It tends to spread or recur locally, and encases and invades the lung parenchyma in late stages of the disease. MPM is almost universally caused by, and in fact owes its entire existence as a disease entity to its relationship with asbestos. Asbestos is a naturally occurring mineral found all over the world but mainly in Canada, South Africa, Australia, and northern Italy. Due to its extraordinary fire-resistant properties it was used in the construction and shipping industries in the 1940s, during which time an estimated 40% of the US workforce were exposed.6 The first description of an association between MPM and asbestos exposure was by Wagner in patients exposed to the long, fine asbestos fiber crocidolite in South African mines.7 All types of asbestos fiber can cause mesothelioma, with crocidolite considered the highest risk. When inhaled, the fibers are too large to be removed by pulmonary macrophages, and over the years they burrow into the serosal surfaces of the pleura, pericardium, and peritoneum. Fortunately only 2% to 10% of individuals with prolonged asbestos exposure will develop MPM, whereas over 80% of MPM patients have a history of exposure to asbestos.8
The average latency period following exposure and development of the disease or death is very long—usually a minimum of 20 years—although the range is wide. Cases developing within 15 years of exposure are rare. This is unlike most risk factors, including smoking, when increasing time from stopping exposure to the carcinogen will decrease the risk of malignancy. In 1972, the US Occupational Safety and Health Administration established permissible exposure limits to asbestos, and since then many countries have banned its use completely. The importance and relevance of the latency period is reflected by the increasing incidence of mesothelioma. In the US the current incidence is 3000 cases per year, comprising about 3% of cancer diagnoses, and this is projected to increase until at least 2020.9
Typically, patients with MPM present with a pleural effusion, which is often associated with chest wall pain or breathlessness. The chest pain typically progresses relentlessly during the course of the illness. Constitutional symptoms such as weight loss and fatigue can be present, and are often associated with a poor prognosis. Occasionally the disease is found incidentally on a chest x-ray (Figure 14–1). CT scans often demonstrate encasement of the lung by a thickened pleural peel (Figure 14–2).
Figure 14–1. Chest radiograph demonstrating the four classic findings of a patient with the clinical diagnosis of pleural mesothelioma: pleural thickening, pleural effusion, decreased thoracic volume, and no shift of the mediastinum to the affected side.
Figure 14–2. Pleural thickening in a 51-year-old man with MPM. Axial contrast-enhanced CT scan shows circumferential and nodular left-sided pleural thickening (arrows). The tumor encases the contracted left hemithorax, having a rind-like appearance.
Diagnosis of MPM is possible from cytological examination of pleural fluid, but findings are often negative despite repeated sampling. The gold standard is thoracoscopy, which yields a diagnosis in 98% of patients.10
Without treatment, MPM is associated with an extremely poor prognosis: a median survival duration of less than 1 year and a 5-year survival rate of less than or equal to 1%.11 No single treatment modality dramatically improves this since none reliably results in cure.
The goal of any surgical treatment is complete resection. However, in the case of MPM this is rarely achieved—presumably due to the diffuse spread of MPM throughout the hemithorax, and the difficulty of achieving deep margins. Therefore, treatment has focused on surgery in combination with a multimodality treatment program. Other therapies include systemic or intrapleural chemotherapy, high-dose hemithoracic radiation, and intensity-modulated radiation therapy (IMRT).12
The two main surgical options are EPP and pleurectomy/decortication (P/D), which involves resection of the pleura, pericardium and diaphragm when necessary but spares the lung. There are no randomized controlled trials between these techniques, and no established practice guidelines. EPP offers the most complete cytoreduction, and is considered by many to be the best surgical option. However, a recent multicenter retrospective series showed improved 5-year survival after P/D.13 Previous series have argued against this perspective,14-16 with Sugarbaker et al finding a median survival of 51 months in selected patients after EPP.15 The decision to perform P/D is often made intraoperatively, with early disease commonly resected by P/D when it appears macroscopic complete resection can be achieved. Bulky disease is more likely to be approached by EPP, offering significant bias to any comparative retrospective series. An additional benefit of EPP is that it facilitates the administration of postoperative hemithoracic radiation, which is not possible after P/D, and provides excellent local disease control.17
The recent mesothelioma and radical surgery (MARS) trial is the first randomized controlled trial to compare EPP versus no EPP in the context of trimodal therapy (chemotherapy, radiotherapy, and further surgery if needed). Although the trial was small with only 50 patients randomized, patients undergoing EPP had shorter median survival (14.4 months vs 19.5 months), and more serious adverse events (10 vs 2), without any gain in quality of life. The authors therefore conclude that EPP within trimodal therapy may offer no benefit, and possibly harm patients. This is almost certain to significantly decrease the number of EPPs performed in the coming years. Further studies are needed to evaluate the role of lung sparing surgery in the future management of mesothelioma.18
TECHNIQUE OF EXTRAPLEURAL PNEUMONECTOMY
Step One: Incision
The extrapleural space is usually approached through an extended posterolateral thoracotomy incision in the sixth intercostal space with resection of the sixth rib, although a median sternotomy can be used for a right EPP.
Step Two: Extrapleural Dissection
Combined blunt and sharp extrapleural dissection is performed superiorly toward the apex of the thorax, and then medially down to the azygos vein. Packing the dissected area diminishes blood loss from the numerous small vessels lining the inner thoracic cavity. During this dissection, any internal mammary grafts on the operative side will almost certainly be lost, and there may be traction to the superior vena cava (SVC). Inferiorly the diaphragm is divided and dissected from the underlying peritoneum, taking care to keep the peritoneum intact and prevent peritoneal seeding.
Step Three: Division of the Major Vessels and Bronchus
The pericardium is opened and resected, with the major vessels dissected free. The main pulmonary artery and veins are divided using a vascular stapler. After a complete subcarinal lymph node dissection the main stem bronchus is exposed and divided (Figure 14–3). This can be performed under direct vision with a fiberoptic bronchoscope to assure a short stump that is flush with the carina.19 The specimen is then removed en bloc, followed by radical mediastinal lymph node dissection.
Figure 14–3. A. The intrapericardial dissection and isolation of the hilar vessels with subsequent ligation and division of the vessels using endoscopic vascular staplers. B. Operative drawing after completion of the pericardial and diaphragmatic reconstruction. The right bronchial stump has been reinforced with a thymic fat pad. The pericardial patch is fenestrated to prevent tamponade.
Step Four: Reconstruction
The bronchial stump is reinforced with a tissue flap, usually from either pericardial fat or a thymic fat pad. The hemithorax is then irrigated with warm saline and water to remove residual microscopic tumor. The pericardium and diaphragm are then reconstructed using Gore-Tex patches (Gore-Tex, Inc., Flagstaff, AZ) to prevent any subsequent herniation of the heart or abdominal contents into the empty hemithorax. The pericardial patch must be fenestrated to prevent any constrictive physiology occurring postoperatively. The chest is then closed in the usual fashion once hemostasis has been achieved.
Estimates have suggested that only 1% to 5% of all patients with mesothelioma might be suitable for surgery.20 Selection of appropriate patients for EPP is crucial, and varies between different centers although the principles remain the same. Table 14–2 lists commonly used patient selection criteria.
Table 14-2. Suggested Selection Criteria for Extrapleural Pneumonectomy
Importantly for a patient to be considered for an EPP, they should have a good performance status. This is defined as Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (Table 14–3).21 Patients should have adequate pulmonary function to tolerate a pneumonectomy, with predictive forced expiratory volume in 1 second (FEV1) greater than 1 liter. All patients with predictive FEV1 less than 2 liters are recommended to undergo radionucleotide ventilation-perfusion scanning to assess the contribution of the diseased lung, and improve the accuracy of the predicted postoperative value. Arterial blood gases are obtained to rule out baseline hypoxia and/or hypercapnia.
Table 14-3. Eastern Cooperative Oncology Group (ECOG) Performance Status
Two-dimensional dobutamine echocardiography is necessary to rule out ventricular dysfunction (EF <45%), significant coronary artery disease, and pulmonary hypertension (mean pulmonaryartery pressure >30 mm Hg) that may increase perioperative risks.
Patients potentially suitable for radical surgery have epithelioid tumors of low volume. Studies have consistently demonstrated the significance of epithelial histology in the outcomes of mesothelioma patients.22 The International Mesothelioma Interest Group (IMIG) developed a new staging system in 1994 based on the TNM system of lung cancer.23 Stages I and II disease are both N0M0, meaning there is no evidence of regional lymph node or distant metastases respectively. Accurate preoperative staging requires CT, MRI, PET, and often thoracoscopy and mediastinoscopy. Final staging is only possible at surgery.
Anesthesia for EPP is challenging with a high rate of perioperative morbidity. There are a number of potential management problems in addition to the standard anesthetic issues for a pneumonectomy. The major additional anesthetic issues are listed in Table 14–4.
Table 14–4. Major Anesthetic Issues for Extrapleural Pneumonectomy
Most importantly EPP is associated with significant extra blood loss as small blood vessels are disrupted during the blunt dissection of the pleura. There is also the potential for acute blood loss if major blood vessels are disrupted. This can be accompanied by alterations in preload and cardiac output caused by surgical pressure on the pericardium and great vessels. Therefore, the anesthetic plan needs to be tailored to expect hemodynamic instability and major fluid shifts.
Planning—Lines, Monitors, and Equipment
Adequate venous access is essential in these patients. If large-bore peripheral intravenous access cannot be obtained, it is prudent to insert a wide-bore central line for rapid infusion of blood products. Invasive arterial and central venous monitoring are routine. A method of delivering blood products rapidly should be available, and blood should be in the operating room. Pulmonary artery catheters are rarely used, and the data have been shown to be difficult to interpret during pneumonectomy.24 Transesophageal echocardiography (TEE) should be available to assess right and left ventricular filling and function if needed. Vasoconstricting agents should be available, especially for large tumors and if epidural anesthesia is to be used intraoperatively. It is essential that patients are adequately warmed, so appropriate use of warming devices and fluid warmers is recommended.
Thoracic Epidural Anesthesia
Thoracic epidural anesthesia (TEA) is generally considered the technique of choice for postoperative analgesia after EPP. TEA has a number of potential benefits after thoracic surgery. In a meta-analysis, compared with systemic opioids, TEA was found to decrease the overall incidence of atelectasis, pulmonary infections, and pulmonary complications in thoracic surgery.25 There are also clear benefits in areas such as pain relief, facilitation of early extubation, and reducing the length of intensive care stay. The superior pain relief is important for effective cough, vigorous physiotherapy, and mobilization in the early postoperative period. This control of postoperative acute pain is important to reduce the incidence of chronic postthoracotomy pain syndrome (see also Chapter 24).26
In EPP, the large incision makes the use of TEA even more appealing. However, the sympatholytic effects of epidural local anesthetic may complicate hemodynamic effects during the dissection phase of the operation. Consideration should therefore be given to giving an opioid bolus in the epidural space at induction, and then starting a local anesthetic and opioid infusion once the major dissection has been completed, and the risk of major bleeding has diminished.
There is no evidence that any particular anesthetic technique is superior for EPP. However, it seems sensible to use short-acting agents, and to limit intravenous narcotic use as much as possible to facilitate early extubation. An arterial line should be placed before induction to enable continuous monitoring of blood pressure, particularly in patients with a large tumor burden, and possible impairment of venous return. Induction agents should be used cautiously, often with concomitant administration of vasoconstrictors.
Lung isolation is generally best obtained by intubating the nonoperative bronchus with an appropriately sized double-lumen endotracheal tube (DLT). A left-sided DLT is an alternative for left EPP but it must be pulled back at the time of bronchial cross-clamping, thereby inevitably causing some risk of disruption to the bronchial stump. For this reason most thoracic anesthesiologists place a right-sided DLT (see Chapter 5) for a left pneumonectomy procedure. Bronchial blockers can be used but are more difficult to place, more likely to become dislodged, and there is no ability to oxygenate or suction the operative lung. Whatever technique is used, complete collapse of the operative lung does not usually occur, despite good tube position, due to pleural adhesions caused by the tumor.
Patients undergoing thoracotomy are at risk of gastroesophageal reflux (GER), which may lead to tracheal aspiration in an appreciable proportion of patients. Therefore, prophylactic pharmacologic management of GER should be given preoperatively.27 The DLT should be positioned with a fiberoptic bronchoscope to prevent the need for repositioning and cuff deflation, and gel lubrication should be applied to the DLT cuff to prevent aspiration past microfolds in the inflated cuff when it comes into contact with the trachea.28
During one-lung ventilation (OLV), a protective ventilation strategy should be used to prevent volutrauma, barotrauma, and atelectrauma (low-volume injury). Lung protective strategies include a 3 to 4 mL/kg tidal volume, minimizing PEEP (and a high index of suspicion for auto PEEP), and limiting plateau and peak inspiratory pressures to less than 25 cm H2O and 35 cm H2O, respectively. The weight of the tumor in EPP can inhibit compliance of the dependent lung, and mechanical pressure causing changes in compliance require vigilance to prevent high airway pressures or volumes.
During the dissection phase of EPP, hemodynamic management is frequently difficult and complex. Hypotension is common and multifactorial, with disruption of venous return, blood loss, and mechanical pressure on the pericardium and great vessels all contributing. Blood loss during EPP is nearly always at least 1 L and can be significantly more even in experienced hands. Communication with the surgical team is vital to limit changes in hemodynamics whilst proceeding with the dissection. Brief periods of hypotension sometimes need to be tolerated if mechanical compression is necessary for adequate dissection or retraction. Disruptions in venous return should be treated with vasopressors rather than volume. If volume expansion is required, a low threshold for administration of blood is often prudent, whilst at the same time limiting crystalloid use. Early consideration should also be given to fresh frozen plasma if blood transfusion is needed.
After removal of the specimen venous return should improve. Ongoing hypotension is usually related to hypovolemia, and should be corrected with colloids or blood products as indicated. If this is not the case, other complications should be considered before leaving the operating room. Aggressive bolus dosing of the thoracic epidural at this point can complicate the clinical picture. If not used during the case, it is therefore often sensible to start an epidural infusion as soon as the specimen is removed and the patient is hemodynamically stable to limit bolus requirements.
COMPLICATIONS AFTER EXTRAPLEURAL PNEUMONECTOMY
There have been several studies recently that have looked at mortality after EPP. The largest of these looked at 496 consecutive patients at a single institution.4 Four smaller current series have looked at 100, 74, 62, and 49 patients, respectively.3,17,29,30 The combined cause of mortality in these five studies is shown in Table 14–5.
Table 14–5. Cause of Mortality after Extrapleural Pneumonectomy in 779 Patients
Pulmonary embolism, myocardial infarction and acute respiratory distress syndrome (ARDS) were the three commonest causes, accounting for over 50% of the total mortality. Other cardiac causes of death were lethal cardiac arrhythmias, cardiac herniation, and right ventricular failure.
Cardiac complications that occur most frequently are dysrhythmias, myocardial ischemia and infarction, cardiac tamponade, and right ventricular failure. Other rare but serious complications relating to the pericardial patch include a restrictive physiology pattern when it is too tight, and total or partial cardiac herniation if any dehiscence occurs.
Atrial fibrillation (AF) is by far the most common cardiac (and overall) complication following EPP, with an incidence of approximately 50%.31 The etiology is multifactorial, with mechanical factors predominating. The increased pulmonary vascular resistance after removal of one lung will naturally lead to right heart distention and right atrial dilatation. Dilation of one or both atria is known to occur in over 50% of patients with chronic AF.32 In patients with postoperative AF following EPP, echocardiography demonstrates right ventricular dilatation in 75% of patients. Age less than 65 years, preoperative heart rate more than 72 beats per minute, male gender, structural abnormalities of the heart, and right heart stress have also been reported as risk factors.31,33 Conversely sympathetic blockade with thoracic epidural bupivacaine has a protective effect compared to equi-analgesic epidural narcotics.34
However, none of this explains the high incidence of AF in EPP compared to a much lower incidence of 20% in conventional pneumonectomy.19 The difference is attributed to the extensive pericardial resection that is often required during EPP. A patch reconstruction of the pericardium in right-sided EPP can also irritate the epicardium, and some studies have identified right-sided EPP as an additional risk factor.4,35
Isolated intraoperative dysrhythmias are generally triggered by mechanical irritation and do not appear to predict postoperative events. Routine attachment of ECG leads to a defibrillator in order to enable intraoperative synchronized cardioversion has been advocated.19 Postoperatively anticoagulation should be considered in patients with persistent AF less than 48 hours when the bleeding risk from the raw pleural surface has diminished.
The incidence of myocardial ischemia in EPP is not known, mainly due to the difficulty in defining ischemia. Alterations in the position of the heart during the procedure, and the difficulty in placing the V5 lead correctly in left-sided EPP add to the difficulty. Therefore, if ischemia is suspected the best monitoring tool is TEE. The incidence of myocardial infarction after EPP is 1.5% to 4%.4,17 Mild elevation in troponin levels can occur and are usually transient.
RIGHT VENTRICULAR FAILURE
Right ventricular (RV) dysfunction and failure can occur after EPP due to the increased pulmonary vascular resistance (and therefore RV afterload) encountered when the entire cardiac output needs to flow through one lung. This has a poor prognosis due to the limited contractile reserves of the RV, and there is increasing evidence for the use of nitric oxide to reduce RV afterload in this setting.36 Low doses (<10 ppm) given with the mixture of anesthetic gases for the duration of the operation has been described to try and reduce the rise in pulmonary artery pressure on completion of the pneumonectomy.3
Although rare, cardiac herniation is lethal if unrecognized. It is more common after right EPP, and is usually precipitated by an event such as a change in position of the patient, or high-intrathoracic pressures from coughing or obstructed ventilation causing dehiscence of the right-sided pericardial patch. The classic scenario occurs when the patient is turned to the supine position at the end of the procedure, and usually results in ventricular tachycardia followed by fibrillatory arrest. When the heart herniates into the right chest, venous return is severely compromised as both inferior and superior cavae become occluded. If this occurs or there is significant hypotension at this point, the patient should be immediately returned to the lateral position, followed by clean out of the chest and surgical correction. The surgeon, therefore, must be in the operating room when the patient is turned.
If the diagnosis is less obvious (ie, partial herniation) a portable chest radiograph (Figure 14–4) and TEE can aid decision making. The differential diagnosis includes hypovolemia, restrictive physiology, and tamponade.
Figure 14–4. A. The hemispheric contour from partial cardiac herniation resembles the shape of a snow cone. Clinical awareness of this sign of impending herniation is important, so risk factors known to produce herniation may be modified. B. Diagram of partial herniation to demonstrate the “snow cone” appearance.
Postoperatively if herniation occurs resuscitation can be difficult as closed cardiac compression will not be effective if the heart is empty and out of position. Early consideration should be given to emergency thoracotomy and open cardiac massage, with the only effective treatment being return of the heart to its normal position.
OTHER CARDIAC COMPLICATIONS
The incidence of postoperative cardiac tamponade is 3.6%.4 Any significant pericardial effusion can be diagnosed by TEE and should be drained. In the absence of a notable effusion, diastolic filling of the right ventricle should be carefully observed to see if a pericardial patch reconstruction is too tight. If this is the case it should immediately be revised.
Less commonly a restrictive physiology pattern can occur postoperatively if the pericardium becomes inflamed. Additionally impaired venous return can result from the diaphragmatic patch compressing the inferior vena cava.
Pulmonary complications frequently occur after EPP and are a significant cause of morbidity and mortality (Table 14–6). Early extubation and mobilization after EPP is the key to reducing pulmonary complications. Of paramount importance for this is effective thoracic epidural analgesia with a combination of local anesthetics and opioids. Epidural management should be guided by a 24-hour dedicated pain service. Frequent use of bronchoscopy to clear retained secretions is also recommended. Care should be taken to avoid postoperative fluid excess, especially with crystalloids; and aggressive diuresis may be necessary to prevent pulmonary edema.
Table 14–6. Pulmonary Complications after Extrapleural Pneumonectomy in 328 Patients36
Early detection of vocal cord dysfunction is also highly important and is often overlooked. Recurrent laryngeal nerve damage is more common after EPP, especially in patients with extensive mediastinal disease, and places the patient at high risk for aspiration and pneumonia. If a hoarse voice is present postoperatively, the patient should undergo immediate bronchoscopy to inspect the vocal cords under direct vision. If the condition is diagnosed, oral feeding should be stopped and aggressive chest physiotherapy implemented. This is followed by early surgical treatment with vocal cord medialization to prevent any further aspiration, and to restore a functional cough.
Compared to standard pneumonectomy, the extrapleural dissection in an EPP induces rapid filling of the hemithorax within the first few days postoperatively, and before the suture lines have fully healed; thus placing the patient at increased risk of empyema formation. This challenging problem is complicated by the presence of artificial patches in the field. A typical infection prophylaxis regime includes 48 hours of perioperative antibiotics and aggressive intraoperative irrigation of the chest cavity with saline.37
Clinical signs of empyema can be difficult to detect, with nonspecific features such as low-grade fevers, lethargy, and fatigue. Closed antibiotic drainage for 5 days can be used to treat empyema without bronchopleural fistula.4 In more severe cases with bronchial stump disruption open drainage and removal of the pericardial and diaphragmatic patches is recommended. This usually prevents the patient from receiving any adjuvant therapy, thus severely compromising the benefits of surgery.
Pulmonary embolism is the leading cause of death after EPP so aggressive measures should be undertaken in the prevention and treatment of deep vein thrombus. Preoperative noninvasive vascular studies are performed in some centers, with an inferior vena cava filter placed preoperatively if any clots are found.37 Sequential pneumatic compression devices (SCDs) should be used intraoperatively in all patients. Postoperatively there should be a low threshold for imaging in patients with even mild symptoms. The investigation of any unexplained oxygen desaturations should also include CT of the chest to look for evidence of pulmonary emboli.
Most diaphragmatic patch problems will manifest in the first week, if not earlier. Diagnosis in a left-sided dehiscence is usually made with a postoperative chest radiograph showing the gastric bubble in the hemithorax. Right-sided patch disruptions can be harder to diagnose as the liver is more fixed in position, and an ultrasound or CT scan is often needed to diagnose the problem.
Chylothorax is a rare problem caused by injury to the thoracic duct resulting in lymph leakage into the pneumonectomy space. Conservative therapy with no oral feeding is generally the first choice of management.38 In refractory cases lymph duct ligation may be required, and more recently percutaneous embolization of the thoracic duct has been described.39 Table 14–7 lists the most common complications after EPP and their possible causes.
Table 14–7. Complications of Extrapleural Pneumonectomy
TRIMODALITY THERAPY FOR MESOTHELIOMA
Trimodality therapy for MPM was first reported in 1991 with Sugarbaker and colleagues describing EPP with adjuvant chemotherapy and sequential radiotherapy.40 The same group have since published the largest series to date with 183 patients having a median survival of 51 months.15 Other centers have used induction chemotherapy, followed by resection and adjuvant chemotherapy.41 However, EPP after induction chemotherapy has the additional challenge of dissection through inflamed, obliterated tissue planes and immunosuppression. Chemotherapy regimens usually involve cisplatin with one or two additional agents.
Recent work has studied hyperthermic intraoperative cisplatin (HIOC). In patients with less than 1 cm3 residual tumor by direct inspection after resection, HIOC is perfused in the chest for 1 hour at 42°C. This permits higher doses to be used than would be tolerated systemically, and the higher temperature increases tumoricidal activity by increasing the metabolic activity of the cells.19 A cytoprotective agent is usually given at the same time to help protect the kidneys, but renal toxicity remains problematic.42 However, a recent phase 2 trial of HIOC showed that it can be performed safely, and might enhance local control in the chest.43
After recovery from the operation, adjunctive radiotherapy (RT) is usually initiated at 6 to 8 weeks, where a big advantage of EPP over P/D is that removal of the ipsilateral lung decreases any dose restraints. In this setting high-dose hemithoracic radiation following EPP decreases the risk of local recurrence.44 Nevertheless, the large and irregular target volume and multiple, sensitive normal structures make this strategy complex.
The most appealing RT approach after EPP is intensity-modulated radiation therapy (IMRT). IMRT is an advanced delivery technique that divides the RT treatment fields into multiple subfields of varying dose intensities; thereby making it possible to decrease the dose to a critical structure. A tumoricidal dose for gross disease is more than 60 Gy, whereas the normal tissue tolerance of adjacent tissues is much lower; for example 20 Gy for lung tissue and 40 Gy for the heart. IMRT allows target areas including all preoperative pleural surfaces and ipsilateral mediastinal lymph nodes to receive the higher dose of 50 to 60 Gy. Initial results show excellent local control with a local recurrence rate of 13% in 63 patients.17 However, the toxicity profile can be severe, and it can cause substantial toxicity to the contralateral lung, including fatal pneumonitis.45 Novel techniques such as helical tomotherapy46 and/or IMRT with the addition of electrons47 may have a role in the future.
EPP is a technically demanding operation with a high rate of perioperative morbidity. There have been significant decreases in mortality rates over the last 30 years, with improvements in surgical and anesthetic care, along with case selection.
A number of morbid conditions outlined in this review are unique to EPP. Anesthetic management of EPP requires a thorough understanding of the surgical technique and common perioperative problems. Good outcomes, therefore, require EPP to be performed in centers with extensive experience in the perioperative management of these patients, allied with a multidisciplinary approach.
Whilst mesothelioma remains a deadly disease, there is increasing evidence of a survival benefit, especially when used as a part of trimodal therapy with chemotherapy and adjuvant radiotherapy. An aggressive approach can be undertaken with low mortality and acceptable morbidity in carefully selected patients.
1. Sarot IA. Extrapleural pneumonectomy and pleurectomy in pulmonary tuberculosis. Thorax. 1949;4: 173-223.
2. Opitz I, Kestenholz P, Lardinois D, et al. Incidence and management of complications after neoadjuvant chemotherapy followed by extrapleural pneumonectomy for malignant pleural mesothelioma. Eur J Cardio-Thorac Surg. 2006;29(4):579-584.
3. Stewart DJ, Martin-Ucar AE, Edwards JG, et al. Extra-pleural pneumonectomy for malignant pleural mesothelioma: the risks of induction chemotherapy, right-sided procedures and prolonged operations.Eur J Cardio-Thorac Surg. 2005;27(3):373-378.
4. Sugarbaker DJ, Jaklitsch MT, Bueno R, et al. Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg. 2004;128(1):138-146.
5. Butchart EG, Ashcroft T, Barnsley WC, et al. Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. Thorax. 1976;31(1):15-24.
6. Ismail-Khan R, Robinson LA, Williams CC Jr, Garrett CR, Bepler G, Simon GR. Malignant pleural mesothelioma: a comprehensive review. Cancer Control. 2006;13(4):255-263.
7. Wagner J. Diffuse pleural mesothelioma and asbestos exposure in the North West Cape Province. Br J Ind Med. 1960;17:260-271.
8. Cugell DW, Kamp DW. Asbestos and the pleura: a review. Chest. 2004;125(3):1103-1117.
9. Robinson BWS, Lake RA. Advances in malignant mesothelioma. N Engl J Med. 2005;353(15):1591-1603.
10. Boutin C, Rey F. Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 1: diagnosis. Cancer. 1993;72(2):389-393.
11. Weiner SJ, Neragi-Miandoab S. Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors. J Cancer Res Clin Oncol. 2009;135(1):15-27.
12. Ceresoli GL, Gridelli C, Santoro A. Multidisciplinary treatment of malignant pleural mesothelioma. Oncologist. 2007;12(7):850-863.
13. Flores RM, Pass HI, Seshan VE, et al. Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg. 2008;135(3):620-626.
14. Flores RM, Krug LM, Rosenzweig KE, et al. Induction chemotherapy, extrapleural pneumonectomy, and postoperative high-dose radiotherapy for locally advanced malignant pleural mesothelioma: a phase II trial. J Thorac Oncol. 2006;1(4):289-295.
15. 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. 1999;117(1):54-63; discussion -5.
16. Weder W, Kestenholz P, Taverna C, et al. Neoadjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma. J Clin Oncol. 2004;22(17):3451-3457.
17. Rice DC, Stevens CW, Correa AM, et al. Outcomes after extrapleural pneumonectomy and intensity-modulated radiation therapy for malignant pleural mesothelioma. Ann Thorac Surg. 2007;84(5):1685-1692; discussion 92-93.
18. Treasure T, Lang-Lazdunski L, Waller D, Bliss JM, et al. Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study. Lancet Oncol. 2011;12(8):763-772.
19. Ng J-M, Hartigan PM. Anesthetic management of patients undergoing extrapleural pneumonectomy for mesothelioma. Curr Opin Anaesthesiol. 2008;21(1):21-27.
20. British Thoracic Society Standards of Care Committee. Statement on malignant mesothelioma in the United Kingdom.[see comment][erratum appears in Thorax. 2001 Oct;56(10):820]. Thorax. 2001;56(4):250-265.
21. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655.
22. Yan TD, Boyer M, Tin MM, et al. Prognostic features of long-term survivors after surgical management of malignant pleural mesothelioma. Ann Thorac Surg. 2009;87(4):1552-1556.
23. Rusch VW. A proposed new international TNM staging system for malignant pleural mesothelioma. From the International Mesothelioma Interest Group. Chest. 1995;108(4):1122-1128.
24. Wittnich C, Trudel J, Zidulka A, Chiu RC. Misleading “pulmonary wedge pressure” after pneumonectomy: its importance in postoperative fluid therapy. Ann Thorac Surg. 1986;42(2):192-196.
25. Ballantyne JC, Carr DB, deFerranti S, et al. The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anesth Analgesia. 1998;86(3):598-612.
26. Katz J, Jackson M, Kavanagh BP, et al. Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. Clin J Pain. 1996;12(1):50-55.
27. Agnew NM, Kendall JB, Akrofi M, et al. Gastroesophageal reflux and tracheal aspiration in the thoracotomy position: should ranitidine premedication be routine? Anesth Analg. 2002;95(6):1645-1649.
28. Sanjay PS, Miller SA, Corry PR, et al. The effect of gel lubrication on cuff leakage of double lumen tubes during thoracic surgery. Anaesthesia. 2006;61(2):133-137.
29. de Perrot M, McRae K, Anraku M, et al. Risk factors for major complications after extrapleural pneumonectomy for malignant pleural mesothelioma. Ann Thorac Surg. 2008;85(4):1206-1210.
30. Aigner C, Hoda MAR, Lang G, et al. Outcome after extrapleural pneumonectomy for malignant pleural mesothelioma. Eur J Cardio-Thorac Surg. 2008;34(1):204-207.
31. Neragi-Miandoab S, Weiner S, Sugarbaker DJ. Incidence of atrial fibrillation after extrapleural pneumonectomy vs pleurectomy in patients with malignant pleural mesothelioma. Interact Cardiovasc Thorac Surg. 2008;7(6):1039-1042.
32. Xiao HB, Rizvi SAH, McCrea D, et al. The association of chronic atrial fibrillation with right atrial dilatation and left ventricular dysfunction in the elderly. Med Sci Monit. 2004;10(9):CR516-520.
33. Hirose M, Takeishi Y, Miyamoto T, et al. Mechanism for atrial tachyarrhythmia in chronic volume overload-induced dilated atria. J Cardiovasc Electrophysiol. 2005;16(7):760-769.
34. Oka T, Ozawa Y, Ohkubo Y. Thoracic epidural bupivacaine attenuates supraventricular tachyarrhythmias after pulmonary resection. Anesth Analgesia. 2001;93(2):253-259.
35. Harpole DH, Liptay MJ, DeCamp MM Jr, et al. Prospective analysis of pneumonectomy: risk factors for major morbidity and cardiac dysrhythmias. Ann Thorac Surg. 1996;61(3):977-982.
36. McNeil K, Dunning J, Morrell NW. The pulmonary physician in critical care. 13: the pulmonary circulation and right ventricular failure in the ITU. Thorax. 2003;58(2):157-162.
37. Zellos L, Jaklitsch MT, Al-Mourgi MA, et al. Complications of extrapleural pneumonectomy. Semin Thorac Cardiovasc Surg. 2007;19(4):355-359.
38. Tokunaga T, Inoue M, Ideguchi K, et al. Late-onset chylothorax following etrapleural pneumonectomy for mesothelioma. Gen Thorac Cardiovasc Surg. 2007;55(2):50-52.
39. Hoffer EK, Bloch RD, Mulligan MS, et al. Treatment of chylothorax: percutaneous catheterization and embolization of the thoracic duct. Am J Roentgenol. 2001;176(4):1040-1042.
40. Sugarbaker DJ, Mentzer SJ, DeCamp M, et al. Extrapleural pneumonectomy in the setting of a multi-modality approach to malignant mesothelioma. Chest. 1993;103(4 Suppl):377S-381S.
41. Buduhan G, Menon S, Aye R, et al. Trimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg. 2009;88(3):870-875; discussion 6.
42. Zellos L, Richards WG, Capalbo L, et al. A phase I study of extrapleural pneumonectomy and intracavitary intraoperative hyperthermic cisplatin with amifostine cytoprotection for malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2009;137(2):453-458.
43. Tilleman TR, Richards WG, Zellos L, et al. Extrapleural pneumonectomy followed by intracavitary intraoperative hyperthermic cisplatin with pharmacologic cytoprotection for treatment of malignant pleural mesothelioma: a phase II prospective study. J Thorac Cardiovasc Surg. 2009;138(2):405-411.
44. Rusch VW, Rosenzweig K, Venkatraman E, et al. A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2001;122(4):788-795.
45. Miles EF, Larrier NA, Kelsey CR, et al. Intensity-modulated radiotherapy for resected mesothelioma: the Duke experience. Int J Radiat Oncol Biol Phys. 2008;71(4):1143-1150.
46. Sterzing F, Sroka-Perez G, Schubert K, et al. Evaluating target coverage and normal tissue sparing in the adjuvant radiotherapy of malignant pleural mesothelioma: helical tomotherapy compared with step-and-shoot IMRT. Radiother Oncol. 2008;86(2):251-257.
47. Chan MF, Chui CS, Song Y, et al. A novel radiation therapy technique for malignant pleural mesothelioma combining electrons with intensity-modulated photons. Radiother Oncol. 2006;79(2):218-223.