Cancer of the lung is the most common cause of death from cancer in both men and women in the United States. As these cancers grow, they begin to invade local structures, organs, and vessels within the chest. Local progression of disease may occur before metastatic spread and does not necessarily preclude resection. Any contiguous structure in the chest can be involved, although chest wall invasion is the most common, occurring in approximately 5% of patients. Other contiguous intrathoracic structures include the left atrium, aorta, superior vena cava, vertebral bodies, diaphragm, and esophagus. Surgical intervention can achieve local control. Selection of patients may be complex. The potential for complete resection varies widely, and increased morbidity and mortality are well documented for these complex extended resections. The long-term prognosis depends on accurate pretreatment staging to assist in the selection of therapy and complete resection. Cardiopulmonary bypass (CPB) can be a necessary component for surgical resection in certain complex cases. This chapter reviews the role of CPB for the extended resection of lung cancer, as well as the clinical and technical considerations and expected surgical outcomes.

CARDIOPULMONARY BYPASS FOR EXTENDED THORACIC RESECTIONS

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. Mediastinoscopy also must be performed (see Chap. 61).

Most thoracic surgeons are reluctant to perform pulmonary resections with patients on CPB. Several authors^1–4 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. Others^5–7 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 and colleagues reviewed a decade of experience at Brigham and Women's Hospital and Massachusetts General Hospital in Boston.⁵ 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 6 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 and others reported the University of Texas M. D. Anderson Cancer Center experience from January 1995 to July 2000 using CPB for resection of metastatic or noncardiac primary malignancies that extended directly into the heart.⁶ 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.

TECHNICAL CONSIDERATIONS FOR CPB AND RESECTION OF THORACIC TUMORS

The operative approach is based on tumor anatomy, the need for vascular reconstruction, and the urgency with which circulatory support is initiated. To optimize outcomes, one must maintain a flexible strategy with regard to selection of arterial and venous cannulation sites, need for aortic clamping, cardioplegia requirements, and deairing options. When CPB is required in an emergent setting, a thoracotomy is performed, and CPB support may be required to address central injury to a major vascular structure. Byrne and colleagues reported that cannulation after right thoracotomy was consistently achieved via the ascending aorta and right atrium. On the left, cannulation was achieved via the descending thoracic aorta and main pulmonary artery.⁵

If the groin is accessible, systemic venous drainage can be achieved by placing a long venous cannula into the right atrium through the femoral vein. In the emergent setting, decompression of the heart with the ability to control blood loss and return shed blood is usually all that is required to enable primary or patch repair of the injury to the central vascular structure.

In the elective setting, surgical approaches often require the combined expertise of a thoracic surgical oncologist and a cardiac surgeon who is experienced at central vascular reconstruction. Standard ascending aorta and right atrial cannulation is satisfactory to address lesions involving the central pulmonary arterial system. Reconstruction with pulmonary homograft or autologous pericardium can be readily achieved. In lesions involving the left atrium, median sternotomy is usually satisfactory; however, one must be alert to the issues of deairing and ensure appropriate means of preventing systemic air emboli. Additionally, tumor emboli can occur, and care must be taken to limit tumor manipulation before cardiac decompression and adequate circulation control. A well-coordinated combined effort by the general thoracic surgeon, the cardiac surgeon, the anesthesiologist, and the perfusionist is needed to achieve a satisfactory outcome when addressing these complex lesions.

Lung Tumors with Infiltration of the Thoracic Aorta

Left-sided lung cancers may involve the descending thoracic aorta. It is often difficult to determine the presence and extent of aortic invasion on imaging studies (Fig. 70-1). If the fat plane between the aorta and the tumor is absent or there is abutment of the tumor involving greater than 90 degrees of the aortic circumference, invasion should be suspected. However, ultimate determination of involvement of the aorta generally is made at exploration. As with lesions involving the central pulmonary vasculature, these T₄ tumors with full-thickness involvement of the thoracic aorta are classically deemed unresectable. Experience with combined pulmonary and aortic resection is limited and often anecdotal. However, some authors^8–10 have described their experiences with these combined resections. These reviews suggest a favorable impact on survival in highly selected patients; however, the few available reports in the literature make it difficult to draw more generalized conclusions.

TECHNICAL CONSIDERATIONS FOR AORTIC RESECTION AND RECONSTRUCTION

Different technical methods are needed to manage the aorta that is locally invaded with lung cancer. The options include resection of the tumor in a subadventitial plane, partial resection with patch reconstruction, and complete segmental aortic resection with tube graft reconstruction. Nakahara and colleagues reported their results in three patients in whom the aorta was resected at the time of pulmonary resection.¹⁰ One patient was a midterm survivor; however, the other two succumbed to metastatic disease within 1 year. In 1994, Tsuchiya and colleagues reported their experience in 28 patients at the National Cancer Hospital in Tokyo.⁹ Resection in a subadventitial plane was used in 75% of patients. In these 21 patients, 10 had complete resections, and all patients with incomplete resections did poorly. The authors comment that peeling the adventitia off the aorta is inadequate for lung cancer invading the aorta. Of the 7 patients who had a complete aortic resection with tube graft reconstruction, 4 developed recurrent disease. Only 1 of the 7 patients who were managed with complete aortic resection was a long-term survivor. Klepetko and colleagues reported similar observations in their experience in 7 patients undergoing full-thickness aortic resection with patch or tube graft reconstruction.⁸ Perfusion was supported with CPB in 6 of the operations without apparent untoward events. Long-term survival was achieved in 2 of the 7 patients. These observations regarding pulmonary malignancies with direct aortic invasion support the observation that complete resection and long-term cures are rare, but possible, in appropriately selected patients.

VENA CAVA INVOLVEMENT WITH BRONCHOGENIC CARCINOMA

Bronchogenic carcinoma of the right upper lobe can invade the mediastinal pleura and on rare occasions invade the superior vena cava (Fig. 70-2). Involvement of the superior vena cava also may occur as a consequence of metastatic nodal disease, which, when present, is a uniformally poor prognostic factor. There is an increasing experience in extended resections of pulmonary malignancy with en bloc resection of the superior vena cava. Several authors^9–13 have suggested a benefit in selected patients, but there is still uncertainty regarding a consistent benefit. Exacting attention to the technical aspects of venous reconstruction is required to avoid devastating neurologic complications.

Technical Considerations for Vena Cava Resection and Reconstruction

Optimal exposure to the superior vena cava is achieved through median sternotomy. Bronchogenic tumors are approached through the right chest, which provides excellent visualization of the superior vena cava and the atrium but limits access to and control of the left brachiocephalic vein. Two techniques can be used for resection and reconstruction of the superior vena cava. If less than a third of the circumference of the vena cava is involved, partial resection with primary or patch closure using autologous pericardium can be performed if there are concerns regarding stenosis. If there is greater involvement of the superior vena cava, complete resection and reconstruction will be required. Reconstruction can be performed with autogenous venous or prosthetic grafts. Options for autogenous graft replacement include the jugular vein, the superficial femoral vein, or spiral saphenous vein. This option is more limited because the graft diameter must be as great as the brachiocephalic vein for a satisfactory outcome.

Dartevelle has described the use of synthetic polytetrafluoroethylene vascular graft as the material of choice for complete venous replacement.¹¹ Before the work of Dartevelle, prosthetic graft replacement of the superior vena cava was thought to be a surgical contraindication because of the high rate of thrombosis and infection, as well as the deleterious physiologic effects of clamping the superior vena cava. Specific interventions such as maintaining adequate cerebral perfusion pressure, limiting clamp time with efficient reconstruction, paying attention to the prevention of bacterial contamination, using anticoagulation judiciously, and appropriately using shunts or bypass are all required to ensure a satisfactory outcome. Contraindications to superior vena cava resections included complete venous obstruction and involvement by a malignancy that is otherwise unresectable.

Results of Combined Pulmonary and Superior Vena Caval Resection

Dartevelle described his experience with combined pulmonary and complete caval resection in 14 patients with non-small cell lung cancer.¹¹ These extensive tumors required carinal pneumonectomy in 6 patients, extended pneumonectomy in 7 patients, and 1 patient received a lobectomy. Six of the 14 patients had N₂ disease. Major complications were seen in 3 patients and included bronchopleural fistula in 2 and extrapericardial cardiac herniation in 1. The mortality rate was 7.1%, and 5-year survival was 31%.

Thomas and colleagues reviewed their institutional experience in 15 patients, 4 of whom required complete caval resection.¹² There was one postoperative death and a complication rate of 20%. The authors observed a median survival of 8.5 months with two local recurrences, and the 1-, 2-, and 5-year survival rates were 46.7%, 32%, and 24%, respectively. The authors concluded that extended resection, when feasible, is justified.

Spaggiari and colleagues reported similar observations in their report on 25 patients in which 7 patients had complete resection of the superior vena cava with graft interposition.¹³ Ipsilateral mediastinal nodal disease was observed in 56%. Complete resection was achieved in 80% of patients with a perioperative complication rate of 36% and mortality rate of 12%. The observed median survival was 11.5 months, and the 5-year actuarial survival was 29% with 4 long-term survivors. The data were inadequate to differentiate survival according to nodal status, but the authors commented that the survival trends favored node-negative patients. The authors recommended mediastinoscopy in all patients with superior vena cava involvement to exclude N₂ patients.

CHEST WALL INVASION

Primary neoplasms of the lung invade the chest wall in 5% of lung cancers. Pleuritic chest pain is often the presenting symptom and is a predictor of chest wall involvement. Chest wall invasion historically was considered unresectable based on early negative experience.¹⁴ In 1957, Gronquist and colleagues reported a 25% "long term" survival in 16 patients undergoing simultaneous pulmonary and chest wall resection.¹⁵ Multiple subsequent retrospective studies^16–18 demonstrated 5-year survival rates ranging from 22% to 78.5% after complete resection in the absence of nodal metastasis. Subsequent authors (Table 70-1) made similar observations and also demonstrated improvement in the perioperative mortality rate. These observations suggested an improved prognosis in this select group of patients and ultimately led Mountain to redefine stage T₃N₀M₀ lung cancers that invade chest wall as stage IIB, where previously they were classified as stage IIIA.¹⁹

Clinical Evaluation and Considerations

Pleuritic pain occurs in approximately 45% of patients who have chest wall invasion. Despite increasing sophistication of preoperative imaging tests, chest wall invasion cannot be reliably determined. Radiographic evaluation with plain-film images or CT scans does not reliably predict chest wall involvement unless bony invasion or destruction is definitively identified (Fig. 70-3A ). This is seen in approximately 20% of preoperative imaging.²⁰ Bone scan may reveal rib enhancement. PET scanning is not helpful for evaluating chest wall involvement but can provide data regarding possible mediastinal nodal involvement or occult metastatic disease.

As with all patients for whom pulmonary resection is contemplated, an assessment of physiologic reserve for surgery is required in addition to a thorough evaluation and staging for the extent of disease. Respiratory compromise can occur in the perioperative period from changes in chest wall mechanics with potential flail segments, and suspicion should be heightened in patients with minimal pulmonary reserve. This observation has implications regarding the technical considerations for reconstruction.

Technical Considerations and Conduct of Operation

The goals of surgical intervention for lung cancers that invade chest wall are complete en bloc resection adhering to standard thoracic oncologic principles and satisfactory reconstruction of the chest wall for mechanical and cosmetic concerns. Mediastinoscopy must be performed when evaluating patients who have suspected chest wall invasion to rule out the presence of mediastinal nodal disease, which would preclude a curative resection. Studies (see Table 70-1) have consistently demonstrated few, if any, long-term survivals in patients with N₂ disease. The role for neoadjuvant and adjuvant chemotherapy and radiation therapy in these patients is evolving.

If mediastinoscopy is negative, many authors advocate routine thoracoscopic exploration to rule out pleural studding and to assess for resectability, as well as to garner information that would be helpful in the conduct of the procedure.²¹ Regardless of surgical technique, initial exploration of the chest should be performed in an area removed from suspected chest wall involvement. After entering the chest, one should evaluate the hilum to ensure that pulmonary resection is feasible. The mediastinum should be assessed for unsuspected nodal disease. Attention then is directed toward the primary lesion. Firm adherence to the chest wall is indicative of chest invasion across the intrathoracic fascia and necessitates chest wall resection. There is controversy regarding management of tumors that adhere to the parietal pleura. It is clinically challenging to differentiate malignant invasion of the parietal pleura from inflammatory fibrosis. With tumor involving only the parietal pleura, some authors^18,22 have demonstrated comparable long-term patient survival after extrapleural excision versus chest wall excision. However, others^23,24 have observed a higher incidence of histologically positive margins after extrapleural excision and a significant improvement in survival after en bloc resection versus extrapleural excision for these lesions. If there are concerns at the time of surgery regarding parietal pleural invasion, chest wall resection is warranted.

Resection proceeds with detachment of the involved chest wall along with optimally 3- to 5-cm anterior and posterior margins and a rib superior and inferior to the lesion. After chest wall detachment is complete, appropriate anatomic pulmonary resection is performed to achieve en bloc removal of the tumor and maximize the opportunity for complete resection. The location of the chest wall defect then generally will determine the need for reconstruction. Defects deep to the scapula require no reconstruction unless the fifth rib is removed. In such cases, a prosthetic material such as Marlex mesh, Dacron, or Gore-tex should be used to prevent the scapula from catching on the sixth rib. Anterior defects often require a contoured, fixed reconstruction that can be performed with methylmethacrylate between two layers of Marlex mesh (see Fig. 70-3B ). Posteroinferior and lateral defects may be reconstructed adequately with Marlex or Gore-tex that is held taut and sewn to the margins of the chest wall defect. The results from patients undergoing resection of bronchogenic carcinoma with chest wall invasion are listed in Table 70-1 and are discussed above.^25–29

VERTEBRAL BODY INVOLVEMENT

In addition to invading chest wall, bronchogenic tumors also may involve the vertebral bodies. Vertebral body invasion by malignancy classically has been deemed a contraindication to surgical intervention because a cancer-free margin of resection is difficult to ensure and concerns regarding neurologic morbidity from vertebral resection are significant. Advances in spinal instrumentation and reconstruction have enabled some centers to adopt a more aggressive approach to these locally advanced lesions and achieve long-term survival. Preoperatively, CT scanning often can identify vertebral body involvement. MRI can further define the extent of local disease and may be helpful to determine if there is any evidence of spinal cord involvement. If present, involvement of the spinal cord is consistently deemed a definite contraindication because attempts at resection and prognosis are dismal. As with any other locally advanced malignancy, a thorough investigation to rule out nodal or systemic metastasis is required.

Technical Considerations and Results

The technical strategies for resection are varied and include piecemeal resection of the vertebral body versus en bloc partial, hemi-, or total vertebrectomy. Surgical intervention requires the combined expertise of multiple disciplines, including thoracic surgeons, neurosurgeons, and orthopedic surgeons. Reconstruction methods after resection are also varied. The role for preoperative radiotherapy in the management of these lesions is debated.

DeMeester and colleagues reported their experience with resection of lung cancers adherent to the vertebral column in 12 patients.³⁰ They performed tangential resection of the involved vertebral bodies with en bloc pulmonary resection. Eleven patients had negative vertebral body margins, and 1 patient had metastatic mediastinal nodal disease. Reconstruction of the vertebral column was not required. These authors reported an overall 5- and 10-year Kaplan-Meier survival rate of 42% and achieved greater than 5-year survival in 4 patients without any evidence of adverse long-term sequelae. These authors concluded that en bloc resection could provide long-term survival with a good quality of life. Grunenwald and colleagues reported their experience with total vertebrectomy for en bloc resection of tumors invading the spine.³¹ Four patients had lung cancers, and only one was alive and without evidence of disease. Dartevelle's commentary on this report suggested that total vertebral resection was excessive and that the survival results were not encouraging. He reiterated the importance of patient selection, cautioning that further follow-up and greater experience are required for complex resections that involve vertebrae.³¹

Gandhi and colleagues reported the University of Texas M. D. Anderson Cancer Center experience with 17 patients who underwent resection of superior sulcus tumors with involvement of the vertebrae. In this series, 7 patients had total vertebrectomy, 7 had partial vertebrectomy, and 3 were managed with resection of the neural foramina or transverse process.³² Reconstruction of the vertebral column was accomplished with methylmethacrylate, placement of an anterior locking plate and screw construct, and posterior fixation with hooks and rods. The 2-year actuarial survival was 80% for the 11 patients with microscopically negative margins versus 0% for the 6 patients with positive margins. This report reinforced the need for complete surgical resection to achieve a survival benefit.

SUMMARY

The management of bronchogenic carcinomas that invade vital structures within the mediastinum and chest requires sound surgical judgment and a pragmatic approach. Many of these lesions are metastatic at the time of presentation, and a thorough evaluation, including surgical staging of the mediastinum, must be performed to ensure that patients who are offered surgery have a realistic expectation of benefit. Since the majority of data regarding these subgroups of patients are case series and anecdotal reports, conclusions are difficult to draw. However, resections and the appropriate use of CPB to provide a margin of safety for these extended operations do offer a potential for curative therapy in an appropriately selected patient. Prognosis for these patients is otherwise dismal.

EDITOR'S COMMENT

The authors have done an excellent job of reviewing the various types of extended resection of lung cancers. It is my general view that en bloc resection of the chest wall, axial skeleton, and major veins is acceptable. Extended PA resection with angioplasty reconstruction also is a reasonable option for lung cancer patients. On the other hand, I have not been in favor of major systemic artery resection including the aorta or major head vessels, given their propensity for distant metastatic spread. In addition, cardiopulmonary bypass backup for central tumors that may require a repair of the main PA or PV at the atrial cuff is also occasionally warranted.

–MJK

REFERENCES