Superior Vena Ca val R e s e c t i o n i n Lu n g Ca n c e r Dong-Seok D. Lee, MD*, Raja M. Flores, MD KEYWORDS Lung cancer Superior vena cava Caval invasion Caval resection Caval reconstruction
KEY POINTS Superior vena caval (SVC) invasion has been downstaged to reflect potential resectability with the most recent staging classification. Patterns of involvement include central tumor or metastatic mediastinal lymph nodes. En bloc resection may require tangential or complete SVC resection. Reconstruction may entail simple suture repair or a prosthesis. Five-year survival rates can reach up to 30%.
Lung cancer is the leading cause of cancer death worldwide. Surgical resection remains the mainstay of treatment of early-stage disease. Involvement of the superior vena cava (SVC) in lung carcinoma has traditionally been considered a contraindication for surgical resection. These patients have historically been classified as stage IIIB disease, with a 5-year survival of up to 8%.1
BACKGROUND Over the past 30 years, reports in the literature have challenged this notion. Patients undergoing SVC resection with reconstruction in the setting of lung cancer have reported 5-year survival rates up to 30% (Table 1). Therefore, the most recent iteration of the staging system has taken this into account and has transferred T4N0–1M0 tumors into stage IIIA disease. Superior vena cava involvement encompasses a spectrum of diseases. The SVC can be involved through either direct invasion of central tumors (T4 disease) or invasion of metastatic lymph nodes
(N2 disease). In addition, it can be involved in isolation or in conjunction with other mediastinal structures. Patients may present with SVC syndrome.
PREOPERATIVE EVALUATION Comprehensive preoperative evaluation is imperative in determining whether a patient is an appropriate surgical candidate. A concerted effort should be made to determine whether N2 disease is present through diagnostic imaging and possibly diagnostic biopsies. Sites of distant disease preclude surgical resection. Preoperative pulmonary function testing is essential, because resection may necessitate pneumonectomy. In addition, the phrenic nerve is often sacrificed with complete SVC resection; thus, bilateral phrenic nerve involvement is a contraindication to resection.
THERAPEUTIC OPTIONS AND/OR SURGICAL TECHNIQUES The surgical approach is based on surgeon preference. Most resections can be performed via a standard posterolateral thoracotomy, but other
Disclosure: Neither author has any conflicts of interest to disclose. Department of Thoracic Surgery, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1023, New York, NY 10029, USA * Corresponding author. E-mail address: [email protected] Thorac Surg Clin 24 (2014) 441–447 http://dx.doi.org/10.1016/j.thorsurg.2014.07.009 1547-4127/14/$ – see front matter Published by Elsevier Inc.
thoracic.theclinics.com
INTRODUCTION
442
Table 1 Results of SVC resection and reconstruction in the setting of lung cancer from selected case series
Author
Patients
Lanuti et al,8 2009 Suzuki et al,7 2004 Shargall et al,6 2004 Sekine et al,9 2010 Thomas et al,10 1994 Yildizeli et al,5 2008 Misthos et al,11 2007 Spaggiari et al,12 2004
9 40 15 9 15 39 9 109
Morbidity (%) 40.0
20.0 10.3 30.0
Mortality (%)
Median Survival
5-Year Survival (%)
21.4 mo
31.0 24.0 57.0 (3-y) 18.8 24.0 29.4 11.0 21.0
10.0 14.0
40.0 mo
7.0 7.7 0 12.0
8.5 mo 19.0 mo 31.0 mo 11.0 mo
Fig. 1. A partial occlusion clamp is placed over a small tumor invading the SVC for vascular control. (From Garcia A, Flores RM. Surgical management of tumors invading the superior vena cava. Ann Thorac Surg 2008;85:2144; with permission.)
Superior Vena Caval Resection in Lung Cancer approaches include median sternotomy, hemiclamshell thoracotomy, cervicosternotomy, and combined cervicotomy and thoracotomy. Large-bore intravenous access in the lower extremity is necessary to maintain volume during SVC clamping. Superior vena caval resection and reconstruction can be performed through tangential or complete resection. When only a small portion of the SVC is involved, a partial occlusion clamp can be used for vascular control with subsequent en bloc resection. Depending on the size of the defect, a primary suture repair can be attempted or patch repair can be performed with autologous pericardium or prosthesis (Figs. 1 and 2). This
technique avoids the risk of potential future graft infection. If more than 50% of the diameter of the SVC requires resection, a graft replacement becomes necessary. In the case of complete resection, total SVC clamping is necessary for vascular control. Attempts should be made to clamp the SVC above the azygos vein to preserve some flow to limit brain anoxia. However, if tumor anatomy makes this impossible, the SVC can be clamped for up to 60 minutes based on experimental animal models.2 Patients with extensive collateralization of flow from chronic SVC syndrome have few hemodynamic sequelae from cross-clamping. However,
Fig. 2. Patch repair of SVC wall with autologous pericardium. (From Garcia A, Flores RM. Surgical management of tumors invading the superior vena cava. Ann Thorac Surg 2008;85:2144; with permission.)
443
444
Lee & Flores
Fig. 3. Hemodynamic changes during cross-clamping of the SVC. (From Dartevelle P, Macchiarini P, Chapelier A. Technique of superior vena cava resection and reconstruction. Chest Surg Clin North Am 1995;5:350; with permission.)
acute occlusion of the patent SVC with a clamp can induce several adverse hemodynamic effects. Decreased right ventricular preload results in decreased cardiac output and eventual systemic hypotension. In addition, increased venous pressure can increase the risk of intracranial thrombosis and edema. This combination can result in irreversible brain damage. Therefore, given these potential hemodynamic effects, patients presenting with acute SVC obstruction should never be considered for urgent SVC resection. These hemodynamic effects are usually self-limiting and can be minimized intraoperatively with intravascular fluid expansion and vasoconstrictive agents (Fig. 3).3 Complete SVC resection and reconstruction can be performed with an in situ interposition graft using a ringed polytetrafluoroethylene graft or tubularized pericardium with or without a caval shunt after resection (Figs. 4 and 5). For tumors involving
Fig. 4. Resection of the SVC with graft interposition using a ringed polytetrafluoroethylene graft. (From Garcia A, Flores RM. Surgical management of tumors invading the superior vena cava. Ann Thorac Surg 2008;85:2145; with permission.)
Superior Vena Caval Resection in Lung Cancer
Fig. 5. A graft is sewn from the right atrium to the left innominate vein before tumor resection. SVC, superior vena cava. (From Garcia A, Flores RM. Surgical management of tumors invading the superior vena cava. Ann Thorac Surg 2008;85:2145; with permission.)
the proximal SVC and the right innominate vein, the graft may be placed between the left innominate vein and the right atrium, followed by SVC resection. Only one innominate venous drainage needs to be preserved, because the unilateral arm swelling seen with transection of one vein resolves over time. Systemic heparinization is sometimes recommended, but the authors do not
routinely heparinize. Cardiopulmonary bypass is usually not necessary.
COMPLICATIONS AND CONCERNS Postoperative morbidity and mortality can be as high as 40% and 14%, respectively. Most complications are respiratory. Incidence of graft
445
446
Lee & Flores infection can be as high as 7% but occur exclusively secondary to pulmonary infectious complications (bronchopleural fistula, empyema, lung abscess). Induction therapy is associated with a statistically significant increased risk of postoperative complications. Greater extent of pulmonary resection shows a trend toward an increased risk of mortality but does not reach statistical significance.4 Early graft thrombosis (within 1 month) has been reported to be as high as 11%. Late graft thrombosis has been reported as high as 30%. Risk of thrombosis may be related to SVC stenosis in primary repairs, competitive flow from extra grafts or extensive collaterals, or graft caliber. Postoperative anticoagulation with oral warfarin for 3 to 6 months is often given.
CLINICAL OUTCOMES Long-term outcomes of SVC resection and reconstruction in the setting of advanced lung cancer yields median survival ranging from 8.5 to 40.0 months, with a 5-year survival rate up to 30%. Patients with N2 disease show a trend toward worse survival outcomes than those with N0/N1 disease, which does not reach statistical significance (Fig. 6). Lesser extent of pulmonary resection (lobectomy vs pneumonectomy vs carinal pneumonectomy) also improves long-term outcomes.5 Although induction therapy was
Fig. 6. Survival curves (actuarial method) of patients with N0–1 lymph node involvement (continuous curve) or N2 involvement (dotted curve) and SVC system resection for T4, non-small cell lung cancer. The numbers along the curves indicate the patients alive and still at risk at the corresponding date. The 5-year probabilities of survival were 30% and 25%, respectively. The comparison by log-rank test was not significant. (From Spaggiari L, Regnard JF, Magdeleinat P, et al. Extended resections for bronchogenic carcinoma invading the superior vena cava system. Ann Thorac Surg 2000;69:235; with permission.)
associated with increased perioperative morbidity, it also tends to increase disease-free survival.6 In addition, improved survival was seen with SVC invasion from primary tumor rather than metastatic mediastinal nodes (5-year survival rates of 36.0% vs 6.6%).7
SUMMARY Lung cancer with involvement of the SVC is uncommon but presents a unique management challenge. Discovery of N2 disease should be given its due diligence and these patients should undergo induction therapy. Patients can attain favorable long-term outcomes with surgery, but they need to be carefully selected at specialized centers.
REFERENCES 1. Tanoue LT, Detterbeck FC. New TNM classification for non-small-cell lung cancer. Expert Rev Anticancer Ther 2009;9:413–23. 2. Masuda H, Ogata T, Kikuchi K. Physiologic changes during temporary occlusion of the superior vena cava in cynomolgus monkeys. Ann Thorac Surg 1989;47:890–6. 3. Dartevelle PG. Extended operations for the treatment of lung cancer. Ann Thorac Surg 1997;63:12–9. 4. Spaggiari L, Thomas P, Magdeleinat P, et al. Superior vena cava resection with prosthetic replacement for non-small cell lung cancer: long term results of a multicentric study. Eur J Cardiothorac Surg 2002;21: 1080–6. 5. Yildizeli B, Dartevelle PG, Fadel E, et al. Results of primary surgery with T4 non-small cell lung cancer during a 25-year period in a single center: the benefit is worth the risk. Ann Thorac Surg 2008;86: 1065–75. 6. Shargall Y, de Perrot M, Keshavjee S, et al. 15 years single center experience with surgical resection of the superior vena cava for non-small cell lung cancer. Lung Cancer 2004;45:357–63. 7. Suzuki K, Asamura H, Watanabe S, et al. Combined resection of superior vena cava for lung carcinoma: prognostic significance of patterns of superior vena cava invasion. Ann Thorac Surg 2004;78:1184–9. 8. Lanuti M, De Delva PE, Gaissert HA, et al. Review of superior vena cava resection in the management of benign disease and pulmonary or mediastinal malignancies. Ann Thorac Surg 2009;88:392–8. 9. Sekine Y, Suzuki H, Saitoh Y, et al. Prosthetic reconstruction of the superior vena cava for malignant disease: surgical techniques and outcomes. Ann Thorac Surg 2010;90:223–8. 10. Thomas P, Magnan PE, Moulin G, et al. Extended operation for lung cancer invading the superior vena cava. Eur J Cardiothorac Surg 1994;8:177–82.
Superior Vena Caval Resection in Lung Cancer 11. Misthos P, Papagiannakis G, Kokotsakis J, et al. Surgical management of lung cancer invading the aorta or the superior vena cava. Lung Cancer 2007;56: 223–7.
12. Spaggiari L, Magdeleinat P, Kondo H, et al. Results of superior vena cava resection for lung cancer: analysis of prognostic factors. Lung Cancer 2004; 44:339–46.
447
KEY POINTS Superior vena caval (SVC) invasion has been downstaged to reflect potential resectability with the most recent staging classification. Patterns of involvement include central tumor or metastatic mediastinal lymph nodes. En bloc resection may require tangential or complete SVC resection. Reconstruction may entail simple suture repair or a prosthesis. Five-year survival rates can reach up to 30%.
Lung cancer is the leading cause of cancer death worldwide. Surgical resection remains the mainstay of treatment of early-stage disease. Involvement of the superior vena cava (SVC) in lung carcinoma has traditionally been considered a contraindication for surgical resection. These patients have historically been classified as stage IIIB disease, with a 5-year survival of up to 8%.1
BACKGROUND Over the past 30 years, reports in the literature have challenged this notion. Patients undergoing SVC resection with reconstruction in the setting of lung cancer have reported 5-year survival rates up to 30% (Table 1). Therefore, the most recent iteration of the staging system has taken this into account and has transferred T4N0–1M0 tumors into stage IIIA disease. Superior vena cava involvement encompasses a spectrum of diseases. The SVC can be involved through either direct invasion of central tumors (T4 disease) or invasion of metastatic lymph nodes
(N2 disease). In addition, it can be involved in isolation or in conjunction with other mediastinal structures. Patients may present with SVC syndrome.
PREOPERATIVE EVALUATION Comprehensive preoperative evaluation is imperative in determining whether a patient is an appropriate surgical candidate. A concerted effort should be made to determine whether N2 disease is present through diagnostic imaging and possibly diagnostic biopsies. Sites of distant disease preclude surgical resection. Preoperative pulmonary function testing is essential, because resection may necessitate pneumonectomy. In addition, the phrenic nerve is often sacrificed with complete SVC resection; thus, bilateral phrenic nerve involvement is a contraindication to resection.
THERAPEUTIC OPTIONS AND/OR SURGICAL TECHNIQUES The surgical approach is based on surgeon preference. Most resections can be performed via a standard posterolateral thoracotomy, but other
Disclosure: Neither author has any conflicts of interest to disclose. Department of Thoracic Surgery, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1023, New York, NY 10029, USA * Corresponding author. E-mail address: [email protected] Thorac Surg Clin 24 (2014) 441–447 http://dx.doi.org/10.1016/j.thorsurg.2014.07.009 1547-4127/14/$ – see front matter Published by Elsevier Inc.
thoracic.theclinics.com
INTRODUCTION
442
Table 1 Results of SVC resection and reconstruction in the setting of lung cancer from selected case series
Author
Patients
Lanuti et al,8 2009 Suzuki et al,7 2004 Shargall et al,6 2004 Sekine et al,9 2010 Thomas et al,10 1994 Yildizeli et al,5 2008 Misthos et al,11 2007 Spaggiari et al,12 2004
9 40 15 9 15 39 9 109
Morbidity (%) 40.0
20.0 10.3 30.0
Mortality (%)
Median Survival
5-Year Survival (%)
21.4 mo
31.0 24.0 57.0 (3-y) 18.8 24.0 29.4 11.0 21.0
10.0 14.0
40.0 mo
7.0 7.7 0 12.0
8.5 mo 19.0 mo 31.0 mo 11.0 mo
Fig. 1. A partial occlusion clamp is placed over a small tumor invading the SVC for vascular control. (From Garcia A, Flores RM. Surgical management of tumors invading the superior vena cava. Ann Thorac Surg 2008;85:2144; with permission.)
Superior Vena Caval Resection in Lung Cancer approaches include median sternotomy, hemiclamshell thoracotomy, cervicosternotomy, and combined cervicotomy and thoracotomy. Large-bore intravenous access in the lower extremity is necessary to maintain volume during SVC clamping. Superior vena caval resection and reconstruction can be performed through tangential or complete resection. When only a small portion of the SVC is involved, a partial occlusion clamp can be used for vascular control with subsequent en bloc resection. Depending on the size of the defect, a primary suture repair can be attempted or patch repair can be performed with autologous pericardium or prosthesis (Figs. 1 and 2). This
technique avoids the risk of potential future graft infection. If more than 50% of the diameter of the SVC requires resection, a graft replacement becomes necessary. In the case of complete resection, total SVC clamping is necessary for vascular control. Attempts should be made to clamp the SVC above the azygos vein to preserve some flow to limit brain anoxia. However, if tumor anatomy makes this impossible, the SVC can be clamped for up to 60 minutes based on experimental animal models.2 Patients with extensive collateralization of flow from chronic SVC syndrome have few hemodynamic sequelae from cross-clamping. However,
Fig. 2. Patch repair of SVC wall with autologous pericardium. (From Garcia A, Flores RM. Surgical management of tumors invading the superior vena cava. Ann Thorac Surg 2008;85:2144; with permission.)
443
444
Lee & Flores
Fig. 3. Hemodynamic changes during cross-clamping of the SVC. (From Dartevelle P, Macchiarini P, Chapelier A. Technique of superior vena cava resection and reconstruction. Chest Surg Clin North Am 1995;5:350; with permission.)
acute occlusion of the patent SVC with a clamp can induce several adverse hemodynamic effects. Decreased right ventricular preload results in decreased cardiac output and eventual systemic hypotension. In addition, increased venous pressure can increase the risk of intracranial thrombosis and edema. This combination can result in irreversible brain damage. Therefore, given these potential hemodynamic effects, patients presenting with acute SVC obstruction should never be considered for urgent SVC resection. These hemodynamic effects are usually self-limiting and can be minimized intraoperatively with intravascular fluid expansion and vasoconstrictive agents (Fig. 3).3 Complete SVC resection and reconstruction can be performed with an in situ interposition graft using a ringed polytetrafluoroethylene graft or tubularized pericardium with or without a caval shunt after resection (Figs. 4 and 5). For tumors involving
Fig. 4. Resection of the SVC with graft interposition using a ringed polytetrafluoroethylene graft. (From Garcia A, Flores RM. Surgical management of tumors invading the superior vena cava. Ann Thorac Surg 2008;85:2145; with permission.)
Superior Vena Caval Resection in Lung Cancer
Fig. 5. A graft is sewn from the right atrium to the left innominate vein before tumor resection. SVC, superior vena cava. (From Garcia A, Flores RM. Surgical management of tumors invading the superior vena cava. Ann Thorac Surg 2008;85:2145; with permission.)
the proximal SVC and the right innominate vein, the graft may be placed between the left innominate vein and the right atrium, followed by SVC resection. Only one innominate venous drainage needs to be preserved, because the unilateral arm swelling seen with transection of one vein resolves over time. Systemic heparinization is sometimes recommended, but the authors do not
routinely heparinize. Cardiopulmonary bypass is usually not necessary.
COMPLICATIONS AND CONCERNS Postoperative morbidity and mortality can be as high as 40% and 14%, respectively. Most complications are respiratory. Incidence of graft
445
446
Lee & Flores infection can be as high as 7% but occur exclusively secondary to pulmonary infectious complications (bronchopleural fistula, empyema, lung abscess). Induction therapy is associated with a statistically significant increased risk of postoperative complications. Greater extent of pulmonary resection shows a trend toward an increased risk of mortality but does not reach statistical significance.4 Early graft thrombosis (within 1 month) has been reported to be as high as 11%. Late graft thrombosis has been reported as high as 30%. Risk of thrombosis may be related to SVC stenosis in primary repairs, competitive flow from extra grafts or extensive collaterals, or graft caliber. Postoperative anticoagulation with oral warfarin for 3 to 6 months is often given.
CLINICAL OUTCOMES Long-term outcomes of SVC resection and reconstruction in the setting of advanced lung cancer yields median survival ranging from 8.5 to 40.0 months, with a 5-year survival rate up to 30%. Patients with N2 disease show a trend toward worse survival outcomes than those with N0/N1 disease, which does not reach statistical significance (Fig. 6). Lesser extent of pulmonary resection (lobectomy vs pneumonectomy vs carinal pneumonectomy) also improves long-term outcomes.5 Although induction therapy was
Fig. 6. Survival curves (actuarial method) of patients with N0–1 lymph node involvement (continuous curve) or N2 involvement (dotted curve) and SVC system resection for T4, non-small cell lung cancer. The numbers along the curves indicate the patients alive and still at risk at the corresponding date. The 5-year probabilities of survival were 30% and 25%, respectively. The comparison by log-rank test was not significant. (From Spaggiari L, Regnard JF, Magdeleinat P, et al. Extended resections for bronchogenic carcinoma invading the superior vena cava system. Ann Thorac Surg 2000;69:235; with permission.)
associated with increased perioperative morbidity, it also tends to increase disease-free survival.6 In addition, improved survival was seen with SVC invasion from primary tumor rather than metastatic mediastinal nodes (5-year survival rates of 36.0% vs 6.6%).7
SUMMARY Lung cancer with involvement of the SVC is uncommon but presents a unique management challenge. Discovery of N2 disease should be given its due diligence and these patients should undergo induction therapy. Patients can attain favorable long-term outcomes with surgery, but they need to be carefully selected at specialized centers.
REFERENCES 1. Tanoue LT, Detterbeck FC. New TNM classification for non-small-cell lung cancer. Expert Rev Anticancer Ther 2009;9:413–23. 2. Masuda H, Ogata T, Kikuchi K. Physiologic changes during temporary occlusion of the superior vena cava in cynomolgus monkeys. Ann Thorac Surg 1989;47:890–6. 3. Dartevelle PG. Extended operations for the treatment of lung cancer. Ann Thorac Surg 1997;63:12–9. 4. Spaggiari L, Thomas P, Magdeleinat P, et al. Superior vena cava resection with prosthetic replacement for non-small cell lung cancer: long term results of a multicentric study. Eur J Cardiothorac Surg 2002;21: 1080–6. 5. Yildizeli B, Dartevelle PG, Fadel E, et al. Results of primary surgery with T4 non-small cell lung cancer during a 25-year period in a single center: the benefit is worth the risk. Ann Thorac Surg 2008;86: 1065–75. 6. Shargall Y, de Perrot M, Keshavjee S, et al. 15 years single center experience with surgical resection of the superior vena cava for non-small cell lung cancer. Lung Cancer 2004;45:357–63. 7. Suzuki K, Asamura H, Watanabe S, et al. Combined resection of superior vena cava for lung carcinoma: prognostic significance of patterns of superior vena cava invasion. Ann Thorac Surg 2004;78:1184–9. 8. Lanuti M, De Delva PE, Gaissert HA, et al. Review of superior vena cava resection in the management of benign disease and pulmonary or mediastinal malignancies. Ann Thorac Surg 2009;88:392–8. 9. Sekine Y, Suzuki H, Saitoh Y, et al. Prosthetic reconstruction of the superior vena cava for malignant disease: surgical techniques and outcomes. Ann Thorac Surg 2010;90:223–8. 10. Thomas P, Magnan PE, Moulin G, et al. Extended operation for lung cancer invading the superior vena cava. Eur J Cardiothorac Surg 1994;8:177–82.
Superior Vena Caval Resection in Lung Cancer 11. Misthos P, Papagiannakis G, Kokotsakis J, et al. Surgical management of lung cancer invading the aorta or the superior vena cava. Lung Cancer 2007;56: 223–7.
12. Spaggiari L, Magdeleinat P, Kondo H, et al. Results of superior vena cava resection for lung cancer: analysis of prognostic factors. Lung Cancer 2004; 44:339–46.
447
