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Eur J Cardiothorac Surg 2006;29:571-577
© 2006 Elsevier Science NL
Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, 30623 Hannover, Germany
Received 3 August 2005; received in revised form 26 October 2005; accepted 31 October 2005.
* Corresponding author. Present address: Herz-, Thorax-, und herznahe Gefäßchirurgie, Klinikum der Universität Regensburg, Franz-Josef-Strauss-Allee 11, 93055 Regensburg, Germany. Tel.: +49 9406 284535; fax: +49 9406 284400. (Email: KarstenWiebe{at}t-online.de).
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Abstract |
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 Top Abstract 1. Introduction2. Patients and methods3. Results4. DiscussionReferences |
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Key Words: Lung cancer surgery • Pulmonary sarcoma • Cardiopulmonary bypass • Acute lung injury • Inflammatory reactions • Complications
Abbreviations: ALI = acute lung injury • ARDS = acute respiratory distress syndrome • CPB = cardiopulmonary bypass • CT = computed tomography • ECMO = extracorporeal membrane oxygenation • ICU = intensive care unit • LA = left atrium • NMR = magnetic resonance imaging • NYHA = New York Heart Association • OR = operating room • PTFE = polytetrafluoroethylene • POD = postoperative day • RA = right atrium • RV = right ventricle • RVOT = right ventricular outflow tract
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1. Introduction |
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TopAbstract1. Introduction2. Patients and methods3. Results4. DiscussionReferences |
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Due to the rare nature of patients undergoing extended pulmonary resections with the application of CPB for mediastinal involvement, only case reports and recently a few small series had been published [10–12]. Prior reports suggested the technical feasibility and in some of the cases, patients were reported to demonstrate an excellent outcome following complete resection. Some authors advocated the use in lung cancer patients; others restricted the indication. In some reports, palliative indications for relieve of symptoms were included. Appropriate indications for extensive surgical treatment in advanced thoracic tumors invading the heart or great vessels have remained not well defined, especially the roles of neoadjuvant or adjuvant radiation or chemotherapy have not been outlined very well. The aim of this study was to analyze indications, techniques, morbidity, mortality, and long-term results of this radical surgical approach. This series adds a further experience to a rapidly expanding field of interest.
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2. Patients and methods |
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TopAbstract1. Introduction2. Patients and methods3. Results4. DiscussionReferences |
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All patients suspected with primary lung carcinomas underwent cervical mediastinoscopy. Diagnostic bronchoscopy was mandatory. If pneumonectomy was planned, a ventilation and perfusion scan was performed. In selected patients, the maximal oxygen uptake, pulmonary artery pressure, and pulmonary vascular resistance were measured. A coronary angiography was performed in all cases. Patients had to present with acceptable cardiopulmonary function allowing for an extended surgical procedure. Diagnostic procedures comprised computed tomography (CT), magnetic resonance imaging (NMR), transthoracic and transesophageal echocardiography. When indicated endosonography of the esophagus, or cine-NMR of the heart, was included. In addition to the preoperatively planned use, CPB was applied in case of unexpected intraoperative findings (Table 1).
For statistical analysis the SPSS statistical package (SPSS Inc., Chicago) was used. Cumulative survival was calculated by the method of Kaplan–Meier.
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3. Results |
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TopAbstract1. Introduction2. Patients and methods3. Results4. DiscussionReferences |
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In eight patients, a tumor of mesenchymal origin was found (Fig. 1). The diagnoses were leiomyosarcoma (n = 3), rhabdomyosarcoma (n = 2), spindle cell sarcoma (n = 2), and a malignant hemangiopericytoma (n = 1). Three sarcomas were originating from the pulmonary artery. In three patients, the histological diagnosis was non-small cell lung cancer (T4). One patient received neoadjuvant chemotherapy and radiation for downstaging in T4, N2 disease. In one case, the tumor was a metastasis of a rectal cancer that had been completely removed 6 years before in a patient without evidence of other metastasis. In one patient, a large mediastinal mass compressing the heart proved to be a large benign bronchiogenic cyst. Four patients presented with incomplete resections (R1) or abrogated prior procedures in institutions without the availability of CPB. The requirement for CPB was preoperatively planned in 9 of 13 (77%) cases. Extent of the tumor (n = 2), or injury of the common pulmonary artery (n = 2), including a case with the benign cyst, required unexpected application of CPB (Table 1).
The tumors were approached (Table 1) via a median sternotomy (n = 7), postero-lateral thoracotomy (n = 4), or a bilateral clamp-shell incision (n = 2). For arterial canulation, the ascending aorta (n = 9), the descending aorta (n = 1), or the femoral artery (n = 3) were used. Venous access was bicaval (n = 9), femoral (n = 2), or via pulmonary artery (n = 2) canulation. Mean time of operation was 304.6 ± 112.2 min (153–495 min). Time on bypass (Table 2 ) was 140 ± 88 min (24–320 min). In five cases, cardiac arrest was induced by cardioplegia with cross-clamping times of 101 ± 37 min (37–145 min); in another five patients, electrical-induced fibrillation was applied. Lowest rectal temperature was 27 ± 3 °C (20–32 °C). An average of 7 (0–18) units of packed red cells, 5 (0–11) units of fresh frozen plasma, and 0.6 (0–2) units of platelets were administered intraoperatively.
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In the majority of patients, several mediastinal and cardiac structures were affected simultaneously (Table 2). The left atrium was most often invaded by tumor (n = 9), in two cases extending into the pulmonary veins from the opposite side. The common pulmonary artery (n = 7), the right atrium (n = 3), the right ventricle (n = 2), the aorta (n = 1), and the coronary arteries (n = 1) were resected en-bloc with the pulmonary tumor. For reconstruction of cardiac structures, autologous pericardium was used when available (n = 6). In addition, aortic and pulmonary homografts (n = 4) and polytetrafluoroethylene (PTFE) prosthetic material (n = 4) were used. Special emphasis was taken to verify complete resection by intraoperative frozen sections for immediate pathological evaluation. In one patient presenting with non-small cell lung cancer, mediastinal lymph nodes (pN2) infiltrating the trachea prevented complete resection (Table 2). However, resections proved to be complete resections (R0) by pathological examination in 12 of 13 patients (92%).
The 30-day mortality was 15% (2 of 13 patients). One patient died intraoperatively due to right heart failure and pulmonary injury after an excessive time (289 min) on CPB for a complex cardiac reconstruction involving both coronary arteries. Mean time on ventilator in the 12 remaining patients was 30.3 h (3–192 h) (Table 3 ). Three patients required prolonged times (>24 h) of mechanical ventilation due to acute lung injury. One of these patients died due to development of multi-organ failure on day 4. Two patients recovered from respiratory failure. In two cases, postoperative episodes of pneumonia were treated. One of these patients presented with recurrent atelectases. Other complications observed were two re-thoracotomies for a hematothorax. Mean time on ICU was 2.3 days (1–9 days) and mean time in hospital was 19 days (9–40 days) in 11 patients discharged (Table 3).
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At follow-up examinations no local recurrence of tumor at the site of surgery was detected, following complete resection of the malignancy. Cumulative survival rates for all 13 patients were 62% at 1 year and 53% at 3 and 5 years. After a follow-up of 39 months (0–216 months), seven patients were alive (Table 3). Five of the seven survivors were in class NYHA II and two were not limited in their physical activity. Cause of late death (n = 5) was distant metastatic disease in all cases. All three patients presenting with non-small cell lung cancer died at 4, 6, and 16 months, respectively. Mean survival in these patients (n = 3) was only 8.7 ± 3.7 months, compared to 156 ± 35 months in patients (n = 8) with sarcomas. The 1-, 3- and 5-year survival rate was 62.5% in patients presenting with sarcoma, including two perioperative deaths (Fig. 2 ). Five of the six patients discharged were currently alive. Two underwent chemotherapy for late development of a single distant metastasis.
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4. Discussion |
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TopAbstract1. Introduction2. Patients and methods3. Results4. DiscussionReferences |
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In 30.8% of patients, the decision of CPB application was made intraoperatively. In two cases emergent institution of CPB was required for intraoperative injury of the great vessels. Byrne et al. [11] reported 43% of all CPB procedures to be performed for emergency situations. These data underline the importance of CPB availability when advanced thoracic malignancies are surgically approached. It provides a safety net and is helpful when the procedure is more extended than preoperatively expected. In case of suspected tumor invasion of the great vessels of the heart, patients should be directed to a surgical center that is able to provide CP. Four out of 13 patients in our series underwent prior operations in other hospitals that were abrogated due to the unexpected invasion of the heart or great vessels. Park et al. [12] described 3 of 10 patients who underwent CPB-assisted operations following previous unsuccessful attempts of tumor resection.
Often patients will benefit from these radical procedures only if complete microscopic resection can be achieved. We found that 92% of patients had an R0 resection in our series. Comparable results (79–86%) have recently been described [10,11]. Considering the high-risk nature of the performed procedures, a perioperative mortality rate of 15% (2 of 13 patients) is not unexpected. This rate is not different to other series reporting 7% (1 of 14 patients) and 11% (2 of 19 patients), respectively [10,11].
To achieve complete resections, we accepted prolonged times on bypass. This underlines the complexity of the procedures. Compared to other studies published, mean time on bypass (140 min) in our experience was longer compared to other reports (87, 99, and 111 min) [10–12]. Time on cardiopulmonary bypass is known to be a crucial factor for patients’ survival in cardiac surgery, when applied for prolonged periods (>3 h). Beyond 90 min of CPB, an increased pulmonary dysfunction has been observed. However, the application of CPB might cause only minimal detrimental effects, if applied for short periods of time, thus allowing for extended pulmonary resections.
Surgical interventions for advanced thoracic malignancies are associated with a substantial perioperative risk and frequent postoperative pulmonary complications [6]. For standard pneumonectomies, a mortality rate of 5.4% with a morbidity rate of 59% was reported by Algar et al. [13]. In their series of 242 patients undergoing standard pneumonectomies, pulmonary complications were present in 14% of cases. In other reports, the incidence of pulmonary complications following pneumonectomies ranged from 11 to 49%. Extended pneumonectomies and prolonged anesthetic time were associated with the highest rates of pulmonary complications [5,12]. Acute lung injury and acute respiratory distress syndrome represent severe forms of pulmonary failure, which occur in 2.2–4.2% of all pulmonary resections for bronchiogenic cancer and are associated with a mortality rate of 40–72%.
There is considerable evidence that CPB is associated with deterioration of pulmonary function as assessed by measuring the alveolar–arterial oxygenation gradient, intrapulmonary shunt, degree of pulmonary edema, pulmonary compliance, and pulmonary vascular resistance [14]. More frequent and more severe complications with extended periods of mechanical ventilation are expected, if CPB is applied.
In our series, we documented major postoperative pulmonary complications in 5 of 13 patients (38%). One of these patients died intraoperatively due to right heart failure and pulmonary edema after undergoing a complex procedure with prolonged time on CPB. An extended mechanical ventilation period was observed in three patients (>24 h) suffering from acute lung injury. One of these patients progressed and finally died due to the development of multi-organ failure. All other patients recovered from pulmonary dysfunction. The 30-day mortality rate was 15% (2 of 13 patients). Baron et al. [3] reported on four patients presenting with tumor invasion of only the left atrium, who had a short time on CPB (87 ± 25 min), and postoperatively were ventilated for 9.5 h with no major pulmonary complications observed. In contrast, a prolonged ventilatory support (mean of 4.1 days) was described by Vaporciayan et al. [10]. In their study, the hospital mortality was 11% with major complications reported in 58% of patients, including pneumonia (37%) and tracheostomy (16%). Byrne et al. [11] found a mean duration of ventilator support of 2.5 days. One of the 14 patients experienced an acute lung injury, four patients suffered from pneumonia and three underwent tracheostomy.
Bleeding is another frequent complication following CPB-assisted procedures. In a series of lung resection during cardiac operations with CPB, bleeding complications were reported to affect 21% of patients (4 of 19 patients) [15]. In comparison, intervention for a hematothorax following a standard pneumonectomy became necessary only in 4.1% of cases in a report by Alger et al. [13]. In our series, 2 of 13 patients (15%) underwent re-thoracotomy for hematothorax despite perioperative substitution with fresh frozen plasma and platelets. Other recent series reported an incidence of postoperative bleeding complications following lung resections with CPB of 10, 11, and 21%, respectively [10–12].
Extended pneumonectomy with CPB is a rarely performed procedure. Nine patients of our series underwent extended pneumonectomy with CPB for tumor invasion of cardiac structures, compared to four patients, who had a lobectomy. Bacha et al. [16] included four patients with sarcomas in their study but did not differentiate this subgroup to those patients with less extensive pulmonary resections. Vaporciayan et al. [10] reported on 5, Byrne et al. [11] on 10, and Park et al. [12] on 2 extended pneumonectomies. In addition, several case reports had been published in the past [10].
In addition to the difference in the extent of pulmonary resection, the group of patients with pneumonectomies had longer times of operation and longer times on bypass. These intraoperative factors were associated with extended time periods of mechanical ventilation and with higher rates of morbidity and mortality. Only patients undergoing pneumectomies developed serious pulmonary complications.
Significantly higher mortality rates and more frequent pulmonary complications have been reported with pneumonectomy compared to other less extensive pulmonary resections [17–19]. Acute lung injury has been reported to occur twice as often in pneumonectomies as in lobectomies in standard resections [19]. However, there has been no information published on increased complications in extended pneumonectomies with CBP. From our data, we postulate that extended lobectomy with CPB is quite a safe procedure, but pneumonectomy in this setting remains to be associated with life-threatening complications.
Median sternotomy is the most often used approach to combine thoracic and cardiac procedures. For some of the complex cases, we found a clamp-shell incision, as used in pulmonary transplantation, to offer the best exposure. Bicaval venous canulation should be practiced routinely. In case of tumor preventing caval access, femoral vein or pulmonary artery canulation can be alternative ways of connecting the extracorporal bypass.
Dissection of the tumor and the structures involved should be completed as far as possible prior to onset of CPB to minimize the time on CPB. However, if mobile intracardiac tumor or thrombus is present, cardiac arrest or fibrillation should be mandatory prior to tumor mobilization. We prefer moderate hypothermia with 30–34 °C, as deep hypothermia is known to prolong postoperative recovery and cause pulmonary dysfunction. Cardiopulmonary bypass leads to activation of complement, neutrophils, monocytes, macrophages, platelets, and endothelial cells. Suppression of the activation of these inflammatory mediators correlates with a reduction of pulmonary dysfunction [14]. Heparin coating of tubing and oxygenator ameliorates the inflammatory reaction of CPB and reduces the ventilatory requirements following the cardiac surgery [20]. Recently developed minimized CPB units and ECMO systems with modified pumps and less artificial surface are known to reduce the inflammatory effects and cause less pulmonary damage [21]. The inflammatory response can be decreased when blood from the operating field is not recovered directly into the CPB circuit, but a cell-safer device is used. In addition, pharmacological intervention with protease inhibitors or complement inhibition might further reduce the activation of kallekrein, complement, and other systems involved in the inflammatory reaction of CPB. For the future, it can be expected that these technical improvements will enhance the safety of this procedure and reduce the risk of pulmonary complications.
Prognosis in patients with advanced non-small cell lung carcinomas invading the mediastinum is poor. Survival in T4 carcinomas that were resected without CPB has been reported to be 17% after 3 years and 19% after 5 years in another study [22,23]. A hospital mortality rate of 19% and a 5-year survival of 26% in hospital survivors were reported by Pitz et al. [1]. Park et al. [12] argued that it is difficult to justify complex thoracic resections with the potential of prolonged convalescence and substantial morbidity and mortality as long-term survival is limited. However, some patients especially those with N0 disease were reported to have surprisingly long survival rates following complete resection [22]. The indication for CPB-supported surgical treatment in T4 non-small cell lung cancer should be restricted. Such radical surgical therapy may be considered if patients present with N0 disease. The benefit of a neoadjuvant combined chemotherapy and radiation with re-evaluation following induction therapy, which is recommended for patients with advanced non-small cell lung cancer, remains to be investigated in this setting. Radical procedures with CPB in palliative situations, as reported recently, do not seem to be justified [10,11].
In contrast to non-small cell carcinomas, pulmonary sarcomas have a different course of disease and indications for surgical therapy are different. Following the resection of primary pulmonary sarcomas, 5-year survival rates of 48–69% have been reported [16,24,25]. In our series, primary (six) and secondary (two) pulmonary sarcomas invading the lungs and the heart were resected with CPB. The 1-, 3-, and 5-year survival rates were 62.5%, respectively (Fig. 2). These results underline the role of complete surgical resection as a primary goal in the treatment of pulmonary sarcomas. Even advanced sarcomas may have a beneficial long-term outcome. Neoadjuvant chemotherapy should be considered in advanced sarcomas. We found that neoadjuvant chemotherapy in two patients that were unresectable at first presentation allowed for partial response and subsequent complete surgical resection. Porte et al. [25] reported on three patients undergoing preoperative chemotherapy successfully. Currently, there are not enough data to support the routine use of induction therapy [14]. However, adjuvant therapy is indicated in these rare malignancies. The rate of recurrence of pulmonary sarcomas at the primary site or as distant metastasis following resection has been reported to be 36–44% [16,25].
The single-center experience described hereby is limited due to a small number of patients, not allowing for firm statistical evaluation. However, our data support the feasibility of surgical therapy with CPB for pulmonary malignancies invading cardiac structures. We would like to encourage radical resections with support of CPB. Selected patients benefit from radical, complete resections with significantly improved long-term survival rates, especially patients presenting with advanced sarcoma. It may be anticipated that if pulmonary resection is limited to lobectomy and the time of CPB is kept short, no major increase in pulmonary complications will have to be expected. However, extended pneumonectomies with CPB support remain to be associated with a substantial risk of pulmonary complications.
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References |
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TopAbstract1. Introduction2. Patients and methods3. Results4. DiscussionReferences |
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This article has been cited by other articles:
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  M. Zielinski and J. Kuzdzal Pulmonary resections for T4 non-small cell lung cancer with support of cardiopulmonary bypass. Eur. J. Cardiothorac. Surg., October 1, 2006; 30(4): 686 - 686. [Full Text] [PDF]
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K. Wiebe Reply to Zielinski and Kuzdzal. Eur. J. Cardiothorac. Surg., October 1, 2006; 30(4): 686 - 687. [Full Text] [PDF]
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W. Weder Editorial comment Extended pulmonary resections of advanced thoracic malignancies with support of cardio-pulmonary bypass - is surgery justified? Eur. J. Cardiothorac. Surg., April 1, 2006; 29(4): 577 - 578. [Full Text] [PDF]
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