Asian Cardiovasc Thorac Ann 2005;13:311-315
© 2005 Asia Publishing EXchange Ltd
Long-Term Pulmonary Function after Lobectomy for Primary Lung Cancer
Yasunobu Funakoshi, MD,
Shin-ichi Takeda, MD,
Noriyoshi Sawabata, MD,
Yoshitomo Okumura, MD,
Hajime Maeda, MD
Division of General Thoracic Surgery, Toneyama National Hospital, Osaka, Japan
For reprint information contact: Yasunobu Funakoshi, MD Tel: 81 6 6853 2001 Fax: 81 6 6850 1750 Email: funakosy{at}toneyama.go.jp, Division of General Thoracic Surgery, Toneyama National Hospital, 5-5-1 Toneyama, Toyonaka, Osaka 560-8552, Japan.
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ABSTRACT
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The aim of this study was to investigate the factors affecting long-term postoperative pulmonary function with a view to increasing the application of combined resection, bronchoplasty, and induction therapy. Results in 80 patients who underwent lobectomy for primary lung cancer were analyzed. Predicted postoperative pulmonary function was calculated using the formula: postoperative predicted function = preoperative function x [1 – (b – n) /(42 – n)], where n and b are the numbers of obstructed segments and total segments, respectively, in the resected lobe. Spirometry was performed serially on the preoperative day, and at 3, 6, 12, 18, and 24 months postoperatively. The difference between the predicted postoperative pulmonary function and the function measured at 12 months postoperatively was calculated, and clinical and therapeutic variables were analyzed. Univariate analysis revealed that the difference in vital capacity was significantly related to surgical approach, bronchoplasty, and induction therapy, while the difference in forced expiratory volume in one second (FEV1) correlated with surgical approach and induction therapy. Multiple regression analysis showed induction therapy to be the sole factor related to the differences in both vital capacity and FEV1. Lung resection after induction therapy may cause an additional loss of pulmonary function in the late phase.
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INTRODUCTION
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Lung cancer is the leading cause of cancer-related mortality in the United States as well as Japan.1 Complete resection offers the best chance of cure and long-term survival in patients with non-small cell lung cancer. Over the past decade, the emergence of induction therapy followed by surgery has enabled patients with advanced lung cancer to obtain a favorable 5-year survival rate.2–3 Thus, its availability has increased the prevalence of operable advanced lung cancer. The prediction of pulmonary functional reserve after lung resection plays a crucial role, along with disease staging, in determining operative procedures and predicting postoperative quality of life.4–8 Although many previous studies have focused on short-term postoperative pulmonary function, there have been few studies on the factors that affect long-term (> 1 year) postoperative pulmonary function.9 We retrospectively investigated the changes over time in pulmonary function after lobectomy, and the relationship of clinical and therapeutic variables with long-term pulmonary function after lobectomy as a means of elucidating the selection process of candidates for modern surgical techniques.
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PATIENTS AND METHODS
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Between January 1997 and December 1998, 127 patients underwent lung resection for primary lung cancer at our institution. Postoperative spirometry could not be obtained in 13 patients (6 patients died within 1 year because of relapse, 2 were referred back to regional hospitals, and 3 refused postoperative spirometry). Another 31 patients who were treated by other surgical procedures (9 pneumonectomies, 15 bilobectomies, 4 segmentectomies, and 3 wedge resections) and 3 who received postoperative therapy were excluded. The remaining 80 patients (45 men and 35 women; mean age, 62.4 ± 10.6 years) who underwent a single lobectomy were enrolled in this retrospective study. Thirty-eight were in clinical stage IA, 22 in stage IB, 5 in stage IIB, 12 in stage IIIA, and 3 in stage IIIB. Twenty-three had a right upper lobectomy, 7 had a right middle lobectomy, 17 had a right lower lobectomy, 25 had a left upper lobectomy, and 8 had a left lower lobectomy. An anterior axillary thoracotomy through the 4th intercostal space was adopted in principle, however other approaches were employed, especially when combined resections were required. All surgical procedures were performed by the same surgical team. Eleven patients received preoperative induction therapy: 1 in clinical stage IA, 9 in stage IIIA, 1 in stage IIIB. The preoperative chemotherapeutic regimen consisted of 2 combinations: cisplatin and vindesine in 4 patients; and cisplatin, vindesine, and mitomycin in 6. All of these patients, except for 1 in the cisplatin and vindesine therapy group, received 2 cycles of chemotherapy, and all but 1 received radiation therapy with an average of 38 Gy. At 12 months postoperatively, 10 patients had local recurrences or distant metastases.
Spirometry was performed on the preoperative day, and then at 3, 6, 12, 18, and 24 months after surgery using an Autospirometer System 9 (Minato Medical Science, Osaka, Japan). Predicted postoperative pulmonary function was calculated using the formula: predicted postoperative function = preoperative function x [1 – (b – n) /(42 – n)], where b = number of segments to be resected and n = number of obstructed segments in that lobe.4,5,10 The formula was based on the assumption that b was 6, 4, and 12 in the right upper, middle, and lower lobes, respectively, and 10 in each of the left upper and lower lobes.4 The predicted values were compared with the actual data and the resulting differences were expressed as: 
% vital capacity (VC) = measured postoperative %VC - predicted %VC; and % forced expiratory volume (FEV1) in one sec = measured postoperative %FEV1 - predicted %FEV1. Statistical analyses were performed using %VC and %FEV1 calculations for the 12th postoperative month.
Clinical and therapeutic variables related to long-term postoperative pulmonary function were: sex, age, smoking history (Brinkman index: the number of cigarettes smoked per day multiplied by years of smoking), performance status, surgical approach, bronchoplasty, nodal dissection, and induction therapy.11 Univariate analyses were performed using the Mann-Whitney U test to compare differences between 2 groups. Variables with a p value of < 0.05 were used for multiple regression analysis. A p value of < 0.05 was regarded as statistically significant.
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RESULTS
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Preoperative pulmonary function tests showed restrictive impairment in 2 patients and obstructive impairment in 8. The mean (± standard deviation) measured preoperative VC and FEV1 were 3.18 ± 0.74 L and 2.22 ± 0.54 L, respectively. As expected, VC and FEV1 were impaired in the early postoperative phase; however, they both gradually improved and reached a stable level by the 12th postoperative month (Figure 1
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Figure 1. Changes in postoperative pulmonary function. Vital capacity (VC) (Left) and forced expiratory volume (FEV1) in 1 sec (Right) were impaired in the early postoperative phase but they improved gradually and stabilized by the 12th postoperative month (M).
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The clinical characteristics of the patients are shown in Table 1. Univariate analysis of the patient characteristics revealed that sex, age, smoking history, and performance status had no effect on long-term postoperative pulmonary function in terms of %VC and %FEV1. Therapeutic variables are shown in Table 2. In univariate analysis of the therapeutic factors, %VC was significantly related to surgical approach, bronchoplasty, and induction therapy, while %FEV1 was significantly related to surgical approach and induction therapy. Multiple regression analysis revealed that induction therapy was the only factor that had any effect on postoperative %VC and %FEV1 (Table 3). Among the patients who received induction therapy followed by surgery, VC and FEV1 did not improve in the late postoperative phase, in contrast to those who underwent surgery alone (Figure 2). The %VC per resected segment of the surgery-only group and that of the induction therapy group was 0.34 and -1.46, respectively. The %FEV1 per resected segment of the surgery-only group and of the induction therapy group was 0.45 and –1.00, respectively.
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Figure 2. Postoperative pulmonary function with and without induction therapy. In patients who received induction therapy, vital capacity (VC) (Left) and forced expiratory volume (FEV1) in 1 sec (Right) did not improve in the late postoperative phase, in contrast to patients who underwent surgery alone. Broken line: surgery alone (n = 69), solid line: induction therapy (n = 11).
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DISCUSSION
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When we evaluate lung cancer patients preoperatively, operability addresses the question of how much pulmonary tissue can be safely removed without rendering the patient a pulmonary cripple. Thus, the preoperative estimation of residual pulmonary function is as crucial as TNM staging and resectability in such patients. In the 1980s, regional pulmonary function was investigated using radiospirometry to establish an accurate means of estimating postoperative pulmonary function.6,12 Nakahara and colleagues4,7 stated that their formula was a reliable method for predicting postoperative pulmonary function after all surgical procedures, based on an intensive analysis of pulmonary function. The same formula was used in this study.
In the early postoperative period, surgical trauma is the main factor influencing postoperative pulmonary function. Thus, decreases in VC and FEV1 are derived from restrictive damage to the chest wall and reduced muscular activity by the diaphragm.13–14 In other words, neural depression due to pain causes a decrease in respiratory muscle power, which results in a decrease in VC and FEV1. Accordingly, our results regarding the changes of VC and FEV1 indicate a gradual improvement in postoperative pulmonary function which reaches a stable condition 12 months after surgery. Therefore, we selected values obtained 12 months postoperatively to represent stable long-term postoperative pulmonary function. Combined resection of the chest wall may further decrease pulmonary function. Nakata and colleagues13 reported that in the early postoperative period, VC and FEV1 were better after video-assisted thoracic surgery than after a thoracotomy; whereas 1 year after the procedure, they could not find any difference in pulmonary function between the 2 groups, indicating that video-assisted thoracic surgery does not have an impact on long-term pulmonary function. Khargi and colleagues9 found that postoperative pulmonary function completely recovered 4 months after performing bronchoplasty, similar to the results with a standard lobectomy. Bronchoplasty, which shows a slightly higher morbidity and mortality than standard lobectomy, is not considered to adversely affect long-term postoperative pulmonary function.9,15
Both radiation therapy and chemotherapy have the potential to compromise pulmonary function reserve, and a variety of chemotherapeutic drugs have been recognized as causative agents of lung injury.16 Due to acute pneumonitis and late pulmonary fibrosis, pulmonary function after radiation therapy decreases, and many chemotherapeutic drugs are known to significantly increase the risk of developing radiation-induced pulmonary injury, which may be accentuated when chemotherapy and radiation therapy are administered concurrently.17 In an analysis of the effect of radiation on pulmonary function, the volume of the irradiated lung did not predict a late decrease in pulmonary function, while decreases in diffusing capacity were resolved 1 to 2 years after radiation.18 However, combined multimodality treatment with surgery followed by radiation therapy might result in additional loss of pulmonary function; patients who received adjuvant radiation therapy had a larger decline in pulmonary function than those who underwent lobectomy alone.19
Although many studies of induction therapy have focused mainly on survival, operative morbidity, and operative mortality, the various clinical and therapeutic variables have not been evaluated with reference to long-term postoperative pulmonary function in patients given induction therapy. Our results showed that VC and FEV1 of the induction therapy group did not improve in the late postoperative phase, in contrast to the surgery-only group. Induction therapy was the only independent factor that had a negative effect on long-term postoperative pulmonary function following a single lobectomy. The %VC per resected segment and %FEV1 per resected segment of the induction therapy group were also significantly lower than the surgery-only group. In agreement with the results of Granone and colleagues,20 postoperative recovery of pulmonary function was impaired in patients who received induction therapy. In our previous analysis of complications, 4 of 35 patients who underwent a single lobectomy after induction therapy suffered interstitial pneumonia or radiation pneumonitis postoperatively, and 1 patient died due to an operation-related complication.4,12 Furthermore, 2 of these patients required home oxygen therapy despite the prediction of adequate pulmonary function. These results suggest a detrimental effect of induction therapy on long-term postoperative pulmonary function. Moreover, our multiple regression analysis showed a significant decline in pulmonary function in patients given induction therapy, which was the sole independent risk factor. However, further investigation with a larger number of patients is needed to clarify the discrepancies in pulmonary function between early and late results. It was concluded that lung resection combined with induction therapy may result in additional pulmonary function loss in the late postoperative phase, which should be recognized when weighing various therapeutic options for modern surgical candidates with lung cancer.
Presented at the Annual Meeting of the American Thoracic Society (ATS International Conference), May 16–21, 2003, Seattle, WA, USA.
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ABSTRACT
INTRODUCTION
