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The early and late results of combined off-pump coronary artery bypass grafting and pulmonary resection in patients with concomitant lung cancer and unstable coronary heart disease

Wojciech Dyszkiewicz^_*, Marek Jemielity, Cezary Piwkowski, Mariusz Kasprzyk, Bartomiej Perek, Lukasz Gasiorowski, Elbieta Kaczmarek

Department of Thoracic Surgery, Karol Marcinkowski University of Medical Sciences, 62 Szamarzewski St., 60-569 Poznan, Poland

Received 16 January 2008; received in revised form 9 May 2008; accepted 19 May 2008.

^_* Corresponding author. Tel.: +48 61 66 54 349; fax: +48 61 66 54 353. (Email: dyszkiewicz{at}wp.pl).

	Abstract

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 
Objective: The aim of this study was to analyze the early and long-term results of simultaneous surgical treatment of both coronary heart disease (CHD) and lung cancer. Methods: Twenty-five patients with the diagnoses of both non-small cell lung cancer (NSCLC) and unstable angina were operated on between 2001 and 2006 in the Department of Cardiothoracic Surgery at the University of Medical Sciences in Pozna, Poland. Myocardial revascularization was performed simultaneously with the lung resection. The mean patient age was 63 years. The majority (18 patients) were male and the stage of lung cancer was predominantly AJCC II. Most of the patients were classified as stage II or III CCS and the predominant pathology was a two-vessel disease. Fifteen lobectomies, six pneumonectomies and four wedge resections were performed together with the aortocoronary graft implantation (mean: 1.9 graft per patient). Results: There were no postoperative deaths or perioperative myocardial infarctions (MI). The most frequent complications were as follows: atrial fibrillation (24%), atelectasis (12%) and residual pneumothorax (12%). All the patients were followed up for 8–60 months. Within this period, eight patients (32%) died, mostly due to the cancer relapse. The local recurrence of lung cancer and distant metastases were the only factors statistically influencing the late survival. No patient in the entire follow-up period had a MI. In three patients, the symptoms of recurrent angina occurred and one of them underwent a coronary stent implantation. Conclusions: Simultaneous off-pump myocardial revascularization and lung resection is a safe and effective treatment when unstable CHD and lung cancer coexist. In selected patients, this combined procedure may be an alternative to the two-stage approach, surgical or non-surgical (cardiologic) interventions preceding the pulmonary resection. The only statistically significant factor having an impact on long-term survival is the recurrence of the cancer.

Key Words: Lung cancer • Off-pump CABG • Concomitant cardiothoracic operations

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 
Coronary heart disease (CHD) carries a significant impact on the surgical morbidity of lung cancer patients [1–3]. Although the percentage of patients affected by both diseases reported by cardiac surgeons is relatively small (0.5%) [4–6], it is definitely underestimated as the figures reported are only incidental findings relating to patients qualified for cardiosurgical procedures. On the other hand, from the thoracic surgery center standpoint, at least 5% of patients awaiting a major lung resection require preoperative cardiologic or surgical interventions [7]. These interventions, especially in patients with an unstable CHD, or after a recent myocardial infarction (MI), require a good standard of care in this high-risk group in order to reduce surgical morbidity and mortality after thoracic surgery. Although there is no controversy as to whether these cardiac procedures should be done or not, it is still unclear which therapeutic option is the most beneficial. Currently, three options are available. The first is coronary angioplasty and/or stent placement before the lung resection. The second option is coronary artery bypass grafting (CABG) followed by lung resection and the third is simultaneous CABG and lung resection. There is a divergence of opinion about the timing and sequencing of these procedures. In our study, we decided to present the results of simultaneous off-pump myocardial revascularization combined with a major lung resection due to lung cancer.

The aim of this study was to analyze the early and long-term results of simultaneous surgical treatment of both CHD and lung cancer. The study group consisted only of those patients in whom cardiologic intervention was either not feasible or had previously failed.

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 
Twenty-five patients with the diagnoses of both non-small cell lung cancer (NSCLC) and unstable angina were operated on between 2001 and 2006 in the Department of Cardiothoracic Surgery at the University of Medical Sciences in Pozna, Poland. Myocardial revascularization was performed simultaneously with the lung resection. The mean patient age was 63 years (57–75 SD ± 12). The majority (18 patients) were male and the stage of lung cancer was predominantly AJCC II (18 patients). The most frequent pathology was squamous cell carcinoma (56%). Almost half of the operated patients had a history of myocardial infarction and the entire population of patients required the daily use of nitrates or beta blocking agents related to the symptomatic angina. Thirteen (52%) patients had undergone either coronary angioplasty and/or stenting before the lung cancer had been diagnosed. The majority of the patients had a two-vessel disease at stages II or III CCS. The most common underlying conditions were arterial hypertension, COPD, diabetes, and peripheral arterial disease. A summary of the clinical data is presented in Table 1 . Apart from a routine clinical examination and blood serum analysis the following tests were routinely performed: bronchoscopy, chest CT, abdominal ultrasound, cardiac echocardiography and coronarography. Patients with enlargement of the mediastinal lymph nodes, detected on the chest CT, underwent a staging mediastinoscopy. Those with a positive N2 disease were excluded from the study. In conclusion, the study group consisted only of those patients in whom either previous cardiologic interventions had not been feasible or had failed, and who had both symptomatic angina and resectable lung cancer.

A median sternotomy approach was employed for 20 of the patients. In four patients the preferred procedure was a left lateral thoracotomy and for one a sternotomy and partial left thoracotomy was used. In the first stage of the operation, coronary anastomoses were performed on the beating heart (off-pump CABG), followed by the pulmonary resection. In two cases, the lung resection preceded the revascularization (a wedge resection in one patient and a lobectomy in one other). During these procedures there was no need for cardio-pulmonary bypass (CPB standby) or cardioplegia-induced cardiac arrest. The average number of anastomosed coronary vessels was 1.9. In more than 1/3 of the anastomoses the mammary or radial arteries were used as free grafts. Overall, 15 lobectomies, 6 pneumonectomies and 4 wedge resections were performed. Details of the type and the number of anastomosed vessels are presented in Table 2 . In each case a complete lymphadenectomy was performed. Each patient had separate pleural and mediastinal tubes inserted at the end of the procedure. All the patients were given low-molecular weight heparin until their discharge from hospital.

The statistical analysis was carried out using StatXact (Cytel Studio v. 8.0, Cytel Inc., Cambridge, MA, USA) and Statistica v.7.1 (StatSoft Inc., Tulsa, OK, USA).

The exact Wilcoxon–Gehan test was used for censored survival data to compare patients in two groups formed on the basis of metastatic disease, extent of pulmonary resection and cardiac status. An influence of accompanying diseases was tested by the Wilcoxon–Gehan (Breslow) test for survival data (Monte Carlo estimate). The p value was considered statistically significant at the level less than 0.05.

The survival curve of all patients was drawn using the Kaplan–Meier method.

	3. Results

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 
There were no deaths and no new MI occurred in the perioperative period. One patient required a re-thoracotomy due to postoperative bleeding. The mean quantity of postoperative drainage was 540 cc (300–1200 cc). The chest tubes and mediastinal drains were kept in situ until the third postoperative day, or longer if the daily amount of drainage collected was greater than 150 cc. The most frequent complications were as follows: cardiac rhythm disturbances, mainly atrial fibrillation (six patients), atelectasis (three patients), residual pneumothorax and a prolonged air-leak (three patients). One patient had serious infectious complications secondary to a broncho-pleural fistula and pleural empyema. Appropriate drainage, followed by thoracostomy and a subsequent myoplastic procedure, resulted in complete recovery. Two patients required mechanical ventilation due to respiratory insufficiency caused by pulmonary edema and pneumonia. The average period of hospital stay was 8 days (6–28 days) with a mean ICU stay of 3 days. There was no significant impact of underlying medical conditions (obesity, gender or a smoking history) on the early operative results.

The duration of follow-up varied from 8 months to 5 years. Eight patients died during this time. The most frequent cause of death was distant metastases and local cancer relapse (six patients) with the majority of the deaths occurring in the first two postoperative years. One patient died due to a cerebral stroke and in one case the cause of death was unknown. According to the Kaplan–Meier survival analysis, the operated patients had a 50% chance of 3-year survival (Fig. 1 ). A recurrence of the cancer was found in 55% of the operated patients. The earliest recurrence was in the 8th postoperative month. There was no significant impact of the following factors on long-term survival: age, gender, history of heart infarction, impaired left ventricular function, the cancer clinical stage or pathology type, pulmonary function, the type of resection, the number of anastomosed vessels and the surgical morbidity. No comorbidities had a significant impact on the long-term survival rate. The only statistically significant factor having an impact on survival was cancer recurrence (p < 0.01). No patient in the entire follow-up period had a MI. Three patients had cardiac events including a recurrence of the angina symptoms and one of them underwent coronary stent implantation.

View larger version (28K): [in this window] [in a new window]   Fig. 1. Kaplan–Meier survival curves of operated patients.

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 
In many European countries, leadership in the decision-making process regarding the treatment of patients with both lung cancer and unstable angina belongs to the thoracic surgeon. Cardiac surgeons encounter this dilemma only in incidental cases where a lung nodule is diagnosed on a routine preoperative chest X-ray. The coincidence of these two entities requires a prompt therapeutic regimen of the ischemic heart disease to minimize the perioperative risk of the lung resection. This regimen requires a prior coronary angiogram and subsequent stent placement or surgical bypass grafting. Many clinicians, including thoracic surgeons, tend to choose the cardiologic invasive procedures as their first treatment choice. However, this approach has important disadvantages. First of all, not all the patients with unstable angina, or those in whom previous cardiologic intervention has failed, are good candidates for this kind of treatment. Especially, management of patients with restenosis or with progressive narrowing of coronary vessels previously not dilated or stented poses a significant problem. This group of patients should, in our opinion, undergo the combined, one-stage cardiothoracic surgical procedure. Moreover, there is the important issue of the side-effects of antiplatelet therapy if cardiologic intervention precedes pulmonary resection. Recent publications regarding the early complications of surgical treatment involving coronary stenting report a significant risk of major intraoperative cardiac ischemia, including the risk of myocardial infarction, six weeks after the stenting [8,9]. Some authors even suggest that this risk may persist for as long as 3 months [10]. However, such delays are unacceptable once lung cancer has been diagnosed. Another approach to this problem could be a simple preoperative coronaroplasty with subsequent stenting after the lung resection [9]. However, a better option appears to be a two-stage approach with surgical myocardial revascularization as the first stage and lung resection as the second, 1 month later. However, in our opinion the two-stage approach also has its disadvantages. Two general anesthesias are required plus two separate chest incisions resulting in increased perioperative stress and pain. Also, the overall hospital stay is longer, thereby increasing the cost. All the drawbacks of the two-stage approach mentioned above are absent with the one-stage procedure.

In the one-stage approach, CABG is usually performed on the beating heart (off-pump CABG) and therefore the risks of cancer spread, intraoperative hemorrhage, the sudden inflammatory response (SIRS) or pulmonary edema, all of which are related to the side-effects of cardiopulmonary bypass, are markedly lower [5,11,12]. In contrast to these reports Schoenmakers et al., in his comparative study did not show any evidence that off-pump surgery is a better option than traditional CPB surgery in the treatment of patients with combined cardiac and pulmonary disease [13]. In reviewing the literature from 1995 to 2005 we found very few publications presenting the results of simultaneous resection of the lung cancer and off-pump CABG in large series of patients. These publications mainly consisted of case reports and case series, usually without recording the long-term results of treatment [14–19]. Although our paper has some limitations (retrospective study and a relatively small number of patients) it partially fills the gap of paucity of the long-term results. Since 2000, we have routinely performed extended cardiac evaluations of high-risk patients with lung cancer. The criteria for inclusion in this group were patients who either had unstable angina symptoms requiring continuous nitrates or beta-blockade or had a MI between 3 and 12 months prior to the lung cancer diagnosis. Initially, we performed the combined procedure in patients soon after MI (2–3 months) and with the stenosis limited to one or two vessels. The cardiologic interventional procedures that had been carried out on these patients had either been ineffective or were not feasible. In addition, the higher clinical stage of the cancer prompted us to operate as soon as possible. As the study progressed, we tended to perform the combined procedure as our first-line treatment option. One patient also received a hybrid procedure with an additional stenting of the RCA.

Simultaneous off-pump and lung resection procedures require different surgical skills. The sternotomy approach, which is infrequently used by general thoracic surgeons, is especially difficult when performing a left lower lobectomy and the accompanying mediastinal lymph node dissection. Therefore, like Toker et al. [20], we favored a left lateral thoracotomy for the single bypass combined with resection of the left lower lobe and, in some cases, combined it with a left pneumonectomy. A significant difficulty of this approach is the creation of a distal anastomosis on the diaphragmatic surface of the heart. On the other hand, the sternotomy makes dissection of the right mainstem bronchus difficult. Moreover, the intraoperative view of the paraesophageal and subcarinal lymph nodes is obscured. In the case of the latter, a transection of the posterior wall of the pericardial sac may be necessary.

An important aspect of this procedure is the sequence of the operative steps. It is crucial to perform the coronary anastomosis before the lung resection. But in selected cases, it may be necessary to perform a crucial one- or two-vessel revascularization to improve the cardiac muscle blood supply followed by the pulmonary resection and, finally, to carry out the remaining coronary anastomosis.

The early results were encouraging. None of the 25 patients studied died and all could be followed up for long-term assessment. There were also no perioperative MI. The surgical morbidity was 35% with the most common causes being: transient cardiac dysrhythmias (mainly atrial fibrillation), atelectasis or incomplete re-expansion of the lung. The cause of six deaths, the majority of which occurred in the second and third postoperative years, was relapse of the cancer. Only one patient had a cerebral incident and in one patient no cause of death could be established. Also, no comorbidities had a significant impact on the long-term survival rate. Two patients required the restart of nitrate therapy and one coronary angioplasty and stent implantation. The only statistically significant cause of long-term failure was the recurrence of the cancer.

	5. Conclusions

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 
Simultaneous off-pump myocardial revascularization and lung resection is a safe and effective treatment when unstable CHD and lung cancer coexist. In selected patients, this combined procedure may be an alternative to the two-stage approach, surgical or non-surgical (cardiologic) interventions preceding the pulmonary resection.

The only statistically significant factor having an impact on long-term survival is the recurrence of the cancer.

	Acknowledgments

 
We would like to thank Professor Geoffrey Shaw for his contribution to the English version of this paper and for his help in the preparation of the manuscript.

	Footnotes

 
Presented at the 15th European Conference on General Thoracic Surgery, Leuven, Belgium, June 3–6, 2007.

This study was supported by KBN grant no. 2PO5C07128.

	References

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion 5. Conclusions References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Wojciech Dyszkiewicz Marek Jemielity Cezary Piwkowski Mariusz Kasprzyk Bartlomiej Perek Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dyszkiewicz, W. Articles by Kaczmarek, E. Search for Related Content PubMed Articles by Dyszkiewicz, W. Articles by Kaczmarek, E. Related Collections Lung - cancer Coronary disease