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Ann Thorac Surg 2002;74:999-1003
© 2002 The Society of Thoracic Surgeons

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Original article: general thoracic

Predictors of early morbidity after major lung resection in patients with and without airflow limitation

^a Department of Thoracic Surgery, University of Ancona, Ancona, Italy

Accepted for publication June 5, 2002.

* Address reprint requests to Dr Brunelli, Via S. Margherita 23, Ancona 60129, Italy
e-mail: alexit_2000{at}yahoo.com

	Abstract

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Background. The aim of the present study was to identify predictors of morbidity after major lung resection for non-small cell lung carcinoma in patients with forced expiratory volume in 1 second (FEV₁) greater than or equal to 70% of predicted and in those with FEV₁ less than 70% of predicted.

Methods. Five hundred forty-four patients who underwent lobectomy or pneumonectomy from 1993 through 2000 were retrospectively analyzed. The patients were divided into two groups: group A (450 cases), with FEV₁ greater than or equal to 70%, and group B (94 cases), with FEV₁ less than 70%. Differences between complicated and uncomplicated patients were tested within each group.

Results. Morbidity rate was not significantly different between group A and group B (20.4% and 24.5%, respectively; p = 0.4). In group A, multivariate analysis showed that predicted postoperative FEV₁ was the only significant independent predictor of complications. In group B, no significant predictor was identified.

Conclusions. In patients with preoperative FEV₁ less than 70% of predicted, predicted postoperative FEV₁ was not predictive of postoperative morbidity. Thus, predicted postoperative FEV₁ should not be used alone as a selection criteria for operation in these high-risk patients.

	Introduction

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
A large number of candidates for lung resection for non-small cell lung carcinoma have a concomitant chronic obstructive pulmonary disease (COPD) [1]. The presence of COPD has been associated with an increased risk of postoperative cardiopulmonary complications and mortality [2–4]. The aim of the present study was to assess whether predictors of morbidity after lobectomy or pneumonectomy for non-small cell lung carcinoma in patients without airflow limitation may apply to those with airflow limitation as well.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Five hundred eighty-five consecutive patients underwent lung resection for non-small cell lung carcinoma at our institution from 1993 through 2000. Of these, 41 were excluded from the present study because they had incomplete preoperative or postoperative data or because they underwent minor resections (wedge or segmentectomy).

Thus, 544 patients (470 male, 74 female) who underwent lobectomy (414 cases) or pneumonectomy (130 cases) for non-small cell lung carcinoma (265 squamous cell carcinoma, 254 adenocarcinoma, 25 large cell carcinoma) formed the database of the present study. This is a retrospective analysis performed on a prospectively compiled computerized database.

Resectability was assessed by means of computed tomographic scan, bronchoscopy, and, when indicated, cervical mediastinoscopy.

Operability was evaluated as follows: pulmonary function tests, blood gas analysis, electrocardiogram, echocardiography, and a more-invasive cardiologic procedure if needed. Operation was indicated in patients with a predicted postoperative forced expiratory volume in 1 second (ppoFEV₁) greater than 30% of predicted, according to the cutoff values proposed by Markos and associates [5]. All patients with a concomitant cardiac disease were judged hemodynamically stable at the time of operation.

Postoperative complications and mortality were considered as those occurring within 30 days postoperatively, or for a longer period if the patient was still in the hospital.

According to previous studies [5, 6] and for the sake of comparison, the following complications were included: respiratory failure requiring mechanical ventilation for more than 48 hours; pneumonia; atelectasis requiring bronchoscopy; adult respiratory distress syndrome; pulmonary edema; pulmonary embolism; myocardial infarction; hemodynamically unstable arrhythmia requiring medical treatment and prolonged hospital stay; cardiac failure; fever higher than 38°C for more than 3 days; or death. Mortality was not separately analyzed owing to small numbers.

According to the criteria proposed by the European Respiratory Society [7], the patients were divided into two groups: group A (450 cases), with a preoperative FEV₁ of or greater than 70% of predicted, and group B (94 cases), with an FEV₁ less than 70% of predicted. All patients in group B had an FEV₁ to forced vital capacity (FVC) ratio less than 89% (mean, 70.7% ± 11.6%), indicative of a predominant functional obstructive pattern [7].

The following variables were tested within each group for the association with postoperative complications: age, arterial oxygen tension, arterial carbon dioxide level, preoperative hemoglobin concentration, serum albumin level, type of operation (lobectomy versus pneumonectomy), type of resection (extended versus nonextended), pathologic T status (pT1 + pT2 versus pT3 + pT4), pathologic N status (pN-negative versus pN-positive), presence of concomitant cardiac disease, neoadjuvant chemotherapy, preoperative pulmonary function tests (FEV₁, FEV₁/FVC, ppoFEV₁, COPD index, residual volume to total lung capacity), percentage of functional parenchyma removed at operation.

For the purpose of the present study a resection was considered extended when associated with resection of parietal pleura (extrapleural resections), chest wall, mediastinal structures, or diaphragm.

Pathologic T and N descriptors were classified according to the 1997 International System for Staging Lung Cancer [8]. There were 169 patients with pT1, 252 with pT2, 91 with pT3, and 32 with pT4 tumor stage. pT4 tumors included satellite tumor nodules within the ipsilateral primary tumor lobe (22 cases), invasion of mediastinum (5 cases), invasion of superior vena cava (2 cases), and malignant pleural effusion (3 cases). Furthermore, 368 patients had pN0, 107 had pN1, and 69 had pN2 lymph node stage.

A concomitant cardiac disease was defined as follows: previous cardiac operation, previous myocardial infarction, history of coronary artery disease, or current treatment for arrhythmia, cardiac failure, or hypertension.

Pulmonary function tests were performed according to the American Thoracic Society criteria. Results of spirometry were collected after bronchodilator administration.

Values for FEV₁ and ppoFEV₁ were expressed as percentage of predicted for age, sex, and height, according to the European Community for Steel and Coal prediction equations [9]. The ppoFEV₁ was calculated by the following formula:

The number of functioning segments was estimated by means of computed tomographic scan and bronchoscopy findings. In patients with a calculated ppoFEV₁ less than 50% of predicted and in all pneumonectomy candidates, a quantitative perfusion lung scan was used, according to Markos and coworkers [5]. The simple calculation of ppoFEV₁ was previously shown to be as accurate as perfusion lung scanning [5].

Chronic obstructive pulmonary disease index was calculated by adding FEV₁ in decimal form to FEV₁/FVC as proposed by Korst and associates [10].

The percentage of functional parenchyma removed during operation was estimated by means of computed tomographic scan, bronchoscopy, and, when performed, quantitative perfusion lung scan.

The comparison between complicated and uncomplicated patients within each group was performed by means of the unpaired Student’s t test for numerical variables and by means of the ² test for categorical variables. The significant variables at univariate analysis were then entered as independent variables in a multivariate logistic regression analysis (dependent variable, presence of postoperative complications). All the statistical tests were two-tailed and a significance level of 0.05 was accepted. The analysis was performed by using the StatView 5.0 software (SAS Institute, Cary, NC).

	Results

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
The morbidity rate in the entire population was 21.1% (115 cases), whereas the mortality rate was 2.9% (16 cases). There were 151 complications in 115 patients. Complications in order of frequency were arrhythmia (44 cases), fever greater than 38°C for more than 3 days (29 cases), pneumonia (22 cases), respiratory failure (22 cases), atelectasis (17 cases), myocardial infarction (6 cases), cardiac failure (4 cases), adult respiratory distress syndrome (3 cases), pulmonary edema (3 cases), and pulmonary embolism (1 case).

The results of the comparison between the two groups of patients are shown in Tables 1 and 2. In particular, group B patients (FEV₁ < 70%) were older, had a lower FEV₁, FEV₁/FVC, ppoFEV₁, COPD index, and arterial oxygen tension with respect to group A patients (FEV₁ 70%). Moreover, group B patients had an increased ratio of residual volume to total lung capacity and arterial carbon dioxide tension values and an increased rate of concomitant cardiac disease compared with group A patients. Obstructed patients had also a significantly lower percentage of functioning lung tissue removed during operation.

Table 3 shows the comparison between complicated and uncomplicated patients in group A (FEV₁ 70%). Patients with complications had a reduced FEV₁, ppoFEV₁, and COPD index. Furthermore, the loss of functional lung tissue was greater in the complicated patients with respect to the uncomplicated ones. Complications were also more frequent in pneumonectomy than in lobectomy.

In group B (FEV₁ < 70%), none of the variables used for the comparison in group A was found to significantly differ between patients with and those without complications. Thus, no multivariate analysis was performed. In particular, ppoFEV₁ was 44.5% in the complicated patients and 45.3% in the uncomplicated ones.

	Comment

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Approximately 80% of patients with lung cancer have a concomitant COPD, and 20% to 30% have severe pulmonary dysfunction [1]. A reduced FEV₁ has been associated with an increased risk of postoperative complications after lung resection for carcinoma [3, 11–13]. However, other authors have reported different results [5, 14–16].

The main objective of the present study was to assess whether predictors of postoperative risk in patients with normal or almost normal FEV₁ may apply to patients with moderate to severe airflow limitation as well. For this reason, we chose an FEV₁ value of 70% of predicted as a cutoff, according to the COPD severity classification proposed by the European Respiratory Society (FEV₁ < 70%: moderate to severe COPD) [7]. In this class of COPD, FEV₁ expressed as percentage of predicted values has been considered the best indicator of the severity of the airflow limitation [9].

In group B of our analysis, the patients had the typical characteristics of obstructive pulmonary disease. They had a reduced FEV₁%, FEV₁/FVC, FVC%, and an increased ratio of residual volume to total lung capacity, showing airflow obstruction and a certain degree of hyperinflation. Moreover, they had a reduced COPD index, which has been described as a reliable indicator of the purity of pulmonary obstructive disease [10].

In our study, patients with airflow limitation did not experience an increased rate of postoperative morbidity and mortality with respect to those with better respiratory functions. This was in accordance with previous reports in which a reduced FEV₁ was not a significant predictor of postoperative risk [5, 14–17].

In group A (FEV₁ 70%), the best predictor of postoperative cardiopulmonary complications was ppoFEV₁. This has been reported by other studies [5, 14, 18]; however, those studies did not analyze patients with different degrees of COPD separately. In group B (FEV₁ < 70%), we were unable to identify a significant predictor of postoperative morbidity, in accordance with another study on similar patients [19]. In particular, ppoFEV₁ was not significantly different between complicated and uncomplicated patients. This finding has already been reported in similarly selected series of high-risk patients [20–24]. To rule out the possibility of a type II error, we calculated the power of the statistical test for this variable, by considering 23 outcomes (complicated cases) of 94 cases, a level of significance of 0.05, and an expected difference between the means of 10 (assumed by the difference between the values of ppoFEV₁ in uncomplicated and complicated patients with FEV₁ 70%). This resulted in a statistical power of 99.9%.

The reason why ppoFEV₁ was not predictive of complications in these patients remains a matter of speculation. Certainly, the unreliability of the estimation of the expected value of FEV₁ in obstructed patients has to be taken into account [5]. Patients with airway obstruction and pulmonary hyperinflation may lose less than expected or even improve their respiratory function after lung resection, as already reported by some authors [10, 12, 17, 25–27]. Furthermore, even though a formal radiologic visual assessment [25] to grade the severity of the emphysema in the resected parenchyma was not performed because of the retrospective nature of the study, the removal of poorly functioning emphysematous lung tissue may have improved lung mechanics and ventilation-perfusion mismatch. In fact, although similar proportions of lobectomy and pneumonectomy were performed in the two groups, patients with FEV₁ less than 70% had a significantly reduced amount of functional lung tissue removed at operation (probably owing to emphysematous destruction) and showed preoperative signs of hyperinflation (increased ratio of residual volume to total lung capacity) and ventilation-perfusion mismatch (reduced arterial oxygen tension, increased arterial carbon dioxide level).

Our work showed that ppoFEV₁ was not a good indicator of postoperative complications in patients with compromised respiratory function. Thus, we think that it should not be used alone to select these patients for major lung resection. It is noteworthy that in group B (FEV₁ < 70%), only 6 of 21 patients (28.6%) with a ppoFEV₁ less than 40% of predicted had complications, and only 1 (4.8%) of them died. Based on the results of this analysis, we recently modified our exclusion criteria for lung resection in lung cancer patients. We currently regard as operable even those patients with a ppoFEV₁ less than 30%, should they show a sufficient aerobic reserve at maximal stair climbing test. In fact, some authors have already demonstrated the reliability of cardiopulmonary exercise tests in predicting the operative risk in compromised patients [20–22, 24].

Even though the present study was a retrospective analysis from a low-volume center and our results need confirmation by larger prospective series, we showed that major lung resection for lung cancer can be safely performed in many patients with airflow limitation. However, factors predicting the postoperative risk remained elusive. Hence, in addition to split lung function, other tests (ie, maximal exercise test) should be prospectively evaluated to limit the improper exclusion of patients with severe airflow obstruction from operation.

	Acknowledgments

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
We thank Maureen Nkwadi, MS, for language assistance.

	References

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 

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