Cancer progression is a multistep process including proliferation, migration, vascular invasion, and angiogenesis. The effects of operative stress on cancer cell proliferation have been shown in several in vitro models.6–8 One such study demonstrated that lung cancer cell proliferation was better in human serum obtained immediately following lung resection when compared with serum drawn preoperatively.8
The immunosuppressive effects of extracorporeal circulation have been clearly elucidated. The physiologic stress of CPB has been shown to alter the circulating levels of certain cytokines and growth factors.9–11 There are also inhibitory effects to both cell-mediated and humoral immunity.12,13 In a study performed in patients undergoing cardiac surgery with and without CPB, those undergoing CPB had a significantly decreased inhibitory capacity of serum for cancer cell proliferation.14 Previous series of extended resections have demonstrated an earlier recurrence rate after resection with CPB.3,15
Centrally Advanced Tumors
Locally advanced tumors that involve the central pulmonary vasculature or the heart (T4 lesions) are classically considered to be unresectable. Achieving a tumor-free proximal margin or satisfactory proximal vascular control may not be possible with standard (non-CBP) techniques. A small but definable subset of such patients will benefit from surgery if CPB is used to facilitate these complex resections. Accurate preoperative evaluation, including aggressive staging, must be performed to exclude the presence of occult metastatic disease, determine the patient's physiologic fitness, and establish the limits of resection to achieve the optimal long-term survival for each individual patient. Since these tumors are often larger and more centrally located, preoperative imaging should include PET and CT scanning. There should be consideration for magnetic resonance imaging (MRI) of the brain to rule out occult disease. Mediastinoscopy must be performed not only for identifying nodal disease, but also as an assessment of the extent of airway and pulmonary artery involvement.
The role of induction chemotherapy prior to resection of T4 malignancies remains undefined. There are some small series in which preoperative chemotherapy improved resectability.16–18 In one series, induction chemotherapy prevented 20% of patients from proceeding on to resection due to toxic side effects.19 Furthermore, there is evidence that induction therapy increases surgical morbidity and mortality.20–22 In patients undergoing extended surgical resection, induction therapy followed by surgery is associated with an increase in morbidity and mortality when compared to surgery alone.20 Therefore, decisions for preoperative chemotherapy should be tailored on a case-by-case basis.
Most thoracic surgeons are reluctant to perform pulmonary resections with patients on CPB. Several authors23–26 have reviewed the results and safety of combined cardiac and pulmonary procedures requiring CPB. Their opinions are varied, and several authors have expressed concerns for the adverse effects of CPB on hemostasis and pulmonary function. Others4,27,28 with significant institutional experience have written more extensively on the subject, describing the advantages, disadvantages, and parameters for patient selection when CPB is used as an adjunct to conventional thoracic surgical techniques.
Byrne et al.4 reviewed a decade of experience at Brigham and Women's Hospital and Massachusetts General Hospital in Boston. Between January 1992 and September 2002, CPB was used in 14 patients during planned curative resection of locally advanced thoracic malignancies. In 8 of the 14 patients, CPB use was planned to facilitate resection. In the remaining six patients, CPB was required as an emergent therapy to manage central vascular injury. Indications for planned CPB included tumor involvement of the left atrium, pulmonary artery, and superior vena cava. Complete resection was achieved in 12 patients (86%). There was one operative death from pulmonary embolism. Complications included low cardiac output state (5), stroke (1), pulmonary edema (1), and reoperation for bleeding (3). The overall 1-, 3-, and 5-year survival rates were 57%, 36%, and 21%, respectively. The authors concluded that although CPB is rarely required for thoracic malignancy resection, in appropriate circumstances, it can be used with low morbidity and mortality and may be lifesaving if the surgery is complicated by a central vascular injury. They also concluded that the ability to perform a complete resection influences ultimate survival. In addition, optimal outcome depends on careful patient selection with use of radiographic imaging and thorough intraoperative inspection.
Vaporciyan et al.28 reported the University of Texas MD Anderson Cancer Center's experience from January 1995 to July 2000 using CPB for resection of metastatic or noncardiac primary malignancies that extended directly into the heart. This series included 19 patients, 11 of whom underwent surgery for curative intent. Complete resection was achieved in 10 of these patients. There were two deaths in the group operated on for palliation. Major complications occurred in the majority of patients (58%) and included acute respiratory distress syndrome, mediastinal hematoma, and pneumonia. The overall 1- and 2-year survival rates were 65% and 45%, respectively. The authors concluded that the use of CPB has a role in selected patients with these central thoracic malignancies if there is confidence that complete resection can be achieved.