Elie Fadel and Philippe Dartevelle
INDICATIONS/CONTRAINDICATIONS
Until recently, the use of cardiopulmonary bypass (CPB) during the resection of advanced thoracic malignancies was highly controversial. Although technical advances have considerably improved the safety of CPB, the poor prognosis of advanced thoracic malignancies may suggest an unfavorable risk/benefit ratio. CPB adversely affects hemostasis and lung function and has been hypothesized to induce hematogenous tumor dissemination. Finally, some surgeons may lack the knowledge needed to manage CPB during extensive thoracic resections.
Complete en bloc resection remains the best means of improving survival in patients with thoracic malignancies. However, complete en bloc resection is difficult to achieve in tumors, invading the great vessels or heart, which are, therefore, often considered inoperable. This view has been challenged in recent years by reports of excellent outcomes after the surgical resection of primary cardiac tumors under CPB. As a result, some thoracic surgeons are reconsidering the use of CPB in oncologic thoracic surgery. A few recently published small case series studies support the technical feasibility of this approach and suggest that it can provide excellent long-term outcomes.
Indications
The use of CPB during surgical resection of thoracic malignancies should be considered only in carefully selected patients after a multidisciplinary evaluation and discussion of all treatment options. The multidisciplinary team should include skilled thoracic surgeons (trained in the use of CPB and in vascular surgery), an oncologist, an anesthesiologist, an intensivist, and a radiologist.
The complexity of the surgical procedure, high risk of morbidity and mortality, and poor prognosis of incompletely resected thoracic tumors require rigorous patient selection. Patients can benefit from these radical procedures only if complete microscopic resection is achieved.
Elective procedures should be performed with curative intent according to the well-established principles of oncologic surgery (en bloc surgery with microscopically tumor-free margins). Under no circumstances should they be performed with palliative intent.
The need for CPB may be related either to the sites of tumor involvement or to intraoperative events. CPB is helpful when the tumor involves the aorta, left atrium/pulmonary veins, pulmonary arteries, and/or right atrium/inferior and superior vena cava (SVC) complex. In this situation, the decision to use CPB is taken preoperatively based on the results of the staging workup then confirmed intraoperatively when the tumor is seen to invade the thoracic aorta (ascending, arch, and descending), left subclavian or innominate artery down to the aortic arch, common pulmonary artery up to its bifurcation, and/or cardiac chambers (left or right atrium). In these situations, the use of the CPB is mandatory to avoid hemodynamic instability or tumor embolization and to allow complete resection with safe margins. Furthermore, in a small subset of patients, intraoperative events require the use of CPB on an emergency basis. These events may consist in injury to the great mediastinal vessels or heart during tumor resection or in difficulties with ventilation or hemodynamic control during the resection of central tumors. CPB may facilitate, or provide the necessary safety net to achieve, complete surgical resection. CPB is an established alternative to ventilation during extended resections; it provides both oxygenation and hemodynamic stability. The main situations requiring emergent CPB use are the resection of thoracic malignancies involving the trachea or carina, during which adequate oxygenation may be difficult to achieve with conventional ventilation; and the resection of large thoracic tumors invading the SVC or responsible for heart and lung compression, which may result in hemodynamic instability, particularly in case of injury to the SVC, inferior vena cava (IVC), or pulmonary artery. CPB, by allowing rapid filling, may restore hemodynamic stability. With CPB, cardiorespiratory function remains stable throughout the surgical procedure and the heart can be retracted to the side as much as needed.
Contraindications
There are two absolute contraindications to the elective surgical resection of extended thoracic malignancies under CPB: A predicted inability to achieve complete resection, and poor general health or severe comorbidities jeopardizing survival even in the event of complete resection. In all other situations, the decision to perform tumor resection with CPB is taken on a case-by-case basis during a multidisciplinary conference. The factors taken into account include the biologic tumor features (aggressiveness, responsiveness to chemotherapy, and resectability), symptoms, and performance status of the patient. For example, aggressive surgery may be warranted in young patients with residual nonseminomatous germ cell tumor (NSGCT) after chemotherapy even those with removable distant metastases but is not appropriate in patients with nonsmall-cell lung cancer (NSCLC) and distant metastases.
PREOPERATIVE PLANNING
A careful preoperative workup should be performed to predict the likelihood of achieving complete tumor resection with an acceptable level of risk. Both the features of the tumor and the functional status of the patient should be assessed.
Evaluation of the Tumor
Histologic confirmation must be obtained before establishing the treatment plan, except for NSGCTs with increased serum tumor markers. The biopsy can be collected by direct sampling under local or general anesthesia, flexible bronchoscopy, or needle aspiration under computed tomography (CT) or ultrasound guidance. Subsequent investigations depend in large measure on the histologic findings. Investigations obtained routinely to assess local tumor spread include chest roentgenograms; CT angiography of the neck, chest, and abdomen; flexible bronchoscopy; transthoracic echocardiography; and Duplex scanning of the carotid, vertebral, and subclavian arteries on both sides to check patency. In patients with NSCLC, endobronchial ultrasound is now routinely performed to exclude mediastinal lymph node involvement; when this investigation is not available, mediastinoscopy should be performed prior to extended surgery if CT shows one or more mediastinal lymph nodes. In patients with aortic involvement, the workup may benefit from angiography of the aortic arch and supra-aortic trunks and from transesophageal ultrasound to determine whether left subclavian artery involvement extends to the esophageal wall. When the SVC or an innominate vein is involved by the tumor, phlebocavography by simultaneous injection into a forearm vein on both sides can provide invaluable information to the surgeon. Occlusion of both innominate veins contraindicates CPB, as the poor venous drainage carries a high risk of brain edema (Fig. 45.1). Magnetic resonance imaging (MRI) is very helpful to assess invasion of the intervertebral foramen or spine, heart (cardio-MRI), and IVC. Distant tumor spread is evaluated routinely by positron emission tomography-CT, cerebral CT, or MRI. Depending on the symptoms, subsequent investigations may consist of bone scintigraphy, bone MRI, and/or liver ultrasound to look for distant metastases.
Figure 45.1 Phlebocavography by simultaneous injection into a forearm vein on both sides showing occlusion of both innominate veins.
Evaluation of the Patient’s Functional Status
The functional status of the patient should be assessed before treatment decisions are made. Cardiopulmonary function must be sufficient to allow a long surgical procedure. In addition to the standard preoperative laboratory and respiratory function tests, standard echocardiography should be performed routinely to rule out pulmonary hypertension, left ventricle dysfunction, severe valvular disease, and pericardial effusion. Depending on patient- and tumor-related factors, various other tests may be in order. Coronary angiography should be performed in patients at risk for coronary artery disease. Patients scheduled for pneumonectomy should undergo ventilation/perfusion scanning and right heart catheterization to measure mean pulmonary artery pressure, cardiac output, and pulmonary vascular resistance before and after balloon occlusion of the involved pulmonary artery. This last investigation may show pulmonary hypertension, which precludes surgery. In selected patients, the maximal oxygen uptake can be assessed.
The results of this comprehensive workup allow an assessment of tumor-related factors (local and distant extension, histology, aggressiveness, and availability of active chemotherapy) and patient-related factors (symptom severity and functional status) that serves to establish the surgical indications during a multidisciplinary conference. When designing multimodality treatment regimens, adjuvant treatments (i.e., chemotherapy, radiation therapy, or both) should be preferred over neoadjuvant therapy, which may induce a decline in general health associated with poorer outcomes of the complex surgical procedure. However, neoadjuvant therapy is mandatory in some histologic tumor types such as germ cell tumors and sarcomas.
Planning of the Cardiopulmonary Bypass Technique
Conventional CPB allows cardiac surgery in a motionless and bloodless field. The extracorporeal circuit and membrane oxygenator used to provide physiologic support require full anticoagulation, which may increase the risk of excessive bleeding requiring blood transfusion and, subsequently, of pneumonia following thoracic tumor resection. Conventional CPB must be used when cardiac arrest is required, for instance when the tumor involves the heart, requiring opening of the cardiac chambers, or infiltrates the aortic arch or common pulmonary artery. Conventional CPB may be helpful in highly selected complex cases, by allowing circulatory arrest under deep hypothermia. However, to avoid bleeding-related complications, the use of extracorporeal membrane oxygenation (ECMO) has been suggested. ECMO does not require cardiac arrest. This technique is particularly useful when stabilization of hemodynamics and/or oxygenation is required due to large tumor size, heart-chamber compression, or ventilatory difficulties. ECMO does not require full anticoagulation, as the circuit is heparin coated, and therefore constitutes an attractive alternative to conventional CPB. Intraoperative administration of a single heparin dose of 70 International Unit/kg body weight is usually adequate. The target activated clotting time is 180 to 200 seconds whereas a minimum of 300 seconds is required during conventional CPB. In addition, ECMO is less likely to induce tumor-cell dissemination, as it involves a closed loop with no suction from the operative field and therefore no reintroduction into the general circulation of tumor debris and cytokines. With ECMO, the systemic inflammatory reaction induced by contact of blood with air and artificial surfaces is less marked and the tubing system less cumbersome than with conventional CPB. A venoarterial circuit can be used when hemodynamic stabilization is required or a venovenous circuit when the only concern is the occurrence of ventilatory difficulties, for instance during carinal resection.
Another alternative to conventional CPB for thoracic tumor resection is pumpless interventional lung assist (iLA). The successful use of this technique in two patients was reported recently. The iLA device is a membrane oxygenator allowing CO2 elimination and may, therefore, constitute an alternative to venovenous ECMO.
SURGERY
Given the small number of patients who undergo extended thoracic tumor resection with CPB, together with the considerable variability in the clinical and anatomical presentations of these tumors, the surgical techniques are not standardized. To achieve en bloc complete microscopic R0 resection, the surgeon must adapt the procedure to the characteristics of the tumor as assessed during the preoperative workup for scheduled surgery or during the operative exploration in emergent surgery. Furthermore, the surgical plan may need to be modified at any time depending on the operative findings. Close cooperation among team members including the surgeon, anesthesiologist, and perfusionist is mandatory.
Patient Positioning and Surgical Approach
The surgical approach is chosen based on the need to achieve complete en bloc resection followed by reconstruction of vital anatomic structures. With the wide possibilities of vascular access as cannulation sites and the different type of arterial and venous cannulas currently available, the use of the CPB is rarely critical for the choice of the surgical approach. For extended thoracic tumor resections, we recommend the routine preparation and inclusion within the operative field of a peripheral cannulation site (femoral or axillary). The most widely used approaches are median sternotomy, posterolateral thoracotomy, and the clamshell incision. Some patients may require median sternolaparotomy, anterior transclavicular thoracotomy, or combined approaches. The most commonly used arterial cannulation sites are the ascending aorta, descending aorta, and femoral artery. Venous access is usually bicaval, atrial, femoral (cannula placed in the right atrium via the femoral vein), pulmonary arterial, and/or intra-abdominal caval.
General Considerations
To decrease the risk of bleeding, the tumor is dissected free from the involved structures as far as possible before the initiation of systemic anticoagulation. In patients with a mobile malignant thrombus, for instance in lung cancer involving the left atrium (Fig. 45.2), the high risk of systemic tumor embolism during tumor dissection is a major concern. In this situation, CPB, cardiac arrest, and aortic cross clamping must precede tumor manipulation. The surgical procedure starts with a thorough intraoperative inspection to assess tumor spread and resectability. In most patients, several mediastinal and cardiac structures are affected simultaneously. A meticulous inspection must be performed prior to the irreversible removal of any vital structures. For most tumors, free-margin resection must be confirmed by repeated intraoperative frozen sections. In patients who have received induction therapy, particularly radiation therapy, the resection borders may be difficult to define. They should be chosen based on tumor extension before induction therapy.
For complex surgical procedures, for instance to remove primary pulmonary artery sarcoma or tumors involving the right cardiac chambers and IVC, circulatory arrest under deep hypothermia is very useful. This technique may facilitate surgery by improving operative field exposure (avoidance of multiple cannulas and bloodless operating field). In contradiction to a report by Wiebe et al., subsequent studies have established that deep hypothermia does not increase the risk of postoperative pulmonary dysfunction.
Figure 45.2 Thoracic CT scan showing a mobile malignant thrombus into the left atrium originating from a lung cancer.
Due to the long operative time, frequent need for blood transfusion, and potential risk of septic contamination due to airway opening, infection of the operating field is a major risk. Therefore, whenever feasible, primary repair should be preferred over prosthetic replacement. However, when direct suture would result in tension due to the extent of the resection, grafting can be performed using autologous or heterologous pericardium, Dacron, or polytetrafluoroethylene (PTFE), followed by coverage with a local pedicled flap (fat, pleura, or muscle) in patients at high risk for infection.
Technique
Thoracic Inlet Tumor Involving the Left Subclavian Artery and Distal Aortic Arch
The anterior transcervical approach is preferred to allow thoracic inlet dissection at a distance from the tumor (Fig. 45.3). This step provides confirmation that the tumor is resectable. Releasing the esophageal and tracheal walls into the upper mediastinum establishes that the esophagus and trachea are uninvolved. The left subclavian artery is severed distal to the tumor and anastomosed in terminolateral fashion to the left carotid artery, provided this vessel is not invaded by the tumor. This approach allows the resection of invaded structures (clavicle, ribs, vessels, nerves, and transverse processes). When vertebral resection requiring spinal fixation must be performed, the risk of major bleeding precludes other resections that would mandate CPB. The patient is then turned in right lateral decubitus and a left posterolateral thoracotomy is performed. After lung resection, the aortic arch can then be dissected. CPB is initiated between the main pulmonary artery and descending aorta, allowing cross clamping of the aorta proximally, upstream to the left subclavian or carotid artery and to the descending aorta distally. The space is very tight between the origin of the left subclavian artery and the left common carotid artery, and the proximal clamp on the aortic arch may, therefore, include part of the left common carotid artery to provide enough space for reconstruction and further resection. The aorta can also be cross clamped between the innominate artery and the left carotid artery to resect the distal part of the aortic arch and origin of the subclavian artery. The resected aorta can be reconstructed using a graft (Dacron) patch or tube, depending on the extent of the resection.
Figure 45.3 Arteriography showing a thoracic inlet tumor involving the left subclavian artery up to the distal aortic arch.
Resection of the Descending Aorta
Aortic invasion by NSCLC is usually limited to the adventitia. It is very difficult to rule out deeper aortic invasion during the preoperative workup. In rare instances, the aortic media is also invaded, and resection then requires cross clamping of the aorta proximally and distally to remove the infiltrated wall. CPB is the easiest way to achieve perfusion of the upper and lower part of the body during aortic cross clamping. The patient is positioned in right lateral decubitus, a left posterolateral thoracotomy is performed through the fifth intercostal space, the tumor is dissected from the surrounded structures, and the patient is placed under CPB with the venous cannula inserted in the main pulmonary artery and the arterial cannula in the descending aorta, distal to the tumor (Fig. 45.4). The descending aorta is cross clamped proximally and distally to the tumor and resected. Perfusion of the upper part of the body is thus achieved by the beating heart and perfusion of the lower part of the body by normothermic partial bypass. Adequate perfusion of the upper part of the body is controlled via an arterial line in the right radial artery. The flow is started at 50% of the estimated cardiac output and adjusted to the hemodynamic and gas exchange needs. Cannulation of the main pulmonary artery and descending aorta through a left posterolateral thoracotomy can also be useful when the wall of the descending aorta is unexpectedly found to be invaded by the tumor and the femoral vessels were not kept in the operating field. With this technique, the venous cannula should be placed proximally in the left pulmonary artery after having cut the arterial ligament, and the tip of the venous cannula should be placed in the main pulmonary artery or right ventricle (Fig. 45.5). Care should be taken to avoid placing the tip of the cannula in the right pulmonary artery, which might impair right ventricular ejection. When the tumor invades the aortic arch more proximally than the left carotid artery, or when the lesser curvature of the aortic arch is invaded, CPB with selective cerebral perfusion or circulatory arrest may be required. An alternative to the descending aorta for arterial cannulation is the left femoral artery through the left groin. For venous access, the cannula inserted through the femoral vein should be long enough to reach the right atrium to ensure sufficient flow. Because of the patient position in lateral decubitus during the surgical procedure, it may be difficult and risky to advance this venous cannula up to the heart. A recently reported alternative in left lung resections extended to the pulmonary artery trunk consists in inserting the venous cannula into the right atrium in the operating field through the pericardium. The right atrium is approached in front of the heart that may induce hemodynamic instability. A Dacron vascular prosthesis is usually implanted for reconstruction.
Figure 45.4 Operative view with a left posterolateral thoracotomy performed through the fifth intercostal space. The CPB is instituted with the venous cannula inserted in the main pulmonary artery (A) and the arterial cannula in the descending aorta, distal to the tumor (B). C,D:The operative field with cannulae inserted.
Figure 45.5 Placement of the venous cannula in the left pulmonary artery with the tip placed in the main pulmonary artery or right ventricle (A) and not in the right pulmonary artery (B).
Resection of the Pulmonary Artery Bifurcation and Left Atrium
In patients with lung cancer invading the pulmonary veins up to the left atrium, complete resection is usually achieved by placing a vascular clamp on the left atrium to remove the tumor along with both pulmonary veins then directly suturing the defect. However, if a large portion of the left atrium is invaded, there is often extensive microscopic infiltration of the myocardium precluding complete tumor resection. Also, tumor extension into the left atrial lumen carries a high risk of systemic tumor embolization after direct clamping of the left atrium. In these cases, CPB is useful to resect the left atrium or origin of the left pulmonary artery. Similarly, complete resection of central tumors invading the origin of the left main pulmonary artery must be followed by reconstruction of the pulmonary arterial trunk. In both situations, the tumor is preferentially approached through a median sternotomy to enable central cannulation, aortic clamping, cardioplegia, and de-airing. The pericardium is opened and the cannulas placed into the SVC, IVC, and ascending aorta. Both pulmonary veins can be stapled inside the pericardium. The left atrium can be stapled at a distance from the pulmonary vein ostia to allow complete resection of the tumor extending into the left atrium. In case of substantial tumor extension inside the left atrium with a high risk of tumor embolism toward the systemic circulation during manipulation of the heart (Fig. 45.1), particularly when clamping the left atrium, cardiac arrest is mandatory after anterograde cardioplegia and aortic cross clamping to allow cardiac luxation. The left atrium is opened in a tumor-free zone with continuous pericardial suction to produce a bloodless operative field. After complete resection of the left atrium, direct suture is generally performed using a return Prolene 4-0 suture. When suture of the left atrium is likely to result in a very small chamber, implantation of an autologous or heterologous pericardial patch can produce a sufficiently large left atrial chamber to allow diastolic filling of the left ventricle. In tumors extending up to the origin of the left pulmonary artery or even to the pulmonary arterial trunk, through this approach, snaring of both venae cavae and cardiac arrest facilitates tumor resection by allowing cardiac luxation toward the right side. The pulmonary arterial tree is opened without clamping and reconstructed using an autologous or heterologous patch to avoid stenosis. Exceptionally, pulmonary route reconstruction requires a tubular prosthetic graft, preferably a PTFE or Dacron ringed tube, which is implanted between the proximal pulmonary arterial trunk and right pulmonary artery, under the aortic arch concavity.
Resection of the Trachea or Carina
In most patients with tumors involving the trachea, carina, or lung and tracheobronchial bifurcation, tumor resection and airway reconstruction are performed without CPB. However, CPB may be required when pulmonary edema compromises ventilation of the lung through the operative field. In this situation, CPB allows completion of the airway anastomoses without tension on the suture lines. During carinal pneumonectomy, if pulmonary edema of the contralateral lung develops, CPB should be started early during the procedure to avoid further lung injury from mechanical ventilation and to allow tension-free tracheal anastomosis. Either conventional CPB or ECMO may be used in these situations since there is no need for cardiac arrest. Carinal resection is usually performed through a right posterolateral thoracotomy when invasion originates from the right lung. In most cases, lung resection is performed also. CPB is initiated between the right atrium and ascending aorta to allow completion of the tracheal anastomosis. For primary carinal tumors without extension to the lung and for carinal invasion originating from the left lung, a median sternotomy is preferred, with CPB between the right atrium and ascending aorta. The femoral artery can be used as an alternative to the ascending aorta for cannulation, particularly in patients with extensive aortic calcifications.
Resection of Large Mediastinal Tumors
In most patients with mediastinal tumors even when the SVC is invaded, resection does not require CPB. A median sternotomy is usually deemed appropriate. Hemodynamic instability may occur in large tumors with right heart compression. Conventional CPB or ECMO with an arterial femoral access and a venous cannula inserted into the right atrium may be helpful to achieve tumor resection. The femoral access disencumbers the operative field. When tumor extends to the right atrium (Fig. 45.6), a conventional CPB is mandatory with the venous cannula inserted in the IVC.
Figure 45.6 A: Thoracic angioCT scan showing a thymic carcinoma invading the superior vena cava up to the right atrium. B: The operative view through a median sternotomy with an arterial cannula inserted in the ascending aorta and the venous cannula in the inferior vena cava. The superior vena cava was replaced by a ringed PTFE graft between the left innominate vein and the cavo-atrial junction.
Resection of Tumors Invading the Inferior Vena Cava and Right Heart Chambers
Resection of primary IVC tumors or of tumors originating elsewhere and invading the IVC (usually by direct endovascular extension) may require CPB when the inferior cavoatrial junction is involved. The most common indications are IVC sarcoma, renal cell cancer, and NSGCT of the testis. The tumor may extend up to the pulmonary arteries through the right heart chambers. The best approach to these tumors is a median sternotomy and supraumbilical laparotomy. Full liver mobilization is required to provide access to the intrahepatic portion of the IVC. The left triangular ligament and falciform ligament are divided, and the central diaphragmatic tendon is dissected on the midline until identification of the supradiaphragmatic intrapericardial IVC and hepatic veins. The liver is rolled toward the patient’s right side to expose the junction between the hepatic veins, proximal IVC, and right atrium. The pericardium is opened and the intracardiac IVC is controlled. Rotation of the liver to the right fully exposes the retrohepatic IVC, from the renal veins to the right atrium, and facilitates venotomy from the right atrium to the infrahepatic IVC. The porta hepatis is controlled with a Rummel tourniquet or vascular clamp to allow Pringle maneuver (Fig. 45.7). The tumor is then resected (nephrectomy, adrenalectomy, hepatectomy, etc.) and the lymph nodes dissected when necessary. Hemostasis is achieved before CPB initiation. The ascending aorta is cannulated in the standard fashion. Venous drainage is ensured by inserting a cannula into the SVC and another into the IVC below the tumor thrombus, in the retrograde direction (usually below the renal veins). The IVC, SVC, and hepatic artery and porta are snared as well during CPB to decrease bleeding. When the tumor extends up toward the pulmonary arteries or a pulmonary tumor embolus is found, cardiac arrest with aortic cross clamping is required. Deep hypothermia (18°C) with circulatory arrest is often helpful to perform pulmonary endarterectomy when the tumor extends into both pulmonary arteries.
Figure 45.7 Median sternotomy and supraumbilical laparotomy allowing removal of tumors invading the right heart chambers and the inferior vena cava.
Use of CPB to Manage Life-threatening Situations
When a right thoracotomy has been performed, emergent cannulation is easily achieved via the ascending aorta and right atrium. In patients with a left thoracotomy, cannulation can be achieved via the descending thoracic aorta and main pulmonary artery, directing the cannulae into the right ventricle. As mentioned above, in the lateral decubitus position, femoral vein cannulation for CPB is much more difficult. In this situation, another option for venous cannulation may consist in opening the pericardium and cannulating the right atrium. However, this maneuver is highly variable and may be dangerous in emergent situation.
POSTOPERATIVE MANAGEMENT
The postoperative management is generally performed in the intensive care unit (ICU). The long operating time, frequent need for blood transfusions, and pulmonary resection preclude early extubation. Gradual awakening prevents blood pressure elevation and pulmonary edema, especially after pneumonectomy. During the first 24 hours, the following should be monitored routinely:
Body temperature, to avoid hypothermia, a common complication of prolonged surgery, bleeding, and CPB.
Hemodynamics, via the conventional methods used in thoracic surgery combined with an arterial line in either the radial or the femoral artery, a urinary Foley catheter, and a Swan–Ganz pulmonary artery catheter (to measure left-sided filling pressures, mixed venous oxygen saturation, pulmonary artery pressures, and cardiac output). After surgery with cardiac arrest, pacing wires (atrial and ventricular) should be implanted before chest closure and used when necessary. The data provided by these monitoring procedures serve to guide fluid resuscitation and hemodynamic support.
Control of bleeding through the chest tubes and repeated chest radiographs. After aortic replacement, anticoagulation is not required and a single antiplatelet agent is sufficient. Effective anticoagulation must be given after vena cava replacement or innominate vein ligation.
Emergence from anesthesia and ventilatory support in selected patients, early extubation can be performed depending on the patient’s functional status and on the extent of the surgical procedure. However, most patients require gradual stabilization of the hemodynamic and ventilatory parameters followed by extubation on the following morning.
COMPLICATIONS
In addition to the complications often seen after general thoracic surgery (such as pneumonia, pleural effusion, empyema, pulmonary embolism, acute respiratory distress syndrome [ARDS] requiring prolonged mechanical ventilation, and atrial fibrillation), a number of events may be seen after CPB for extended thoracic tumor resections.
Pulmonary Edema and Subsequent Respiratory Failure
This complication has been reported in as many as 37% of patients after resection of thoracic malignancies with CPB. CPB is known to induce lung injury and ARDS, and the risk is increased when pulmonary resection, particularly pneumonectomy, is performed during the same procedure or when the use of CPB is prolonged. Pulmonary edema is the main cause of death after pneumonectomy. In a study of thoracic malignancy resection with CPB, Wiebe et al. found a 22% mortality rate after pneumonectomy whereas no patients died after lobectomy. The main underlying mechanism is an inflammatory response to CPB with activation of the complement and coagulation systems; activation of the fibrinolytic and kallikrein cascades; and activation of neutrophils with degranulation, protease enzyme release, production of oxygen radicals, and production of various cytokines by mononuclear cells. As mentioned above, ECMO seems associated with a lower risk of lung injury.
Bleeding
The risk of intraoperative bleeding is increased by systemic heparin therapy, particularly when extensive resection such as pneumonectomy is performed. In our experience, the risk can be decreased by dissecting the tumor free from the involved structures as far as possible before starting systemic anticoagulation and CPB. Reoperation for bleeding is required in 10% to 21% of patients.
Systemic Tumor Dissemination
Risk factors may consist of recirculation of blood suctioned from the operative field, immune system alterations, and CPB-induced pan-endothelial injury. However, this risk is currently theoretical, and there is no scientific evidence supporting increased systemic tumor-cell spread during CPB. The risk of distant metastasis is high in these large and aggressive tumors even when CPB is not used, and extensive surgery should be viewed as only one of the components of a multimodality therapeutic strategy.
TABLE 45.1 Early Outcomes Reported after Resection of Thoracic Malignancies with Cardiopulmonary Bypass
Other complications attributable to CPB may include groin infection, stroke, or low cardiac output syndrome requiring inotropic drug administration to allow separation from the CPB. These complications are common after prolonged CPB, regardless of its indications.
RESULTS
CPB is estimated to be required in less than 0.1% of all patients undergoing thoracic malignancy resection. Consequently, the only outcome data come from anecdotal case reports or small case series studies. Furthermore, resection with CPB is performed for a wide variety of thoracic malignancies including mediastinal sarcoma, mesothelioma, carcinoid tumor, and NSCLC. NSCLC constitutes the largest and most homogeneous group, as sarcomas cover a broad range of histologic types of variable aggressiveness. Postoperative morbidity and mortality rates ranged from 45% to 63% and from 0% to 15%, respectively, as shown in Table 45.1 together with the rate of complete R0 resections.
Patients with advanced NSCLC invading the mediastinum had a poor prognosis. Thus, 5-year survival rates reported for stage IIIB NSCLC ranged from 3% to 7% with a median survival of 13.7 months after chemotherapy and radiation therapy and 9.6 months after radiation therapy alone. In a systematic review of all studies on NSCLC resected using CPB and published as of 2011, Muralidaran et al. identified 20 studies with a total of 71 patients. Overall 5-year survival was 37% with a median survival of 36 months. The only independent factor that significantly affected survival by multivariate analysis was planned use of CPB, which was associated with significantly higher survival than unplanned/emergency CPB (P = 0.033). The type of CPB, tumor histology, induction therapy, and type of surgical approach did not significantly affect survival. Most authors agree that CPB-supported surgical treatment deserves consideration in patients with T4 N0 disease.
Primary pulmonary and mediastinal sarcomas are heterogeneous tumors that vary in their clinical presentation. We deliberately excluded primary pulmonary artery sarcoma, which mimics chronic thromboembolic pulmonary hypertension and requires surgery under deep hypothermic circulatory arrest, as used for pulmonary endarterectomy. Surgery is chiefly performed for palliation or to allow adjuvant chemotherapy. In other types of remaining pulmonary and mediastinal sarcomas requiring resection with CPB, complete surgical resection is the primary goal. Reported 5-year survival rates range from 48% to 69% and are thus considerably higher than in patients with NSCLC.
CONCLUSIONS
In most thoracic malignancies, complete resection is the main treatment and can result in long-term survival. The use of CPB in highly selected patients allows complete resection of extended thoracic malignancies that would not be resectable otherwise. The appropriateness of surgery should be assessed by a multidisciplinary team based on the functional status of the patient, features of the tumor, and expected benefits from chemotherapy or radiation therapy. Under these conditions, tumor resection with CPB can be achieved with low morbidity and mortality rates. Furthermore, in some cases, especially when ventilatory or hemodynamic instability develops, CPB can be a life-saving procedure that allows complete resection of the thoracic malignancy. CPB should be available in all surgical centers where resection of extensive thoracic malignancies is performed. The long-term survivals reported after these procedures demonstrate that concern about an increased risk of tumor-cell dissemination is unfounded.
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