LAPAROSCOPIC VERSUS OPEN SURGERY IN GASTRIC GASTROINTESTINAL STROMAL TUMORS LARGER THAN 5 CM: A SYSTEMATIC REVIEW AND META-ANALYSIS

PITA ARAUJO, Francisco Antonio; LOPES, Vítor Nuno Neves; BARBOSA, Jose Pedro Coimbra de Vargas Lobarinhas; MARTINS, Mariana Rafaela da Fonte; BARBOSA, José

doi:10.1590/0102-672020220002e1711

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ABCD. Arquivos Brasileiros de Cirurgia Digestiva (São Paulo)

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Review Article • ABCD, arq. bras. cir. dig. 35 • 2022 • https://doi.org/10.1590/0102-672020220002e1711 copy

LAPAROSCOPIC VERSUS OPEN SURGERY IN GASTRIC GASTROINTESTINAL STROMAL TUMORS LARGER THAN 5 CM: A SYSTEMATIC REVIEW AND META-ANALYSIS

ABORDAGEM LAPAROSCÓPICA VERSUS CIRURGIA ABERTA EM TUMORES ESTROMAIS GÁSTRICOS SUPERIORES A 5 CM: REVISÃO SISTEMÁTICA E META-ANÁLISE

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

BACKGROUND:

Surgical resection represents the main treatment for resectable nonmetastatic gastric gastrointestinal stromal tumors. Despite the feasibility and safety of laparoscopic resection, its standard use in gastric tumors larger than 5 cm is yet to be established.

AIMS:

This study aimed to compare the current evidence on laparoscopic resection with the classical open surgical approach in terms of perioperative, postoperative, and oncological outcomes.

METHODS:

The PubMed, Scopus, and Web of Science databases were consulted. Articles comparing the approach to gastric gastric gastrointestinal stromal tumors larger than 5 cm by open and laparoscopic surgery were eligible. A post hoc subgroup analysis based on the extent of the surgery was performed to evaluate the operative time, blood loss, and length of hospital stay.

RESULTS:

A total of nine studies met the eligibility criteria. In the study, 246 patients undergoing laparoscopic surgery and 301 patients undergoing open surgery were included. The laparoscopic approach had statistically significant lower intraoperative blood loss (p=0.01) and time to oral intake (p<0.01), time to first flatus (p<0.01), and length of hospital stay (0.01), compared to the open surgery approach. No significant differences were found when operative time (0.25), postoperative complications (0.08), R0 resection (0.76), and recurrence rate (0.09) were evaluated. The comparative subgroup analysis between studies could not explain the substantial heterogeneity obtained in the respective outcomes.

CONCLUSION:

The laparoscopic approach in gastric gastrointestinal stromal tumors larger than 5 cm compared to the open surgical approach is a technically safe and feasible surgical method with similar oncological results.

HEADINGS
Gastrointestinal Stromal Tumors; Laparotomy; Gastrectomy; Minimally Invasive Surgical Procedures; Review

Study (author)	Year	Study design	Country	Years of enrollment	Intervention (n)	Comparison (n)	Outcomes	Sample size, n	Median follow-up (months) (range)
Study (author)	Year	Study design	Country	Years of enrollment	Intervention (n)	Comparison (n)	Outcomes	Sample size, n	LAP	OS
Kim et al.	2012	ROS	Korea	1998–2011	LAP (n=24)	OS (n=14)	A, E, F, G	48	62.6(8.9–164.4)	58.3(18.8–123.2)
Hsiao et al.	2015	ROS	Taiwan	2002–2012	LAP (n=18)	OS (n=21)	A, B, F, G	39	37.2(16.8–133.2)	67.2(12–133.2)
Lin et al.	2014	ROS	China	2007–2012	LAP (n=23)	OS (n=23)	A, B, C, D, E, F, G	46	34(6–78)	34(6–78)
Takahashi et al.	2015	ROS	Japan	1995–2011	LAP (n=12)	OS (n=15)	A, B, E, F, G	27	57(7–120)	69(13–154)
Piessen et al.	2015	ROS	France	2001–2013	LAP (n=90)	OS (n=93)	E, G	183	NR	NR
Xue et al.	2015	ROS	China	2008–2013	LAP (n=19)	OS (n=62)	A, B, D, F,	81	25(7–64)	47(7–84)
Khoo et al.	2017	ROS	Singapore	2002–2015	LAP (n=23)	OS (n=36)	A, B, C, E, F, G	59	20.5(0–163)	78(2–151)
Qiu et al.	2017	ROS	China	2008–2014	LAP (n=24)	OS (n=24)	A, B, C, D, E, F, G	48	50	52
Lian et al.	2017	ROS	China	2008–2015	LAP (n=13)	OS (n=13)	A, B, C, D, E, F, G	26	48(26–78)	42(11–83)

Study (author)	Age (mean±SD)		Sex (M/F)		Tumor size (cm) (mean±SD)		Mitotic rate
	LAP	OS	LAP	OS	LAP	OS	LAP		OS
	LAP	OS	LAP	OS	LAP	OS	<5/ 50 HFPs	>5/ 50 HFPs	<5/ 50 HFPs	>5/ 50 HFPs
Kim et al.	57.4±8.1	65.9±12.2	12/12	4/10	6.1±1.3	7.2±1.7	16	8	5	9
Hsiao et al.	66.6±14	64.5±10.4	8/10	7/14	6.3±1.1	6±0.9	14	4	17	4
Lin et al.	63.4±12.9	62±11.3	11/12	16/7	7.2±1.6	7.3±1.5	16	7	13	10
Takahashi et al.	64 (18-78)*	66 (37–76)*	7/5	10/5	5.5 (5.1–5.7)*	7.5 (5.3–13)*	9	3	10	5
Piessen et al.	NR	NR	NR	NR	NR	NR	NR	NR	NR	RN
Xue et al.	NR	NR	NR	NR	NR	NR	NR	NR	NR	NR
Khoo et al.	61 (31–86)*	66.5 (21–90)*	9/14	19/17	6 (5–11)*	6.25 (5–12.5)*	10	10	13	21
Qiu et al.	65.9±7.9	61.5±10.9	8/16	11/13	7±1.4	7.6±1.75	19	5	16	8
Lian et al.	56.15±12.84	60.73±9.32	5/8	4/9	6 (5–11)	6 (5–11)	6	7	5	8

Study	Laparoscopic surgery n (%)	Open surgery n (%)
(A)
Kim et al., 2012	1/24 (4.2%)	0/14 (0.0%)
Lin et al., 2014	2/23 (8.7%)	3/23 (13.0%)
Takahashi et al., 2015	1/12 (8.3%)	1/15 (6.7%)
Piessen et al., 2015	11/90 (12.2%)	21/93 (22.6%)
Khoo et al., 2017	2/23 (8.7%)	5/36 (13.9%)
Qiu et al., 2017	3/24 (12.5%)	5/24 (20.9%)
Lian et al., 2017	1/13 (7.7%)	0/13 (0.0%)
(B)
Kim et al., 2012	1/24 (4.2%)	4/14 (28.6%)
Lin et al., 2014	3/23 (13.0%)	5/23 (21.7%)
Hsiao et al., 2015	1/18 (5.6%)	0/21 (0.0%)
Takahashi et al., 2015	1/12 (8.3%)	2/15 (13.3%)
Piessen et al., 2015	5/90 (5.6%)	7/93 (7.5%)
Khoo et al., 2017	0/23 (0.0%)	2/36 (5.6%)
Qiu et al., 2017	1/24 (4.2%)	2/24 (8.3%)
Lian et al., 2017	0/13 (0.0%)	1/13 (7.7%)
(C)
Kim et al., 2012	24/24 (100%)	14/14 (100%)
Hsiao et al., 2015	17/18 (94.4%)	19/21 (90.5%)
Qiu et al., 2017	23/24 (95.8%)	23/24 (95.8%)
Lian et al., 2017	13/13 (100%)	13/13 (100%)

(A)
Study	Laparoscopic surgery		Open surgery
Study	Mean(min)	SD(min)	Sample(size)	Mean(min)	SD(min)	Sample(size)
Kim et al., 2012	119.5	62.2	24	154.3	53.5	14
Lin et al., 2014	124.1	50.3	23	196.5	64.8	23
Hsiao et al., 2015	146.6	50.2	18	113.3	42.9	21
Takahashi et al., 2015	123.75*	44.75*	12	119.5*	44.22*	15
Xue et al., 2015	128.9	38.2	19	106	39.2	62
Khoo et al., 2017	210*	81.25*	23	105*	48.75*	36
Qiu et al., 2017	131	44	24	103	30	24
Lian et al., 2017	197.46	59.774	13	129.23	56	13

(B)
Study	Laparoscopic surgery		Open surgery
Study	Mean(mL)	SD(mL)	Sample(size)	Mean(mL)	SD(mL)	Sample(size)
Lin et al., 2014	35.6	28.3	23	127.8	116.8	23
Hsiao et al., 2015	42.2	47.7	18	51.4	58.4	21
Takahashi et al., 2015	202.5*	244.65*	12	255*	262.69*	15
Xue et al., 2015	34.1	26.5	19	60.4	60.4	62
Khoo et al., 2017	78.26*	75*	23	128.47*	125*	36
Qiu et al., 2017	73	36	24	105	51	24
Lian et al., 2017	207.5	175.86	13	105	86.84	13

(C)
Study	Laparoscopic surgery		Open surgery
Study	Mean(days)	SD(days)	Sample(size)	Mean(days)	SD(days)	Sample(size)
Lin et al., 2014	2.3	1.5	23	3.5	2.3	23
Khoo et al., 2017	2.25*	0.75*	23	3*	1.25*	36
Qiu et al., 2017	3.2	0.6	24	3.6	0.8	24
Lian et al., 2017	4.77	1.48	13	4.23	2.45	13

(D)
Study	Laparoscopic surgery		Open surgery
Study	Mean(days)	SD(days)	Sample(size)	Mean(days)	SD(days)	Sample(size)
Lin et al., 2014	1.9	1.2	23	3	1	23
Xue et al., 2015	3.5	1.4	19	3.9	1	62
Qiu et al., 2017	2.2	0.5	24	2.5	0.7	24
Lian et al., 2017	3.69	0.75	13	3.92	1.66	13

(E)
Study	Laparoscopic surgery		Open surgery
Study	Mean(days)	SD(days)	Sample(size)	Mean(days)	SD(days)	Sample(size)
Kim et al., 2012	4.8	1.8	24	9.2	3.2	14
Lin et al., 2014	124.1	50.3	23	196.5	64.8	23
Hsiao et al., 2015	8.4	2.9	18	9.6	2.4	21
Takahashi et al., 2015	14.25*	7.46*	12	18.25*	8.01*	15
Xue et al., 2015	7.2	3.8	19	9	4.8	62
Khoo et al., 2017	221.22*	17.5*	23	21.12*	15*	36
Qiu et al., 2017	6.6	2.2	24	8.1	2.3	24
Lian et al., 2017	7.92	2.66	13	6.69	1.93	13

Study	MINORS item												Total
Study	1)	2)	3)	4)	5)	6)	7)	8)	9)	10)	11)	12)	Total
Kim et al., 2012	2	2	1	2	0	2	2	1	2	2	1	1	18
Lin et al., 2014	2	1	1	2	0	1	2	1	2	2	2	1	17
Hsiao et al., 2015	2	2	1	2	0	2	2	1	2	2	2	1	19
Takahashi et al., 2015	2	2	1	2	0	2	1	1	2	2	1	1	17
Piessen et al., 2015	2	1	1	2	0	2	2	1	2	2	2	1	18
Xue et al., 2015	2	2	1	2	0	2	2	1	2	2	0	1	17
Khoo et al., 2017	2	2	1	2	0	2	2	1	2	1	1	1	17
Qiu et al., 2017	2	1	1	2	0	2	2	1	2	2	2	1	18
Lian et al., 2017	2	1	1	2	0	2	2	1	2	2	2	1	18

Study or Subgroup	Laparoscopic Surgery			Open Surgery				Mean Difference
Study or Subgroup	Mean (cm)	SD (cm)	Total	Mean (cm)	SD (cm)	Total	Weight (%)	IV, Fixed, 95%CI	Year
Kim et al. 2012	6.1	1.3	24	7.2	1.7	14	12.6	- 1.10 [-2.13, -0.07]	2012
Hsiao et al. 2015	6.3	1.1	18	6	0.9	21	32.8	0.30 [-0.34, 0.94]	2014
Lin et al. 2014	7.2	1.6	23	7.3	1.5	23	16.6	-0.10 [-1.00, 0.80]	2014
Takahashi et al. 2015	6.025	0.79	12	8.325	5.17	15	1.9	-2.30 [-4.95, 0.35]	2015
Khoo et al. 2017	7.04	1.5	23	7.53	1.875	36	17.8	-0.49 [-1.36, 0.38]	2016
Qiu et al. 2017	7	1.4	24	7.6	1.75	24	16.6	-0.60 [-1.50, 0.30]	2017
Lian et al. 2017	6.5	3.33	11	6.5	3.33	11	1.7	0.00 [-2.78, 2.78]	2017
Total (95%CI)			135			144	100.0	-0.29 [-0.65, 0.08]

(A)
Study or Subgroup	Laparoscopic Surgery			Open Surgery				Mean Difference
Study or Subgroup	Mean (min)	SD (min)	Total	Mean (min)	SD (min)	Total	Weight(%)	IV, Random, 95%CI	Year
Kim et al. 2012	119.8	62.2	24	154.3	53.5	14	12.0	-34.50 [-71.98, 2.98]	2012
Hsiao et al. 2015	146.6	50.2	18	113.3	42.9	21	12.8	33.30 [3.73, 62.87]	2014
Lin et al. 2014	124.1	50.3	23	196.5	64.8	23	12.4	-72.40 [-105.92, -38.88]	2014
Takahashi et al. 2015	123.75	44.75	12	119.5	44.22	15	12.4	4.25 [-29.54, 38.04]	2015
Xue et al. 2015	128.9	38.2	19	106	39.2	62	13.6	22.90 [3.15, 42.65]	2015
Khoo et al. 2017	210	81.25	23	105	48.75	36	12.1	105.00 [68.17, 141.83]	2016
Lian et al. 2017	197.46	59.774	13	129.23	56	13	11.2	68.23 [23.71, 112.75]	2017
Qiu et al. 2017	131	44	24	103	30	24	13.5	28.00 [6.69, 49.31]	2017
Total (95%CI)			156			208	100.0	18.90 [-13.19, 51.00]
Heterogeneity: Tau²=1868.63; ChI²=64.49, df=7 (p<0.00001); I²=89%.
Test for overall effect: Z=1.15 (p=0.25).
SD: standard deviation. CI: confidence interval.

(B)
Study or Subgroup	Laparoscopic Surgery			Open Surgery				Mean Difference
Study or Subgroup	Mean (min)	SD (min)	Total	Mean (min)	SD (min)	Total	Weight(%)	IV, Random, 95%CI	Year
Hsiao et al. 2015	42.2	40.7	18	51.4	58.4	21	20.0	-9.20 [-40.46, 22-06]	2014
Lin et al. 2014	35.6	28.3	23	127.8	116.8	23	13.4	-92.20 [-141.32, -43.08]	2014
Takahashi et al. 2015	202.5	244.65	12	255	262.69	15	1.5	-52.50 [-244.42, 139.42]	2015
Xue et al. 2015	34.1	26.5	19	60.4	60.4	62	25.3	-26.30 [-45.48, -7.12]	2015
Khoo et al. 2017	78.26	75	23	125	128.47	36	12.8	-50.21 [-101.27, 0.85]	2016
Qiu et al. 2017	73	36	24	51	105	24	22.7	-32.00 [-56.98, -7.02]	2017
Lian et al. 2017	207.5	175.86	13	86.84	105	13	4.4	102.50 [-4.12, 209.12]	2017
Total (95%CI)			132			194	100.0	-30.82 [-54.93, -6.71]
Heterogeneity: Tau²=503.33; ChI²=14.60, df=6 (p=0.02); I²=59%.
Test for overall effect: Z=2.51 (p=0.01).
SD: standard deviation. CI: confidence interval.

(A)
Study or Subgroup	Laparoscopic Surgery			Open Surgery				Mean Difference
Study or Subgroup	Mean (days)	SD (days)	Total	Mean (days)	SD (days)	Total	Weight(%)	IV, Fixed, 95%CI	Year
Lin et al. 2014	2.3	1.5	23	3.5	2.3	23	7.0	-1.20 [-2.32, -0.08]	2014
Khoo et al. 2017	2.25	0.75	23	3	1.25	36	34.0	-0.75 [-1.26, -0.24]	2016
Qiu et al. 2017	3.2	0.6	24	3.6	0.8	24	55.3	-0.40 [-0.80, 0.00]	2017
Lian et al. 2017	4.77	1.48	13	4.23	2.45	13	3.7	0.54 [-1.02, 2.10]	2017
Total (95%CI)			83			96	100.0	-0.54 [-0.84, -0.24]
Heterogeneity: ChI²=4.30, df=3 (p=0.23); I²=30%.
Test for overall effect: Z=3.56 (p=0.0004).

(B)
Study or Subgroup	Laparoscopic Surgery			Open Surgery				Mean Difference
Study or Subgroup	Mean (days)	SD (days)	Total	Mean (days)	SD (days)	Total	Weight (%)	IV, Fixed, 95%CI	Year
Lin et al. 2014	1.9	1.2	23	3	1	23	17.4	-1.10 [-1.74, -0.46]	2014
Xue et al. 2015	3.5	1.4	19	3.9	1	62	15.5	-0.40 [-1.08, 0.28]	2015
Qiu et al. 2017	2.2	0.5	24	2.5	0.7	24	59.9	-0.30 [-0.64, 0.04]	2017
Lian et al. 2017	3.69	0.75	13	3.92	1.66	13	7.2	-0.23 [-1.22, 0.76]	2017
Total (95%CI)			79			122	100.0	-0.45 [-0.72, -0.18]
Heterogeneity: ChI²=4.92, df=3 (p=0.18); I²=39%.
Test for overall effect: Z=3.31 (p=0.0009).

(C)
Study or Subgroup	Laparoscopic Surgery			Open Surgery				Mean Difference
Study or Subgroup	Mean (days)	SD (days)	Total	Mean (days)	SD (days)	Total	Weight (%)	IV, Random, 95%CI	Year
Kim et al. 2012	4.8	1.8	24	9.2	3.2	14	14.6	-4.40 [-6.22, -2.58]	2012
Hsiao et al. 2015	8.4	2.9	18	9.6	2.4	21	15.5	-1.20 [-2.80, 0.49]	2014
Lin et al.2014	7.2	1.6	23	10.1	2.6	23	17.6	-2.90 [-4.15, -1.65]	2014
Takahashi et al. 2015	14.25	7.46	12	18.25	8.01	15	4.0	-4.00 [-9.85, 1.85]	2015
Xue et al. 2015	7.2	3.8	19	9	4.8	62	13.6	-1.80 [-3.88, 0.28]	2015
Khoo et al. 2017	21.22	17.5	23	21.12	15	36	2.0	0.10 [-8.57, 8.77]	2016
Lian et al. 2017	7.92	2.66	13	6.69	1.93	13	15.0	1.23 [-0.56, 3.02]	2017
Qiu et al. 2017	6.6	2.2	24	8.1	2.3	24	17.5	-1.50 [-2.77, -0.23]	2017
Total (95%CI)			156			208	100.0	-1.83 [ [-3.12, -0.53]
Heterogeneity: Tau²2. Antonakis PT, Ashrafian H, Isla AM. Laparoscopic gastric surgery for cancer: where do we stand? World J Gastroenterol. 2014;20(39):14280-91. https://doi.org/10.3748/wjg.v20.i39.14280 https://doi.org/10.3748/wjg.v20.i39.1428... =2.08; ChI²=23.21, df=7 (p=0.002); I²=70%.
Test for overall effect: Z=2.77 (p=0.006).

(D)
Study or Subgroup	Laparoscopic Surgery		Open Surgery			Risk Ratio
Study or Subgroup	Events	Total	Events	Total	Weight (%)	IV, Fixed, 95%CI	Year
Kim et al. 2012	1	24	0	14	2.6	1.80 [0.08, 41.42]	2012
Lin et al. 2014	2	23	3	23	8.9	0.67 [0.12, 3.62]	2014
Piessen et al. 2015	11	90	21	93	56.9	0.54 [0.28, 1.06]	2015
Takahashi et al. 2015	1	12	1	15	3.6	1.25 [0.09, 17.98]	2015
Khoo et al. 2017	2	23	5	36	10.6	0.63 [0.13, 2.96]	2016
Qiu et al. 2017	3	24	5	24	14.8	0.60 [0.16, 2.23]	2017
Lian et al. 2017	1	13	0	13	2.6	3.00 [0.13, 67.51]	2017
Total (95%CI)		209			218	100.0	0.63 [0.38, 1.05]
Heterogeneity: ChI²=1.86, df=6 (p=0.93); I²=0%.
Test for overall effect: Z=1.78 (p=0.08).
SD: standard deviation. CI: confidence interval.

(A)
Study or Subgroup	Laparoscopic Surgery		Open Surgery			Risk Ratio
Study or Subgroup	Events	Total	Events	Total	Weight (%)	IV, Fixed, 95%CI	Year
Kim et al. 2012	1	24	4	14	9.9	0.15 [0.02, 1.18]	2012
Hsiao et al. 2015	1	18	0	21	4.4	3.47 [0.15, 80.35]	2014
Lin et al. 2014	3	23	5	23	25.2	0.60 [0.16, 2.22]	2014
Piessen et al. 2015	5	90	7	93	35.0	0.74 [0.24, 2.24]	2015
Takahashi et al. 2015	1	12	2	15	8.3	0.63 [0.06, 6.09]	2015
Khoo et al. 2017	0	23	2	36	4.8	0.31 [0.02, 6.15]	2016
Qiu et al. 2017	1	24	2	24	7.9	0.50 [0.05, 5.15]	2017
Lian et al. 2017	0	13	1	13	4.5	0.33 [0.01, 7.50]	2017
Total (95%CI)		227		239	100.0	0.57 [ 0.29, 1.09]
Heterogeneity: ChI²=3.41, df=7 (p=0.84); I²=0%.
Test for overall effect: Z=1.70 (p=0.09).

(B)
Study or Subgroup	Laparoscopic Surgery		Open Surgery			Risk Ratio
Study or Subgroup	Events	Total	Events	Total	Weight (%)	M-H, Fixed, 95%CI	Year
Kim et al. 2012	24	24	14	14	25.1	1.00 [0.90, 1.12]	2012
Hsiao et al. 2015	17	18	19	21	24.3	1.04 [0.87, 1,25]	2014
Qiu et al. 2017	23	24	23	24	31.9	1.00 [0.89, 1.13]	2017
Lian et al. 2017	13	13	13	13	18.7	1.00 [0.87, 1.15]	2017
Total (95%CI)		79		72	100.0	1.01 [0.94, 1.08]
Heterogeneity: ChI²=0.21, df=3 (p=0.98); I²=0%.
Test for overall effect: Z=0.30 (p=0.76).
SD: standard deviation. CI: confidence interval.

(A)
Study or Subgroup	Laparoscopic Surgery			Open Surgery				Mean Difference
Study or Subgroup	Mean (min)	SD (min)	Total	Mean (min)	SD (min)	Total	Weight(%)	IV, Random, 95%CI	Year
2.11 Wedge Resection
Hsiao et al. 2015	146.6	50.2	18	113.3	42.9	21	12.8	33.30 [3.73, 62.87]	2014
Takahashi et al. 2015	123.75	44.75	12	119.5	44.22	15	12.4	4.25 [-29.54, 38.04]	2015
Khoo et al. 2017	210	81.25	23	105	48.75	36	12.1	105.00 [68.17, 141.83]	2016
Subtotal (95%CI)			53			72	37.2	46.93 [-8.03, 101.90]
Heterogeneity: Tau²=2067.81; ChI²=16.35; df=2 (p=0.0003); I²=88%.
Test for overall effect: Z=1.67 (p=0.09).
All Surgeries
Kim et al. 2012	119.8	62.2	24	154.3	53.5	14	12.0	-34.50 [-71.98, 2.98]	2012
Lin et al. 2014	124.1	50.3	13	196.5	64.8	23	12.4	-72.40 [-105.92, -38.88]	2014
Xue et al. 2015	128.9	38.2	19	106	39.2	62	13.6	22.90 [3.15, 42.65]	2015
Qiu et al. 2017	131	44	24	103	30	24	13.5	28.00 [6.69, 49.31]	2017
Lian et al. 2017	197.46	59.774	23	129.23	56	13	11.2	68.23 [23.71, 112.75]	2017
Subtotal (95%CI)			103			136	62.8	2.30 [-38.11, 42.71]
Heterogeneity: Tau²=1857.86; ChI²=39.57, df=4 (p<0.00001); I²=90%.
Test for overall effect: Z=0.11 (p=0.91).
Total (95%CI)			156			208	100.0	18.90 [-13.19, 51.99]
Heterogeneity: Tau²=1868.63; ChI²=64.49, df=7 (p<0.00001); I²=89%.
Test for overall effect: Z=1.15 (p=0.25).
Test for subgroup differences: ChI²=1.64, df=1 (p=0.20); I²=39.2%.

(B)
Study or Subgroup	Laparoscopic Surgery			Open Surgery				Mean Difference
Study or Subgroup	Mean (mL)	SD (mL)	Total	Mean (mL)	SD (mL)	Total	Weight (%)	IV, Random, 95%CI	Year
2.11 Wedge Resection
Hsiao et al. 2015	42.2	40.7	18	51.4	58.4	21	20.0	-9.20 [-40.46, 22.06]	2014
Takahashi et al. 2015	202.5	244.65	12	255	262.69	15	1.5	-52.50 [-244.42, 139.42	2015
Khoo et al. 2017	78.26	75	23	128.47	125	36	12.8	-50.21 [-101.27, 0.85]	2016
Subtotal (95%CI)			53			72	34.3	-20.99 [-47.40, 5.42]
Heterogeneity: Tau²=0.00; ChI²=1.91; df=2 (p=0.39); I²=0%.
Test for overall effect: Z=1.56 (p=0.12).
All Surgeries
Lin et al. 2014	35.6	28.3	23	127.8	116.8	23	13.4	-92.20 [-141.32, -43.08]	2014
Xue et al. 2015	34.1	26.5	19	60.4	60.4	62	25.3	-26.30 [-45.48, -7.12]	2015
Qiu et al. 2017	73	36	24	105	51	24	22.7	-32.00 [-56.98, -7.02]	2017
Lian et al. 2017	207.5	175.86	13	105	86.84	13	4.4	102.50 [-4.12, 209.12]	2017
Subtotal (95%CI)			79			122	65.7	-31.66 [-68.04, 4.71]
Heterogeneity: Tau²=881.71; ChI²=12.22, df=3 (p=0.007); I²=75%.
Test for overall effect: Z=1.71 (p=0.09).
Total (95%CI)			132			194	100.0	-30.82 [-54.93, -6.71]
Heterogeneity: Tau²=503.33; ChI²=14.60, df=6 (p=0.02); I²=59%.
Test for overall effect: Z=2.51 (p=0.01).
Test for subgroup differences: ChI²=0.22, df=1 (p=0.64); I²=0%.

(C)
Study or Subgroup	Laparoscopic Surgery			Open Surgery				Mean Difference
Study or Subgroup	Mean (days)	SD (days)	Total	Mean (days)	SD (days)	Total	Weight (%)	IV, Random, 95%CI	Year
2.11 Wedge Resection
Hsiao et al. 2015	8.4	2.9	18	9.6	2.4	21	15.5	-1.20 [-2.89, 0.49]	2014
Takahashi et al. 2015	14.25	7.46	12	18.25	8.01	15	4.0	-4.00 [-9.85, 1.85]	2015
Khoo et al. 2017	21.22	17.5	23	21.12	15	36	2.0	0.10 [-8.57, 8.77]	2016
Subtotal (95%CI)			53			72	21.5	-1.36 [-2.96, 0.23]
Heterogeneity: Tau²=0.00; ChI²=0.93; df=2 (p=0.63); I²=0%.
Test for overall effect: Z=1.68 (p=0.09).
All Surgeries
Kim et al. 2012	4.8	1.8	24	9.2	3.2	14	14.8	-4.40 [-6.22, -2.58]	2012
Lin et al. 2014	7.2	1.6	13	10.1	2.6	23	17.6	-2.90 [-4.15, -1.65]	2014
Xue et al. 2015	7.2	3.8	19	9	4.8	62	13.6	-1.80 [-3.88, 0.28]	2015
Lian et al. 2017	7.92	2.66	13	6.69	1.93	13	15.0	1.23 [-0.56, 3.02]	2017
Qiu et al. 2017	6.6	2.2	24	8.1	2.3	24	17.5	-1.50 [-2.77, -0.23]	2017
Subtotal (95%CI)			103			136	78.5	-1.89 [-3.55, -0.23]
Heterogeneity: Tau²=2.88; ChI²=21.82, df=7 (p=0.0002); I²=82%.
Test for overall effect: Z=2.23 (p=0.03).
Total (95%CI)			156			208	100.0	-1.83 [-3.12, -0.53]
Heterogeneity: Tau²=2.08; ChI²=23.21, df=7 (p=0.002); I²=70%.
Test for overall effect: Z=2.77 (p=0.006).
Test for subgroup differences: ChI²=0.20, df=1 (p=0.66); I²=0%.
SD: standard deviation. CI: confidence interval.

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[1] Correspondence: Francisco Antonio Pita Araujo. E-mail: francisco.p.araujo98@gmail.com