3.1. Characteristics of the included studies
A total of 873 relevant English publications from various database were identified. 595 articles were filtered by titles and abstracts after duplicates removed. Then we obtained 69 articles for full-text assessment. According to the inclusion criteria, 7 PSM [24–30] studies and 1 RCT study [8] with a total of 2763 patients were finally included in this analysis. The flow diagram is showed in Fig. 1A, and Table 1 presents the individual characteristics of the selected studies. The risk of bias in PSM studies were assessed by ROBINS-I tool and present in Table 2. The risk of RCT was assessed by Cochrane risk-of-bias tool and present in Fig. 1B. The quality of evidence of every outcome was assessed by GRADE guideline and present in Table 3.
Table 1
Characteristics of included studies
Author
year
|
Design
|
Study
period
|
Volume
|
Age(mean ± SD)
|
LND
|
Reconstruction
|
RDG
|
LDG
|
RDG
|
LDG
|
Hong et al. 2016
|
PSM
|
2008–2015
|
232
|
232
|
53.7 ± 11.5
|
55.0 ± 13.0
|
D1, D1+, D2
|
BI, BII, RY
|
Li et al. 2018
|
PSM
|
2013–2017
|
66
|
66
|
55.2 ± 11.6
|
54.1 ± 11.4
|
D2
|
BI, BII
|
Li et al. 2020
|
PSM
|
2010–2019
|
516
|
516
|
54.63 ± 11.85
|
55.10 ± 10.24
|
D1, D2
|
BI, BII
|
Roh et al. 2020
|
PSM
|
2015–2017
|
51
|
51
|
58.1 ± 10.8
|
58.0 ± 11.1
|
D1+
|
BI, BII
|
Song et al. 2020
|
PSM
|
2016–2019
|
40
|
40
|
56.4 ± 12.8
|
58.1 ± 11.6
|
D2
|
BI, BII, RY
|
Ye et al. 2020
|
PSM
|
2014–2019
|
285
|
285
|
57.1 ± 8.3
|
57.0 ± 8.6
|
D2
|
BI, BII, RY
|
Isobe et al. 2021
|
PSM
|
2018–2020
|
50
|
50
|
69.2 ± 1.4
|
69.3 ± 1.4
|
D1, D1+, D2
|
BI, BII, RY
|
Lu et al. 2021
|
RCT
|
2017–2020
|
141
|
142
|
59.4 ± 10.2
|
59.3 ± 11.3
|
D1+, D2
|
BI, BII
|
BI: Billroth I; BII: Billroth II; RY: Roux-en-Y |
Table 2
Risk of bias in PSM studies (ROBINS-I)
Study
|
D1
|
D2
|
D3
|
D4
|
D5
|
D6
|
D7
|
Overall
|
Hong et al. 2016
|
low
|
moderate
|
low
|
low
|
low
|
low
|
moderate
|
moderate
|
Li et al. 2018
|
low
|
low
|
low
|
low
|
low
|
low
|
moderate
|
moderate
|
Li et al. 2020
|
low
|
moderate
|
low
|
low
|
low
|
low
|
low
|
moderate
|
Roh et al. 2020
|
low
|
low
|
low
|
low
|
low
|
low
|
moderate
|
moderate
|
Song et al. 2020
|
low
|
low
|
low
|
low
|
low
|
low
|
moderate
|
moderate
|
Ye et al. 2020
|
low
|
low
|
low
|
low
|
low
|
low
|
low
|
low
|
Isobe et al. 2021
|
low
|
moderate
|
low
|
low
|
low
|
low
|
low
|
moderate
|
Domains: |
D1: Bias due to confounding |
D2: Bias in selection of participants into the study |
D3: Bias in classification of interventions |
D4: Bias due to deviations from intended interventions |
D5: Bias due to missing data |
D6: Bias in measurement of outcomes |
D7: Bias in selection of the reported result |
Table 3
GRADE assessment for all the outcomes.
Outcomes(No. of studies)
|
Certainty assessment
|
No. of patients
|
MD (95%CI) or
OR (95%CI)
|
Risk of bias
|
Inconsistency
|
Indirectness
|
Imprecision
|
Publication bias
|
Certainty
|
Operative time (8)
|
Seriousa
|
Not serious
|
Not serious
|
Seriousb
|
None
|
Low
|
2763
|
33.22
[24.32, 42.11]
|
Blood loss (8)
|
Seriousa
|
Not serious
|
Not serious
|
Seriousb
|
None
|
Low
|
2763
|
-28.56
[-40.29, -16.83]
|
Retrieved lymph nodes (7)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
2480
|
3.46
[2.94, 3.98]
|
Time to first flatus (6)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
2199
|
-0.08
[-0.13, -0.02]
|
Time to first liquid intake (5)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
2481
|
-0.13
[-0.22, -0.05]
|
Time to start soft diet (4)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
1246
|
-0.04
[-0.31, 0.23]
|
Hospital stays (8)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
2763
|
-0.21
[-0.44, 0.01]
|
Overall complications (8)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
2763
|
0.84
[0.68, 1.04]
|
Complications Ⅰ-Ⅱ (7)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
2631
|
0.91
[0.71, 1.18]
|
Complications≥ Ⅲ (7)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
2631
|
0.70
[0.48, 1.03]
|
Anastomotic leakage (5)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
2449
|
0.73
[0.29, 1.81]
|
Bleeding (5)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
2429
|
0.89
[0.46, 1.74]
|
Intra-abdominal bleeding (3)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
1885
|
0.54
[0.20, 1.48]
|
Intraluminal bleeding (3)
|
Seriousa
|
Not serious
|
Not serious
|
Seriousb
|
None
|
Low
|
1682
|
0.84
[0.27, 2.64]
|
Ileus (5)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
2429
|
0.85
[0.39, 1.88]
|
Abdominal infection (4)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
1985
|
0.91
[0.38, 2.15]
|
Delayed gastric emptying (4)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
1033
|
0.55
[0.18, 1.66]
|
Wound complications (5)
|
Seriousa
|
Not serious
|
Not serious
|
Seriousb
|
None
|
Low
|
2429
|
1.53
[0.77, 3.05]
|
Pneumonia (5)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
2065
|
0.66
[0.41, 1.05]
|
Cardiac complications (4)
|
Seriousa
|
Not serious
|
Not serious
|
Seriousb
|
None
|
Low
|
1965
|
1.81
[0.60, 5.43]
|
Urinary infection (4)
|
Seriousa
|
Not serious
|
Not serious
|
Not serious
|
None
|
Moderate
|
1965
|
0.85
[0.27, 2.65]
|
a There may be implementation bias and measurement bias. |
b Wide range of 95% confidence intervals were identified. |
3.2. Surgical outcomes: operative time, blood loss and retrieved lymph nodes
Eight studies evaluated the operative time with a total of 1381 patients in RDG group and 1382 patients in LDG groups. Due to the high heterogeneity on operative time in the eight studies (p < 0.00001, I2 = 89%), a REM was used. The present meta-analysis showed that operative time was longer in RDG group (MD = 31.42, 95%CI= [22.88, 39.96], p < 0.00001) (Fig. 2A). Subsequently, we removed and re-entered each of these 8 studies in Review Manager 5.4 software, and found that the major reason for high heterogeneity lies with the studies of Isobe et al. 2021 and Ye et al. 2020. Because the operative time in the studies of Isobe et al. 2021 was obviously longer than other studies (350.1 ± 58.1 in RDG group, 270.5 ± 63.7 in LDG group, MD = 79.6), and a very narrow 95% CI was observed in the studies of Ye et al. 2020 (95% CI= [37.26, 40.74]). However, the statistically results in these two studies were agree with other six studies and our meta-analysis. The same result was obtained after a meta-analysis for the six studies (MD = 24.38, 95%CI= [20.66, 28.11], p < 0.00001), heterogeneity was low (p = 0.68, I2 = 0%) and analyzed in FEM (Fig. 2B).
Eight studies with a total of 2763 patients reported blood loss. Due to the moderate heterogeneity (p = 0.04, I2 = 53%), a REM was used. The present meta-analysis showed that blood loss was less in RDG group (MD=-25.89, 95%CI= [-36.18, -15.6], p < 0.00001) (Fig. 2C). The moderate heterogeneity was owing to the less blood loss in the study of Isobe et al. 2021 (12.5 ± 70.1 in RDG group, 15 ± 36.3 in LDG group, MD=-2.5) than other seven studies. Furthermore, there is no significant difference in blood loss between RGD and LDG in the study of Isobe et al. 2021 (p = 0.234), which was not consistent with other seven studies. Subsequently, a meta-analysis without the study of Isobe et al. 2021 was performed, we observed that the blood loss was still less in RDG group (MD=-26.85, 95%CI= [-32.72, -20.97], p < 0.00001). Heterogeneity was low (p = 0.11, I2 = 42%) and analyzed in FEM (Fig. 2D)
Seven studies with a total of 2480 patients reported number of retrieved lymph nodes. Our meta-analysis suggested that the RDG group retrieved more lymph nodes than LDG group (MD = 3.46, 95%CI= [2.94, 3.98], p < 0.00001). Heterogeneity was low (p = 0.24, I2 = 24%) and analyzed in FEM (Fig. 2E)
3.3. Postoperative recovery: time to first flatus, time to first liquid intake, time to start soft diet and postoperative hospital stays
Six studies with a total of 2199 patients reported time to first flatus. Our meta-analysis using a FEM (Heterogeneity: p = 0.11, I2 = 44%) revealed that time to first flatus was less in RDG group than in LDG group (MD=-0.08, 95%CI= [-0.13, -0.02], p = 0.006) (Fig. 3A). Five studies with a total of 2481 patients reported time to first liquid intake. The meta-analysis using a FEM (p = 0.12, I2 = 45%) suggested less time to first liquid intake in RDG group (MD=-0.13, 95%CI= [-0.22, -0.05], p = 0.002) (Fig. 3B). Four studies with a total of 1246 patients reported time to start soft diet. No significant difference was observed between RDG and LDG groups (MD=-0.04, 95%CI= [-0.31, 0.23], p = 0.78) after analyzed by FEM (p = 0.42, I2 = 0%) (Fig. 3C). All the studies with a total of 2763 patients reported length of postoperative hospital stays. No significant difference was observed between RDG and LDG groups (MD=-0.21, 95%CI= [-0.44, 0.01], p = 0.07) after analyzed by FEM (Heterogeneity: p = 0.91, I2 = 0%) (Fig. 3D).
3.4. Complications: overall complications, complications Grade Ⅰ-Ⅱ and complications Grade≥ Ⅲ
All the studies with a total of 2763 patients reported overall complications. No significant difference was observed between the RDG and LDG groups (OR = 0.84, 95%CI= [0.68, 1.04], p = 0.11) after analyzed by FEM (Heterogeneity: p = 0.29, I2 = 18%) (Fig. 4A). Seven studies with a total of 2631 patients stratified postoperative complications into five grades according to the Clavien-Dindo classification (CDC) [31–33]. Complications Grade Ⅰ-Ⅱ were considered as minor, Grade≥Ⅲ were considered as severe complications. The present meta-analysis revealed no statistically significant in complications Grade Ⅰ-Ⅱ (OR = 0.91, 95%CI= [0.71, 1.18], p = 0.48, heterogeneity: p = 0.13, I2 = 39%) and complications Grade≥ Ⅲ (OR = 0.70, 95%CI= [0.48, 1.03], p = 0.07, heterogeneity: p = 0.73, I2 = 0%) between RDG and LDG groups (Fig. 4B, C).
3.5. Surgical complications: anastomotic leakage, bleeding, intra-abdominal bleeding, intraluminal bleeding, ileus, abdominal infection, delayed gastric emptying and wound complications
Anastomotic leakage
Five studies with a total of 2449 patients reported anastomotic leakage. The meta-analysis indicated that there is no statistically significant between RDG and LDG groups (OR = 0.73, 95%CI= [0.29, 1.81], p = 0.49) with low heterogeneity (p = 0.42, I2 = 0%), and these were analyzed by FEM (Fig. 5A).
Bleeding, intra-abdominal bleeding and intraluminal bleeding
Of the eight studies, five, three and three studies provided data about bleeding, intra-abdominal bleeding and intraluminal bleeding, respectively. The present meta-analysis indicated that there are no statistically significant on these three items between RDG and LDG groups (OR = 0.89, 95%CI= [0.46, 1.74], p = 0.74; OR = 0.54, 95%CI= [0.20, 1.48], p = 0.23; OR = 0.84, 95%CI= [0.27, 2.64], p = 0.77). All of them were analyzed by FEM, because of low heterogeneity (p = 0.50, I2 = 0%; p = 0.75, I2 = 0%; p = 0.64, I2 = 0%) (Fig. 5B-D).
Ileus
Five studies with a total of 2429 patients reported ileus. No significant difference was observed between RDG and LDG groups (OR = 0.85, 95%CI= [0.39, 1.88], p = 0.69) after meta-analyzed by FEM (Heterogeneity: p = 0.68, I2 = 0%) (Fig. 5E).
Abdominal infection
Four studies with a total of 1985 patients reported abdominal infection. No significant difference was observed between RDG and LDG groups (OR = 0.91, 95%CI= [0.38, 2.15], p = 0.83) after meta-analyzed by FEM (Heterogeneity: p = 0.89, I2 = 0%) (Fig. 5F).
Delayed gastric emptying
Four studies with a total of 1033 patients reported delayed gastric emptying. The meta-analysis showed no difference between RDG and LDG groups (OR = 0.55, 95%CI= [0.18, 1.66], p = 0.29) with low heterogeneity (p = 0.83, I2 = 0%), and these were analyzed by FEM (Fig. 5G).
Wound complications
Five studies with a total of 2429 patients reported wound complications. The meta-analysis showed no difference between RDG and LDG groups (OR = 1.53, 95%CI= [0.77, 3.05], p = 0.23) with low heterogeneity (p = 0.67, I2 = 0%), and these were analyzed by FEM (Fig. 5H).
3.6. Systematic complications: pneumonia, cardiac complications and urinary infection
Pneumonia
Five studies with a total of 2065 patients reported the incidence rate of pneumonia. The meta-analysis suggested that RDG had a similar incidence rate of pneumonia to that of the LDG group (OR = 0.66, 95%CI= [0.41, 1.05], p = 0.08) after analyzed by FEM (Heterogeneity: p = 0.78, I2 = 0%) (Fig. 6A).
Cardiac complications
Four studies with a total of 1965 patients reported cardiac complications. No significant difference was observed between RDG and LDG groups (OR = 1.81, 95%CI= [0.60, 5.43], p = 0.29) after meta-analyzed by FEM (Heterogeneity: p = 0.91, I2 = 0%) (Fig. 6B).
Urinary infection
Four studies with a total of 1965 patients provided data about urinary infection. The present meta-analysis indicated that there was no statistically significant between RDG and LDG groups (OR = 0.85, 95%CI= [0.27, 2.65], p = 0.77). These were analyzed by FEM, because of low heterogeneity (p = 0.82, I2 = 0%) (Fig. 6C).
3.7. Publication bias
The potential role of publication bias was assessed by funnel plot. All studies lie inside the 95% CIs in the symmetrical funnel plot of postoperative hospital stays (Fig. 7A) and overall complications (Fig. 7B), indicating that there was no publication bias in these studies.