j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 2 ( 2 0 1 4 ) 6 2 8 e6 3 4
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Factors affecting major morbidity after video-assisted thoracic surgery for lung cancer Zhiqiang Wang, MD,a,1 Jiru Zhang, MS,b,1 Zhou Cheng, MS,c Xianhua Li, MD, PhD,a Zhenjun Wang, MS,a Chuanxin Liu, MS,a and Zongtao Xie, MSa,* a
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, Wuxi, People’s Republic of China b Department of Anesthesiology, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, Wuxi, People’s Republic of China c Department of Emergency Surgery, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, Wuxi, People’s Republic of China
article info
abstract
Article history:
Background: Video-assisted thoracic surgery (VATS) has been widely applied in the treatment
Received 17 December 2013
of lung cancer. However, few studies have focused on the clinical factors predicting the
Received in revised form
major postoperative complications.
5 May 2014
Methods: Clinical data from 525 patients who underwent resection of primary lung cancer
Accepted 23 July 2014
with VATS from January 2007eAugust 2011 were retrospectively analyzed. Risk factors
Available online 28 July 2014
related to major postoperative complications were assessed by univariate and multivariate analyses with logistic regression.
Keywords:
Results: Major complications occurred in 36 (6.86%) patients, of which seven died (1.33%)
Lung cancer
within
Thoracoscopy
hemothorax, myocardial infarction, heart failure, bronchial fistula, cerebral infarction, and
Surgery
pulmonary embolism. Univariate and multivariate logistic regression analyses demon-
30
d,
postoperatively.
Major
complications
included
respiratory
failure,
Complications
strated that age >70 y (odds ratio [OR], 2.105; 95% confidence interval [CI] 1.205e3.865),
Risk factors
forced expiratory volume during the first second expressed as a percentage of predicted 70% (OR, 2.106; 95% CI 1.147e3.982) combined with coronary heart disease (OR, 2.257; 95% CI 1.209e4.123) were independent prognostic factors for major complications. Conclusions: Age >70 and forced expiratory volume during the first second expressed as a percentage of predicted 70% combined with coronary heart disease are independent prognostic factors for postoperative major complications. Patients in these groups should undergo careful preoperative evaluation and perioperative management. ª 2014 Elsevier Inc. All rights reserved.
* Corresponding author. Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, No. 200, Huihe Road, Wuxi 214062, People’s Republic of China. Tel.: þ86051088682123; fax: þ86051085808820. E-mail address: [email protected] (Z. Xie). 1 These authors equally contributed to this work. 0022-4804/$ e see front matter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2014.07.051
629
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 2 ( 2 0 1 4 ) 6 2 8 e6 3 4
1.
Introduction
According to the statistical data released by the World Health Organization, the incidence and mortality rates for lung cancer are the highest of all malignant tumors [1e3], and continue to steadily increase. For patients with resectable lung cancer, surgery remains the most effective therapy [4,5]. In recent years, video-assisted thoracic surgery (VATS) has been widely applied in the treatment of lung cancer and has been shown to be associated with fewer postoperative complications, without its clinical efficacy being compromised [8e11]. However, postoperative complications still affect the outcome of VATS [6,7], and thus far, few studies have focused on its complications and risk factors in lung cancer. Therefore, to predict and prevent postoperative complications are worthy of further investigation. We retrospectively reviewed the clinical data of 525 patients who underwent thoracoscopic surgery for lung cancer. Risk factors for postoperative complications were assessed by logistic regression analysis. We aimed to discover ways to lower the incidence of postoperative complications and to improve surgical outcomes.
2.
Materials and methods
2.1.
Study subjects
The study protocol was approved by the Ethics Committee of the Affiliated Hospital of Jiangnan University. All subjects provided written informed consent for the retrospective review of their medical records. The data of patients with lung cancer who presented to our institution between January 2007 and August 2011 were reviewed. A total of 1253 patients were selected; 569 (45.4%) patients who underwent VATS met the following selection criteria: (1) diagnosed with clinical stage I lung cancer; (2) operation performed by experienced surgeons who had completed 100 VATS cases for lung cancer; (3) no preoperative radiation or chemotherapy; and (4) no history of previous thoracic surgery or pleurodesis. Of the 569 cases, 44 (7.7%) were excluded due to conversion, resulting in 525 patients who were finally enrolled. Meanwhile, 684 (54.6%) patients who underwent thoracotomy met the following selection criteria: (1) diagnosed with clinical stage I, II, or IIIA lung cancer; (2) operation performed by experienced surgeons who had completed 100 thoracotomy cases for lung cancer; and (3) no preoperative radiation or chemotherapy. All patients also underwent the following routine preoperative testing: physical examination, blood tests, liver and kidney function, electrocardiography, pulmonary function testing, chest X-ray, chest computed tomography (CT), cranial magnetic resonance imaging, bone scintigraphy, ultrasound of the upper abdomen and adrenal glands, and fiberoptic bronchoscopy. According to the TNM staging system of the Union for International Cancer Control in 2009, preoperative staging identified 321 stage I cases and 204 stage II cases in the VATS group. Postoperative pathologic or cytologic diagnoses of lung cancer were obtained in 107 patients. Of the 525 VATS patients, 148 were combined with other diseases (28.2%) at the
time of admission and 43 (8.2%) had 2 concurrent diseases (Table 1).
2.2.
Perioperative management
Patients underwent general anesthesia via double-lumen endotracheal intubation and single-lung ventilation. A 1.5 cm incision was made at the seventh or eighth rib at the midaxillary line. A Stryker 1088i Thoracoscope (30 ; Kalamazoo, MI) was inserted for thoracoscopic inspection. A 3e5 cm manipulation incision was made at the fourth or fifth rib at the anterior axillary line. A 2 cm auxiliary incision was made at the seventh or eighth rib at the posterior axillary line. A coagulation hook, ultrasonic scalpel, dissecting forceps, and
Table 1 e Patient characteristics correlated with early death and major complications. Variable
Number of patients (n, %)
Total 525 (100.0) Gender Female 236 (45.0) Male 289 (55.0) Age 20 pack-year 160 (30.5) 20 pack-year 58 (11.0) Never 307 (58.5) FEV1% > 70 433 (82.5) 70 92 (17.5) CHD Yes 40 (7.6) No 485 (92.4) Diabetes Yes 44 (8.4) No 481 (91.6) Hypertension Yes 51 (9.7) No 474 (90.3) Chronic obstructive lung disease Yes 34 (6.5) No 491 (93.5) Stroke history Yes 23 (4.4) No 502 (95.6) Type of surgery Pneumonectomy 45 (8.6) Lobectomy 394 (75.0) Segmentectomy 80 (15.2) þ wedge resection Explorative 6 (1.1) thoracoscopic Operation time >3 h 126 (24.0) 3 h 399 (76.0)
Death 30 d (n, %)
Major complications (n, %)
7 (1.3)
36 (6.9)
3 (1.3) 4 (1.4)
17 (7.2) 19 (6.6)
4 (1.0) 3 (2.3)
21 (5.3) 15 (11.6)
3 (1.9%) 1 (1.7%) 3 (1.0%)
17 (10.6%) 4 (6.9%) 15 (4.9%)
3 (0.7) 4 (4.3)
23 (5.3) 11 (12.0)
3 (7.5) 4 (0.8)
6 (15.0) 30 (6.2)
1 (2.3) 6 (1.2)
5 (11.4) 31 (6.4)
2 (3.9) 5 (1.1)
6 (11.8) 30 (6.3)
1 (2.9) 6 (1.2)
5 (14.7) 31 (6.3)
1 (4.3) 6 (1.2)
4 (17.4) 32 (6.4)
2 (4.4) 4 (1.0) 1 (1.3)
7 (16.6) 24 (6.1) 5 (6.3)
0 (0.0)
0 (0.0)
2 (1.6) 5 (1.3)
13 (10.3) 23 (5.8)
FEV1% ¼ forced expiratory volume in the first second expressed as a percent predicted.
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linear cut stapler were used under thoracoscopic guidance without expanding the intercostal spaces. Intrathoracic adhesions were lysed. The pulmonary veins, arteries, and bronchi were ligated with a linear cutting stapler. Pulmonary resections were performed in a lobar, segmental, or wedge manner depending on the size and location of the lesion. Resected specimens were placed in a bag and removed through the manipulation incision. Mediastinal and hilar lymphadenopathy was performed. We ensured that no residual neoplasm remained at the bronchial resection margins. Postoperatively, an analgesia pump was used for pain control in all patients, as well as broad-spectrum antibiotic prophylaxis. Adjuvant chemotherapy and/or radiotherapy were performed in some patients.
2.3.
Follow-up and survival
Follow-up was carried out by telephone, written correspondence, or clinical assessment. Data including death within 30 d, postoperative complications, and overall survival (OS) were collected. The time when complications were first recorded was defined as occurrence of complications. Followup was carried out every 1e3 mo in the first year and every 3e6 mo thereafter for at least 5 y. The study was completed on September 30, 2013. Twenty-seven patients were lost to follow-up, with an overall follow-up rate of 95.9% and a median follow-up period of 51 (range 6e80) months. The end point of follow-up was death. The following clinical information was collected: blood tests, thoracic and cerebral CT, bone scintigraphy, B-ultrasound of the abdomen and neck, fiberoptic bronchoscopy, and positron emission tomographycomputed tomography when necessary.
2.4.
Statistical analysis
A total of 525 patients were divided into two groups according to the development of postoperative complications. Intergroup differences (clinical and pathologic characteristics) were compared using the chi-square test or Fisher exact test. For factors with a P value 70 y, FEV1% 70%, and concurrent CHD were independent prognostic factors. Other studies showed pneumonectomy and FEV1% 70% to be risk factors for complications after conventional thoracotomy for lung cancer. Pneumonectomy is an independent prognostic factor for death within 30 d after conventional thoracotomy [12]. To a certain extent, the factors which would have caused complications after thoracoscopy were different than those after conventional thoracotomy; for example, the minimally invasive nature of thoracoscopy and patient selection. However, for both approaches, FEV1% 70% was found to be an independent risk factor for postoperative complications after surgery for lung cancer. Thoracoscopic pneumonectomy can reduce mortality within 30 d of surgery, as well as the incidence of postoperative complications. Studies have shown that mortality in patients with lung cancer aged >70 y who undergo thoracoscopic resection is 2.3%, whereas the incidence of postoperative complications is 38.4%. The postoperative mortality in patients with lung cancer aged >75 y is 4.3% and the incidence of complications is 52% [13]. The major organ systems in patients aged >70 y undergo considerable change, with a decline in resistance and organ function as well as a reduction in functional reserve. According to this study, age >70 y was a risk factor for postoperative complications in patients who underwent VATS for lung cancer. The incidence of major postoperative complications was 2.2-fold higher for patients aged 70 y had a higher risk of postoperative complications. Surgical procedure-related risks increase with age, so one should be especially prudent when choosing the surgical approach for patients with lung cancer aged >70 y. Some scholars believe that age is not an important factor affecting outcome [14,15] and state that it could correlate with patient selection. Forty of 525 patients also had CHD (7.6%) in the present study. Multivariate logistic regression analysis showed that the presence of CHD was an independent prognostic factor for major complications. The postoperative mortality of patients
Table 4 e Univariate and multivariate analyses of risk factors related to major complications. Risk factors
CHD FEV1% 0.05; and (B) stratified by CHD and non-CHD, P > 0.05; and (C) stratified by FEV1%, P > 0.05; and (D) stratified by age, P > 0.05; and (E) stratified by pneumonectomy and nonpneumonectomy, P [ 0.032.
with lung cancer and CHD increased eight-fold, whereas the incidence of major complications increased two-fold. Effective perioperative management is crucial for reducing the risk of postoperative death and complications. A careful search should be made to recognize CHD prior to surgery, and for myocardial ischemia by electrocardiogram. For patients with unstable angina pectoris or a history of myocardial infarction, coronary artery angiography is recommended. If there
are obvious signs of obstructive coronary artery disease, percutaneous transluminal coronary angioplasty and stent placement could be carried out before thoracoscopy, or coronary artery bypass surgery in combination with thoracoscopy [16,17]. Vasodilators should be given to patients with mild stenosis, along with glucose-insulin-potassium solution. During anesthesia, oxygen saturations should be maintained above 95%. The principles of expeditious, accurate, and gentle
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 2 ( 2 0 1 4 ) 6 2 8 e6 3 4
manipulation are important. Operative time should be minimized to avoid traction and stimulation of the heart, as well as interference with cardiopulmonary functions. Telemetry monitoring should be performed continuously postoperatively to provide early intervention for arrhythmias and to prevent acute myocardial infarction. Intravenous nitroglycerin should be administered to increase coronary blood flow and to improve myocardial blood supply. Analgesia and cathartics should be regularly given. Of the 40 cases in this study cohort, three died and 37 survived the perioperative period. Preoperative pulmonary function testing has become routine in patients with lung cancer. Numerous indicators have been used to evaluate pulmonary function before conventional thoracotomy in patients with lung cancer. The indicator with the highest predictive value is FEV1% [18,19]. FEV1% is superior to FEV1 for predicting the risks of conventional lobectomy. It is a sensitive indicator for predicting postoperative complications [18,19]. Recently, emphysema has been shown to have an influence on the location of lung cancer and is an independent predictor of long-term survival [20]. In this study, there were 92 of 525 cases with an FEV1% 70% (17.5%). Multivariate logistic regression analysis showed that FEV1% 70% was an independent prognostic factor for major complications. The mortality was six-fold than that of the FEV1% 70% group and the incidence of complications was two-fold than that of the FEV1% >70% group. Possible mechanisms of conventional thoracotomy in decreased pulmonary function in the early stages after surgery may include [21]: restrictive respiratory function due to pain; fewer active coughs due to pain; increased exudation of pulmonary alveoli leading to obstructive respiratory dysfunction; and impaired respiratory function due to transection of intercostal muscles. For the 92 patients with an FEV1% 70%, inhaled nebulizers were administered preoperatively, in combination with improving respiratory function and infection control. Six patients demonstrated postoperative respiratory insufficiency, requiring ventilatory support. Intravenous infusions were reduced and diuretics were administered. Finally, four patients recovered and two patients died. On the second postoperative day, one case demonstrated respiratory insufficiency but recovered after a period of mechanical ventilation; thus, the duration of mechanical ventilation should be prolonged for patients with FEV1% 70%, to facilitate recovery. However, studies also indicated that VATS is less invasive and thus has less of an impact on pulmonary function, and that thoracoscopic lobectomy can be safely performed in patients with impaired lung function [22]. These different conclusions may be attributed to differences in patient condition and perioperative management. Thus, we believe that VATS imputes less damage to lung function compared with thoracotomy, although lung function is still an important indicator for the safety of VATS in any particular case. The literature suggests that pneumonectomy by conventional thoracotomy is an important factor influencing postoperative complications and death [12,14]. In this study, of the 45 patients who underwent pneumonectomy, two (4.4%) died, a higher mortality rate than the 1.0% observed in lobectomy. The incidence of major postoperative complications was 16.6%, also higher than the 6.1% observed with lobectomy. However, the statistical analysis showed that
633
pneumonectomy cannot be used as an independent predictive factor for major postoperative complications. This may be associated with the minimal invasiveness of thoracoscopy, patient selection, and mastery of surgical indications. Additionally, we found that major postoperative complications after lobectomy (6.1%) were similar to those after segmentectomy and wedge resection (6.3%). Moreover, survival is superior after lobectomy compared with segmentectomy for early stage non-small cell lung cancer for tumors >2 cm in size, but 70 y, and an FEV1% 70% did not correlate with OS. The OS of patients undergoing pneumonectomy was obviously lower than those who did not undergo pneumonectomy (OR ¼ 2.43, P ¼ 0.038). Thus, caution should be taken when choosing pneumonectomy for patients. The limitations of our study included two aspects. First, this was a single-center retrospective analysis with a small sample size, not a randomized double blinded study. Thus, confounding and selection bias could not be avoided. Additionally, not all patients received postoperative adjuvant chemotherapy and/or radiotherapy, which would inevitably affect prognosis.
5.
Conclusions
In conclusion, age >70 y, FEV1% 70%, and concomitant CHD were identified as independent risk factors for major complications in patients undergoing VATS for lung cancer. Preoperative evaluation of these risk factors would help to predict the likelihood of perioperative death and major complications. With this information, patients in these groups should undergo careful preoperative evaluation and perioperative management. This work will help to formulate clinical guidance to reduce perioperative death and major complications.
Acknowledgment Authors’ contributions: Z.X. and Z.W. contributed to the conception and design. Z.W. and J.Z. did the writing of the article. J.Z., Z.C., and C.L. did the data collection. X.L. and Z.W. did the analysis and interpretation. Z.X. did the critical revision of the article.
Disclosure The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in the article.
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references [14] [1] Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893. [2] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69. [3] Alberg AJ, Ford JG, Samet JM. American College of Chest Physicians. Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132:29S. [4] Higton AM, Monach J, Congleton J. Investigation and management of lung cancer in older adults. Lung Cancer 2010;69:209. [5] Hurria A, Kris MG. Management of lung cancer in older adults. CA Cancer J Clin 2003;53:325. [6] Strand TE, Rostad H, Damhuis RA, Norstein J. Risk factors for 30-day mortality after resection of lung cancer and prediction of their magnitude. Thorax 2007;62:991. [7] Ayed AK, Bazerbashi S, Chandrasekaran C, Sukumar M, Jamaleddin H. Pulmonary complications following major lung resection for benign and malignant lung diseases. Med Princ Pract 2006;15:114. [8] Scott WJ, Matteotti RS, Egleston BL, Oseni S, Flaherty JF. A comparison of perioperative outcomes of video-assisted thoracic surgical (VATS) lobectomy with open thoracotomy and lobectomy: results of an analysis using propensity score based weighting. Ann Surg Innov Res 2010;4:1. [9] Sugi K, Kobayashi S, Sudou M, Sakano H, Matsuda E, Okabe K. Long-term prognosis of video-assisted limited surgery for early lung cancer. Eur J Cardiothorac Surg 2010; 37:456. [10] D’Amico TA, Niland J, Mamet R, Zornosa C, Dexter EU, Onaitis MW. Efficacy of mediastinal lymph node dissection during lobectomy for lung cancer by thoracoscopy and thoracotomy. Ann Thorac Surg 2011;92:226. discussion 231. [11] Papiashvilli M, Stav D, Cyjon A, Haitov Z, Gofman V, Bar I. Lobectomy for non-small cell lung cancer: differences in morbidity and mortality between thoracotomy and thoracoscopy. Innovations (Phila) 2012;7:15. [12] Myrdal G, Gustafsson G, Lambe M, Horte LG, Stahle E. Outcome after lung cancer surgery. Factors predicting early mortality and major morbidity. Eur J Cardiothorac Surg 2001; 20:694. [13] Berry MF, Hanna J, Tong BC, Burfeind WR Jr, Harpole DH, D’Amicox TA. Risk factors for morbidity after lobectomy for
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lung cancer in elderly patients. Ann Thorac Surg 2009;88: 1093. Dell’Amore A, Monteverde M, Martucci N, Sanna S, Caroli G, Stella F. Early and long-term results of pulmonary resection for non-small-cell lung cancer in patients over 75 years of age: a multi-institutional study. Interact Cardiovasc Thorac Surg 2013;16:250. Chambers A, Routledge T, Pilling J, Scarci M. In elderly patients with lung cancer is resection justified in terms of morbidity, mortality and residual quality of life? Interact Cardiovasc Thorac Surg 2010;10:1015. Watanabe F, Hataji O, Ito K, D’Alessandro-Gabazza CN, Naito M, Morooka H. Three-dimensional computed tomography angiography for the preoperative evaluation of coronary artery disease in lung cancer patients. World J Surg Oncol 2013;11:164. Dyszkiewicz W, Jemielity M, Piwkowski C, Kasprzyk M, Perek B, Gasiorowski L. 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. Eur J Cardiothorac Surg 2008;34:531. Kearney DJ, Lee TH, Reilly JJ, DeCamp MM, Sugarbaker DJ. Assessment of operative risk in patients undergoing lung resection. Importance of predicted pulmonary function. Chest 1994;105:753. Scanlon PD. Assessment of operative risk in patients undergoing lung resection. Importance of predicted pulmonary function. Chest 1994;105:654. Bishawi M, Moore W, Bilfinger T. Severity of emphysema predicts location of lung cancer and 5-y survival of patients with stage I non-small cell lung cancer. J Surg Res 2013;184:1. Zhang Z, Liu D, Guo Y, Shi B, Tian Y, Song Z. The common causes of conversion of VATS during operation for 248 nonsmall cell lung cancers. Zhongguo Fei Ai Za Zhi 2011;14:523. Berry MF, Villamizar-Ortiz NR, Tong BC, Burfeind WR Jr, Harpole DH, D’Amico TA. Pulmonary function tests do not predict pulmonary complications after thoracoscopic lobectomy. Ann Thorac Surg 2010;89:1044. discussion 1051. Bao F, Ye P, Yang Y, Wang L, Zhang C, Lv X. Segmentectomy or lobectomy for early stage lung cancer: a meta-analysis. Eur J Cardiothorac Surg 2014;46:1. Yendamuri S, Sharma R, Demmy M, Groman A, Hennon M, Dexter E. Temporal trends in outcomes following sublobar and lobar resections for small ( ¼ 2 cm) non-small cell lung cancersea Surveillance Epidemiology End Results database analysis. J Surg Res 2013;183:27.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Factors affecting major morbidity after video-assisted thoracic surgery for lung cancer Zhiqiang Wang, MD,a,1 Jiru Zhang, MS,b,1 Zhou Cheng, MS,c Xianhua Li, MD, PhD,a Zhenjun Wang, MS,a Chuanxin Liu, MS,a and Zongtao Xie, MSa,* a
Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, Wuxi, People’s Republic of China b Department of Anesthesiology, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, Wuxi, People’s Republic of China c Department of Emergency Surgery, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, Wuxi, People’s Republic of China
article info
abstract
Article history:
Background: Video-assisted thoracic surgery (VATS) has been widely applied in the treatment
Received 17 December 2013
of lung cancer. However, few studies have focused on the clinical factors predicting the
Received in revised form
major postoperative complications.
5 May 2014
Methods: Clinical data from 525 patients who underwent resection of primary lung cancer
Accepted 23 July 2014
with VATS from January 2007eAugust 2011 were retrospectively analyzed. Risk factors
Available online 28 July 2014
related to major postoperative complications were assessed by univariate and multivariate analyses with logistic regression.
Keywords:
Results: Major complications occurred in 36 (6.86%) patients, of which seven died (1.33%)
Lung cancer
within
Thoracoscopy
hemothorax, myocardial infarction, heart failure, bronchial fistula, cerebral infarction, and
Surgery
pulmonary embolism. Univariate and multivariate logistic regression analyses demon-
30
d,
postoperatively.
Major
complications
included
respiratory
failure,
Complications
strated that age >70 y (odds ratio [OR], 2.105; 95% confidence interval [CI] 1.205e3.865),
Risk factors
forced expiratory volume during the first second expressed as a percentage of predicted 70% (OR, 2.106; 95% CI 1.147e3.982) combined with coronary heart disease (OR, 2.257; 95% CI 1.209e4.123) were independent prognostic factors for major complications. Conclusions: Age >70 and forced expiratory volume during the first second expressed as a percentage of predicted 70% combined with coronary heart disease are independent prognostic factors for postoperative major complications. Patients in these groups should undergo careful preoperative evaluation and perioperative management. ª 2014 Elsevier Inc. All rights reserved.
* Corresponding author. Department of Thoracic and Cardiovascular Surgery, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, No. 200, Huihe Road, Wuxi 214062, People’s Republic of China. Tel.: þ86051088682123; fax: þ86051085808820. E-mail address: [email protected] (Z. Xie). 1 These authors equally contributed to this work. 0022-4804/$ e see front matter ª 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2014.07.051
629
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 2 ( 2 0 1 4 ) 6 2 8 e6 3 4
1.
Introduction
According to the statistical data released by the World Health Organization, the incidence and mortality rates for lung cancer are the highest of all malignant tumors [1e3], and continue to steadily increase. For patients with resectable lung cancer, surgery remains the most effective therapy [4,5]. In recent years, video-assisted thoracic surgery (VATS) has been widely applied in the treatment of lung cancer and has been shown to be associated with fewer postoperative complications, without its clinical efficacy being compromised [8e11]. However, postoperative complications still affect the outcome of VATS [6,7], and thus far, few studies have focused on its complications and risk factors in lung cancer. Therefore, to predict and prevent postoperative complications are worthy of further investigation. We retrospectively reviewed the clinical data of 525 patients who underwent thoracoscopic surgery for lung cancer. Risk factors for postoperative complications were assessed by logistic regression analysis. We aimed to discover ways to lower the incidence of postoperative complications and to improve surgical outcomes.
2.
Materials and methods
2.1.
Study subjects
The study protocol was approved by the Ethics Committee of the Affiliated Hospital of Jiangnan University. All subjects provided written informed consent for the retrospective review of their medical records. The data of patients with lung cancer who presented to our institution between January 2007 and August 2011 were reviewed. A total of 1253 patients were selected; 569 (45.4%) patients who underwent VATS met the following selection criteria: (1) diagnosed with clinical stage I lung cancer; (2) operation performed by experienced surgeons who had completed 100 VATS cases for lung cancer; (3) no preoperative radiation or chemotherapy; and (4) no history of previous thoracic surgery or pleurodesis. Of the 569 cases, 44 (7.7%) were excluded due to conversion, resulting in 525 patients who were finally enrolled. Meanwhile, 684 (54.6%) patients who underwent thoracotomy met the following selection criteria: (1) diagnosed with clinical stage I, II, or IIIA lung cancer; (2) operation performed by experienced surgeons who had completed 100 thoracotomy cases for lung cancer; and (3) no preoperative radiation or chemotherapy. All patients also underwent the following routine preoperative testing: physical examination, blood tests, liver and kidney function, electrocardiography, pulmonary function testing, chest X-ray, chest computed tomography (CT), cranial magnetic resonance imaging, bone scintigraphy, ultrasound of the upper abdomen and adrenal glands, and fiberoptic bronchoscopy. According to the TNM staging system of the Union for International Cancer Control in 2009, preoperative staging identified 321 stage I cases and 204 stage II cases in the VATS group. Postoperative pathologic or cytologic diagnoses of lung cancer were obtained in 107 patients. Of the 525 VATS patients, 148 were combined with other diseases (28.2%) at the
time of admission and 43 (8.2%) had 2 concurrent diseases (Table 1).
2.2.
Perioperative management
Patients underwent general anesthesia via double-lumen endotracheal intubation and single-lung ventilation. A 1.5 cm incision was made at the seventh or eighth rib at the midaxillary line. A Stryker 1088i Thoracoscope (30 ; Kalamazoo, MI) was inserted for thoracoscopic inspection. A 3e5 cm manipulation incision was made at the fourth or fifth rib at the anterior axillary line. A 2 cm auxiliary incision was made at the seventh or eighth rib at the posterior axillary line. A coagulation hook, ultrasonic scalpel, dissecting forceps, and
Table 1 e Patient characteristics correlated with early death and major complications. Variable
Number of patients (n, %)
Total 525 (100.0) Gender Female 236 (45.0) Male 289 (55.0) Age 20 pack-year 160 (30.5) 20 pack-year 58 (11.0) Never 307 (58.5) FEV1% > 70 433 (82.5) 70 92 (17.5) CHD Yes 40 (7.6) No 485 (92.4) Diabetes Yes 44 (8.4) No 481 (91.6) Hypertension Yes 51 (9.7) No 474 (90.3) Chronic obstructive lung disease Yes 34 (6.5) No 491 (93.5) Stroke history Yes 23 (4.4) No 502 (95.6) Type of surgery Pneumonectomy 45 (8.6) Lobectomy 394 (75.0) Segmentectomy 80 (15.2) þ wedge resection Explorative 6 (1.1) thoracoscopic Operation time >3 h 126 (24.0) 3 h 399 (76.0)
Death 30 d (n, %)
Major complications (n, %)
7 (1.3)
36 (6.9)
3 (1.3) 4 (1.4)
17 (7.2) 19 (6.6)
4 (1.0) 3 (2.3)
21 (5.3) 15 (11.6)
3 (1.9%) 1 (1.7%) 3 (1.0%)
17 (10.6%) 4 (6.9%) 15 (4.9%)
3 (0.7) 4 (4.3)
23 (5.3) 11 (12.0)
3 (7.5) 4 (0.8)
6 (15.0) 30 (6.2)
1 (2.3) 6 (1.2)
5 (11.4) 31 (6.4)
2 (3.9) 5 (1.1)
6 (11.8) 30 (6.3)
1 (2.9) 6 (1.2)
5 (14.7) 31 (6.3)
1 (4.3) 6 (1.2)
4 (17.4) 32 (6.4)
2 (4.4) 4 (1.0) 1 (1.3)
7 (16.6) 24 (6.1) 5 (6.3)
0 (0.0)
0 (0.0)
2 (1.6) 5 (1.3)
13 (10.3) 23 (5.8)
FEV1% ¼ forced expiratory volume in the first second expressed as a percent predicted.
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linear cut stapler were used under thoracoscopic guidance without expanding the intercostal spaces. Intrathoracic adhesions were lysed. The pulmonary veins, arteries, and bronchi were ligated with a linear cutting stapler. Pulmonary resections were performed in a lobar, segmental, or wedge manner depending on the size and location of the lesion. Resected specimens were placed in a bag and removed through the manipulation incision. Mediastinal and hilar lymphadenopathy was performed. We ensured that no residual neoplasm remained at the bronchial resection margins. Postoperatively, an analgesia pump was used for pain control in all patients, as well as broad-spectrum antibiotic prophylaxis. Adjuvant chemotherapy and/or radiotherapy were performed in some patients.
2.3.
Follow-up and survival
Follow-up was carried out by telephone, written correspondence, or clinical assessment. Data including death within 30 d, postoperative complications, and overall survival (OS) were collected. The time when complications were first recorded was defined as occurrence of complications. Followup was carried out every 1e3 mo in the first year and every 3e6 mo thereafter for at least 5 y. The study was completed on September 30, 2013. Twenty-seven patients were lost to follow-up, with an overall follow-up rate of 95.9% and a median follow-up period of 51 (range 6e80) months. The end point of follow-up was death. The following clinical information was collected: blood tests, thoracic and cerebral CT, bone scintigraphy, B-ultrasound of the abdomen and neck, fiberoptic bronchoscopy, and positron emission tomographycomputed tomography when necessary.
2.4.
Statistical analysis
A total of 525 patients were divided into two groups according to the development of postoperative complications. Intergroup differences (clinical and pathologic characteristics) were compared using the chi-square test or Fisher exact test. For factors with a P value 70 y, FEV1% 70%, and concurrent CHD were independent prognostic factors. Other studies showed pneumonectomy and FEV1% 70% to be risk factors for complications after conventional thoracotomy for lung cancer. Pneumonectomy is an independent prognostic factor for death within 30 d after conventional thoracotomy [12]. To a certain extent, the factors which would have caused complications after thoracoscopy were different than those after conventional thoracotomy; for example, the minimally invasive nature of thoracoscopy and patient selection. However, for both approaches, FEV1% 70% was found to be an independent risk factor for postoperative complications after surgery for lung cancer. Thoracoscopic pneumonectomy can reduce mortality within 30 d of surgery, as well as the incidence of postoperative complications. Studies have shown that mortality in patients with lung cancer aged >70 y who undergo thoracoscopic resection is 2.3%, whereas the incidence of postoperative complications is 38.4%. The postoperative mortality in patients with lung cancer aged >75 y is 4.3% and the incidence of complications is 52% [13]. The major organ systems in patients aged >70 y undergo considerable change, with a decline in resistance and organ function as well as a reduction in functional reserve. According to this study, age >70 y was a risk factor for postoperative complications in patients who underwent VATS for lung cancer. The incidence of major postoperative complications was 2.2-fold higher for patients aged 70 y had a higher risk of postoperative complications. Surgical procedure-related risks increase with age, so one should be especially prudent when choosing the surgical approach for patients with lung cancer aged >70 y. Some scholars believe that age is not an important factor affecting outcome [14,15] and state that it could correlate with patient selection. Forty of 525 patients also had CHD (7.6%) in the present study. Multivariate logistic regression analysis showed that the presence of CHD was an independent prognostic factor for major complications. The postoperative mortality of patients
Table 4 e Univariate and multivariate analyses of risk factors related to major complications. Risk factors
CHD FEV1% 0.05; and (B) stratified by CHD and non-CHD, P > 0.05; and (C) stratified by FEV1%, P > 0.05; and (D) stratified by age, P > 0.05; and (E) stratified by pneumonectomy and nonpneumonectomy, P [ 0.032.
with lung cancer and CHD increased eight-fold, whereas the incidence of major complications increased two-fold. Effective perioperative management is crucial for reducing the risk of postoperative death and complications. A careful search should be made to recognize CHD prior to surgery, and for myocardial ischemia by electrocardiogram. For patients with unstable angina pectoris or a history of myocardial infarction, coronary artery angiography is recommended. If there
are obvious signs of obstructive coronary artery disease, percutaneous transluminal coronary angioplasty and stent placement could be carried out before thoracoscopy, or coronary artery bypass surgery in combination with thoracoscopy [16,17]. Vasodilators should be given to patients with mild stenosis, along with glucose-insulin-potassium solution. During anesthesia, oxygen saturations should be maintained above 95%. The principles of expeditious, accurate, and gentle
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manipulation are important. Operative time should be minimized to avoid traction and stimulation of the heart, as well as interference with cardiopulmonary functions. Telemetry monitoring should be performed continuously postoperatively to provide early intervention for arrhythmias and to prevent acute myocardial infarction. Intravenous nitroglycerin should be administered to increase coronary blood flow and to improve myocardial blood supply. Analgesia and cathartics should be regularly given. Of the 40 cases in this study cohort, three died and 37 survived the perioperative period. Preoperative pulmonary function testing has become routine in patients with lung cancer. Numerous indicators have been used to evaluate pulmonary function before conventional thoracotomy in patients with lung cancer. The indicator with the highest predictive value is FEV1% [18,19]. FEV1% is superior to FEV1 for predicting the risks of conventional lobectomy. It is a sensitive indicator for predicting postoperative complications [18,19]. Recently, emphysema has been shown to have an influence on the location of lung cancer and is an independent predictor of long-term survival [20]. In this study, there were 92 of 525 cases with an FEV1% 70% (17.5%). Multivariate logistic regression analysis showed that FEV1% 70% was an independent prognostic factor for major complications. The mortality was six-fold than that of the FEV1% 70% group and the incidence of complications was two-fold than that of the FEV1% >70% group. Possible mechanisms of conventional thoracotomy in decreased pulmonary function in the early stages after surgery may include [21]: restrictive respiratory function due to pain; fewer active coughs due to pain; increased exudation of pulmonary alveoli leading to obstructive respiratory dysfunction; and impaired respiratory function due to transection of intercostal muscles. For the 92 patients with an FEV1% 70%, inhaled nebulizers were administered preoperatively, in combination with improving respiratory function and infection control. Six patients demonstrated postoperative respiratory insufficiency, requiring ventilatory support. Intravenous infusions were reduced and diuretics were administered. Finally, four patients recovered and two patients died. On the second postoperative day, one case demonstrated respiratory insufficiency but recovered after a period of mechanical ventilation; thus, the duration of mechanical ventilation should be prolonged for patients with FEV1% 70%, to facilitate recovery. However, studies also indicated that VATS is less invasive and thus has less of an impact on pulmonary function, and that thoracoscopic lobectomy can be safely performed in patients with impaired lung function [22]. These different conclusions may be attributed to differences in patient condition and perioperative management. Thus, we believe that VATS imputes less damage to lung function compared with thoracotomy, although lung function is still an important indicator for the safety of VATS in any particular case. The literature suggests that pneumonectomy by conventional thoracotomy is an important factor influencing postoperative complications and death [12,14]. In this study, of the 45 patients who underwent pneumonectomy, two (4.4%) died, a higher mortality rate than the 1.0% observed in lobectomy. The incidence of major postoperative complications was 16.6%, also higher than the 6.1% observed with lobectomy. However, the statistical analysis showed that
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pneumonectomy cannot be used as an independent predictive factor for major postoperative complications. This may be associated with the minimal invasiveness of thoracoscopy, patient selection, and mastery of surgical indications. Additionally, we found that major postoperative complications after lobectomy (6.1%) were similar to those after segmentectomy and wedge resection (6.3%). Moreover, survival is superior after lobectomy compared with segmentectomy for early stage non-small cell lung cancer for tumors >2 cm in size, but 70 y, and an FEV1% 70% did not correlate with OS. The OS of patients undergoing pneumonectomy was obviously lower than those who did not undergo pneumonectomy (OR ¼ 2.43, P ¼ 0.038). Thus, caution should be taken when choosing pneumonectomy for patients. The limitations of our study included two aspects. First, this was a single-center retrospective analysis with a small sample size, not a randomized double blinded study. Thus, confounding and selection bias could not be avoided. Additionally, not all patients received postoperative adjuvant chemotherapy and/or radiotherapy, which would inevitably affect prognosis.
5.
Conclusions
In conclusion, age >70 y, FEV1% 70%, and concomitant CHD were identified as independent risk factors for major complications in patients undergoing VATS for lung cancer. Preoperative evaluation of these risk factors would help to predict the likelihood of perioperative death and major complications. With this information, patients in these groups should undergo careful preoperative evaluation and perioperative management. This work will help to formulate clinical guidance to reduce perioperative death and major complications.
Acknowledgment Authors’ contributions: Z.X. and Z.W. contributed to the conception and design. Z.W. and J.Z. did the writing of the article. J.Z., Z.C., and C.L. did the data collection. X.L. and Z.W. did the analysis and interpretation. Z.X. did the critical revision of the article.
Disclosure The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in the article.
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