Study searches and characteristics
The detailed process of literature retrieval procedures is shown in Fig. 1. A total of 29 eligible studies were finally included in the present meta-analysis (3, 5–20, 24–35). These studies were carried out in the following geographical regions: five in USA (8, 19, 20, 32, 35), four in China (3, 11, 25, 26), four in Netherlands (7, 13, 30, 33), three in Italy (14, 18, 29), two in Czech Republic (12, 24), two in Japan (10, 16), two in Turkey (9, 15), one in Australia (34), one in Belgium (6), one in Canada (31), one in Germany (5), one in Greece (27), one in Poland (28), and one in UK (17). All of them were retrospective observational studies, which were published between 1990 and 2019. Of these studies, the sample sizes ranged from 2 to 79 patients. Therefore, 29 studies containing 536 patients who received combined heart surgery and lung tumor resection were subjected to final analysis. In each study, the proportion estimates with their corresponding 95% CIs of the operative mortality and postoperative complications were calculated from available information from original article. Quality scores evaluated by the Newcastle–Ottawa Scale (NOS) ranged from 5 to 7. The main characteristics of all included studies have been summarized in Table 1.
Table 1: Characteristics of studies included in the meta-analysis.
Study
|
Year
|
Country
|
Study design
|
Study period
|
No. of patients
|
Lung pathology (Adenocarcinoma/
squamous cell carcinoma/
other malignant tumors/
benign tumors)
|
Heart surgery (CABG/
other types of heart surgery)
|
Operative mortality proportions (95% CI)
|
Postoperative complication proportions (95% CI)
|
Li
|
2019
|
China
|
Case-control
|
2009-2016
|
20
|
13/6/1/0
|
20/0
|
0.00 [0.00; 0.17]
|
0.00 [0.00; 0.17]
|
Yeginsu
|
2018
|
Turkey
|
Retrospective
|
2014-2018
|
10
|
3/6/1/0
|
10/0
|
0.10 [0.00; 0.45]
|
0.40 [0.12; 0.74]
|
Kaku
|
2017
|
Japan
|
Retrospective
|
2008-2013
|
18
|
13/2/0/3
|
6/12
|
0.00 [0.00; 0.19]
|
0.00 [0.00; 0.19]
|
Ma
|
2016
|
China
|
Retrospective
|
2003-2014
|
34
|
18/16/0/0
|
34/0
|
0.00 [0.00; 0.10]
|
0.32 [0.17; 0.51]
|
Santavy
|
2015
|
Czech Republic
|
Retrospective
|
2010-2014
|
10
|
3/0/3/4
|
6/4
|
0.00 [0.00; 0.31]
|
0.10 [0.00; 0.45]
|
Kovacicova
|
2014
|
Czech Republic
|
Case-control
|
2002-2011
|
12
|
1/7/4/0
|
9/3
|
0.00 [0.00; 0.26]
|
0.75 [0.43; 0.95]
|
Zhang
|
2012
|
Germany
|
Retrospective
|
1999-2007
|
30
|
6/5/1/18
|
17/13
|
0.07 [0.01; 0.22]
|
0.10 [0.02; 0.27]
|
Li
|
2012
|
China
|
Retrospective
|
2008-2010
|
3
|
1/2/0/0
|
3/0
|
0.00 [0.00; 0.71]
|
0.00 [0.00; 0.71]
|
Zhang
|
2009
|
China
|
Retrospective
|
2003-2008
|
7
|
2/5/0/0
|
7/0
|
0.00 [0.00; 0.41]
|
0.14 [0.00; 0.58]
|
Cathenis
|
2009
|
Belgium
|
Retrospective
|
2000-2008
|
27
|
10/14/2/1
|
22/5
|
0.00 [0.00; 0.13]
|
1.00 [0.87; 1.00]
|
Prokakis
|
2008
|
Greece
|
Retrospective
|
2004-2006
|
5
|
1/2/0/2
|
1/4
|
0.00 [0.00; 0.52]
|
0.40 [0.05; 0.85]
|
Dyszkiewicz
|
2008
|
Poland
|
Retrospective
|
2001-2006
|
25
|
6/14/5/0
|
25/0
|
0.00 [0.00; 0.14]
|
0.64 [0.43; 0.82]
|
Schoenmakers
|
2007
|
Netherlands
|
Case-control
|
1994-2005
|
43
|
17/17/9/0
|
37/6
|
0.07 [0.01; 0.19]
|
0.67 [0.51; 0.81]
|
Caimmi
|
2006
|
Italy
|
Retrospective
|
2005-2006
|
2
|
1/1/0/0
|
2/0
|
0.00 [0.00; 0.84]
|
0.00 [0.00; 0.84]
|
Patane
|
2002
|
Italy
|
Retrospective
|
1991-1999
|
11
|
2/7/0/2
|
6/5
|
0.00 [0.00; 0.28]
|
0.00 [0.00; 0.28]
|
Koksal
|
2002
|
Turkey
|
Retrospective
|
2001-2002
|
2
|
0/2/0/0
|
2/0
|
0.00 [0.00; 0.84]
|
0.00 [0.00; 0.84]
|
Morishita
|
2001
|
Japan
|
Retrospective
|
1986-2000
|
6
|
3/2/1/0
|
4/2
|
0.00 [0.00; 0.46]
|
0.83 [0.36; 1.00]
|
Mariani
|
2001
|
Netherlands
|
Retrospective
|
1999-2000
|
3
|
2/1/0/0
|
3/0
|
0.00 [0.00; 0.71]
|
0.00 [0.00; 0.71]
|
Danton
|
1998
|
UK
|
Retrospective
|
1990-1997
|
13
|
6/3/2/2
|
11/2
|
0.00 [0.00; 0.25]
|
0.62 [0.32; 0.86]
|
Voets
|
1997
|
Netherlands
|
Case-control
|
1988-1995
|
24
|
8/14/2/0
|
24/0
|
0.21 [0.07; 0.42]
|
0.79 [0.58; 0.93]
|
Rao
|
1996
|
Canada
|
Retrospective
|
1982-1995
|
30
|
10/5/6/9
|
24/6
|
0.07 [0.01; 0.22]
|
0.23 [0.10; 0.42]
|
Francesca
|
1995
|
USA
|
Retrospective
|
1973-1990
|
21
|
11/7/3/0
|
18/3
|
0.05 [0.00; 0.24]
|
0.29 [0.11; 0.52]
|
Brutel
|
1995
|
Netherlands
|
Retrospective
|
1979-1993
|
79
|
22/48/9/0
|
69/10
|
0.06 [0.02; 0.14]
|
0.86 [0.76; 0.93]
|
Terzi
|
1994
|
Italy
|
Retrospective
|
1980-1993
|
10
|
2/3/3/2
|
10/0
|
0.10 [0.00; 0.45]
|
0.40 [0.12; 0.74]
|
Miller
|
1994
|
USA
|
Case-control
|
1965-1992
|
30
|
19/8/3/0
|
23/7
|
0.07 [0.01; 0.22]
|
0.50 [0.31; 0.69]
|
Yokoyama
|
1993
|
USA
|
Retrospective
|
1988-1992
|
11
|
6/4/1/0
|
9/2
|
0.00 [0.00; 0.28]
|
0.64 [0.31; 0.89]
|
Rosalion
|
1993
|
Australia
|
Retrospective
|
1987-1990
|
10
|
4/5/1/0
|
10/0
|
0.00 [0.00; 0.31]
|
0.80 [0.44; 0.97]
|
Ulicny
|
1992
|
USA
|
Retrospective
|
1980-1990
|
19
|
4/0/6/9
|
14/5
|
0.05 [0.00; 0.26]
|
1.00 [0.82; 1.00]
|
Canver
|
1990
|
USA
|
Retrospective
|
1982-1988
|
21
|
4/4/0/13
|
18/3
|
0.05 [0.00; 0.24]
|
0.10 [0.01; 0.30]
|
Pooled Proportion Of Operative Mortality
The pooled proportion of operative mortality was 0.01 (95% CI: 0.00, 0.03) using both fixed-effect and random-effect models. No significant heterogeneity between studies was shown (I2 = 0.00%, P = 0.79) (Fig. 2).
Pooled Proportion Of Postoperative Complications
The pooled proportion of postoperative complications was 0.40 (95% CI: 0.24, 0.57) using the random-effect model. Significant heterogeneity between studies was noted (I2 = 91.60%, P < 0.01) (Fig. 3).Furthermore, we divided the postoperative complications into three categories: reopening for bleeding; respiratory complications and cardiac complications. The pooled proportion of reopening for bleeding was 0.01 (95% CI: 0.00, 0.02) using both fixed-effect and random-effect models. No significant heterogeneity between studies was shown (I2 = 2.10%, P = 0.43) (Fig. 4). The pooled proportion of respiratory complications was 0.11 (95% CI: 0.04, 0.19) using the random-effect model. Significant heterogeneity between studies was noted (I2 = 76.00%, P < 0.01). The pooled proportion of cardiac complications was 0.15 (95% CI: 0.08, 0.23) using the random-effect model. Significant heterogeneity between studies was noted (I2 = 72.00%, P < 0.01).
Subgroup Analysis
For further assessing the incidence rates of operative mortality and postoperative complications of patients who received combined heart surgery and lung tumor resection, we classified all cases into several subgroups according to lung pathology and heart surgery procedures.
In the subgroups classified by lung pathology, 16 studies (3, 7–9, 11, 13–16, 19, 26, 28, 30, 32–34) contained 327 patients who received combined heart surgery and lung cancer resection, while the other 13 studies (5, 6, 10, 12, 17, 18, 20, 24, 25, 27, 29, 31, 35) enrolled both malignant and benign diseases. Because malignant and benign diseases were analyzed together in the 13 studies (5, 6, 10, 12, 17, 18, 20, 24, 25, 27, 29, 31, 35), further assessment of benign diseases was not done. So, we quantitatively pooled the data of 327 lung cancer cases from the 16 studies (3, 7–9, 11, 13–16, 19, 26, 28, 30, 32–34). The pooled proportion of operative mortality of patients who received combined heart surgery and lung cancer resection was 0.01 (95% CI: 0.00, 0.04) using both fixed-effect and random-effect models. No significant heterogeneity between studies was shown (I2 = 2.20%, P = 0.43). The pooled proportion of postoperative complications of patients who received combined heart surgery and lung cancer resection was 0.45 (95% CI: 0.27, 0.64) using the random-effect model. Significant heterogeneity between studies was noted (I2 = 87.80%, P < 0.01).
To further estimate the quality control of lung cancer surgery, we concerned about whether patients with lung cancer had underwent anatomical resection and systematic lymph node dissection or sampling. The pooled proportion of lung cancer patients underwent anatomical resection was 0.99 (95% CI: 0.95, 1.00) using the random-effect model. Significant heterogeneity between studies was noted (I2 = 54.70%, P < 0.01) (Fig. 5). Among the 16 studies (3, 7–9, 11, 13–16, 19, 26, 28, 30, 32–34), 1 study did not provide enough information about lymph node dissection or sampling (7). Therefore, 15 studies (3, 8, 9, 11, 13–16, 19, 26, 28, 30, 32–34) containing 303 patients who received combined heart surgery and lung cancer resection were used to analyze the proportion of systematic lymph node dissection or sampling. The pooled proportion of lung cancer patients underwent systematic lymph node dissection or sampling was 1.00 (95% CI: 1.00, 1.00) using both fixed-effect and random-effect models. No significant heterogeneity between studies was shown (I2 = 4.20%, P = 0.41) (Fig. 6).
In the subgroups classified by heart surgery procedures, 10 studies (3, 9, 11, 14, 15, 18, 26, 28, 30, 34) contained 123 patients who received combined coronary artery bypass grafting (CABG) surgery and lung tumor resection, while the other 19 studies (5–8, 10, 12, 13, 16, 17, 19, 20, 24, 25, 27, 29, 31–33, 35) enrolled both CABG surgery and other types of heart surgery procedures. Because CABG surgery and other types of heart surgery procedures were analyzed together in the 19 studies (5–8, 10, 12, 13, 16, 17, 19, 20, 24, 25, 27, 29, 31–33, 35), further assessment of heart surgery procedures other than CABG was not done. So, we quantitatively pooled the data of 123 CABG cases from the 10 studies (3, 9, 11, 14, 15, 18, 26, 28, 30, 34). The pooled proportion of operative mortality of patients who received combined CABG surgery and lung tumor resection was 0.00 (95% CI: 0.00, 0.01) using both fixed-effect and random-effect models. No significant heterogeneity between studies was shown (I2 = 0.00%, P = 0.76). The pooled proportion of postoperative complications of patients who received combined CABG surgery and lung tumor resection was 0.26 (95% CI: 0.07, 0.50) using the random-effect model. Significant heterogeneity between studies was noted (I2 = 79.80%, P < 0.01).
To further evaluate the impact of cardiopulmonary bypass on postoperative complications, we compared off-pump with on-pump on postoperative complications of CABG patients. The pooled proportion of postoperative complications of CABG patients using off-pump method was 0.17 (95% CI: 0.01, 0.43) using the random-effect model. Significant heterogeneity between studies was noted (I2 = 79.40%, P < 0.01). The pooled proportion of postoperative complications of CABG patients using on-pump method was 0.61 (95% CI: 0.38, 0.82) using fixed-effect model. No significant heterogeneity between studies was shown (I2 = 67.40%, P = 0.08) (Fig. 7).
Sensitivity Analysis And Publication Bias
Sensitivity analysis showed that no individual study influenced the overall results (Fig. 8). Funnel plot for publication bias of the pooled proportion of postoperative complications for all studies was shown in Fig. 9. Begg’s test (P = 0.42) and Egger’s test (P = 0.07) demonstrated non-significant publication bias.