During the study period, 99 GBC patients of T2 and T3 underwent radical resection. There were 56 patients underwent LRC and 43 patients received ORC. After a 1:1 PSM, there were 30 patients in each of groups of LRC and ORC.
Baseline and pathological characteristics
In the entire cohort, there were no significant difference in the baseline characteristics including age, gender, BMI, the history of gallstone, preoperative CA199, and preoperative TB (Table 1). The incidence of elevated preoperative ALT was significantly higher in ORR group compared with LRR group (7/56 vs 14/43, P = 0.024). Regarding T stage distribution, LRR group tend to have a lower proportion of T3 stage (28/56 vs 27/43), although the difference was not statistically significant (P = 0.227). Other pathological characteristics including N stage, M stage, pathological type, tumor differentiation, peri-neural invasion, vascular invasion were comparable between LRR and ORR group.
Table 1
The comparison of baseline and pathological characteristics between LRC and ORC group
|
LRC group
(n = 56)
|
ORC group
(n = 43)
|
P
|
Age
|
|
|
|
< 60
|
15
|
17
|
0.199
|
≥ 60
|
41
|
26
|
|
Gender
|
|
|
|
Male
|
12
|
8
|
0.804
|
Female
|
44
|
35
|
|
BMI
|
|
|
|
< 24
|
38
|
27
|
0.671
|
≥ 24
|
18
|
16
|
|
Gallstone
|
|
|
|
Absence
|
29
|
26
|
0.421
|
Presence
|
27
|
17
|
|
Preoperative CA199
|
|
|
|
< 37 U/L
|
33
|
25
|
> 0.999
|
≥ 37 U/L
|
23
|
18
|
|
Preoperative TB
|
|
|
|
< 24 umolL/L
|
48
|
33
|
0.092
|
≥ 24 umolL/L
|
8
|
13
|
|
Preoperative ALT
|
|
|
|
< 40U/L
|
49
|
29
|
0.024
|
≥ 40U/L
|
7
|
14
|
|
T stage
|
|
|
|
T2
|
28
|
16
|
0.227
|
T3
|
28
|
27
|
|
N stage
|
|
|
|
N0
|
28
|
22
|
> 0.999
|
N1-N2
|
28
|
21
|
|
M stage
|
|
|
|
M0
|
53
|
40
|
> 0.999
|
M1
|
3
|
3
|
|
Pathological type
|
|
|
|
Adenocarcinoma
|
52
|
39
|
0.725
|
Squamous carcinoma
|
4
|
4
|
|
Tumor differentiation
|
|
|
|
Poor
|
23
|
16
|
0.836
|
Well or Moderate
|
33
|
27
|
|
Peri-neural invasion
|
|
|
|
Absence
|
27
|
23
|
0.686
|
Presence
|
29
|
20
|
|
Vascular invasion
|
|
|
|
Absence
|
34
|
23
|
0.541
|
Presence
|
22
|
20
|
|
Table 2
The comparison of perioperative outcomes between LRC and ORC group
|
LRC group
(n = 56)
|
ORC group
(n = 43)
|
P
|
Biliary reconstruction
|
6
|
8
|
0.384
|
Length of operation
|
292.35 ± 14.41
|
249.02 ± 13.30
|
0.033
|
Intraoperative bleeding
|
233.91 ± 26.35
|
461.25 ± 53.15
|
< 0.01
|
Lymph node yield
|
9.39 ± 0.68
|
8.26 ± 0.52
|
0.208
|
Morbidity
|
|
|
|
Bile leakage
|
6
|
3
|
0.521
|
Postoperative bleeding
|
3
|
1
|
0.448
|
Abdominal abscess
|
3
|
3
|
0.738
|
Clavien–Dindo classification grade III-IV
|
6
|
5
|
0.886
|
Days of drainage tubes indwelling
|
7.46 ± 0.62
|
9.30 ± 0.85
|
0.077
|
Postoperative days of hospital stay
|
10.32 ± 0.60
|
14.74 ± 0.91
|
< 0.01
|
Mortality at 30 postoperative days
|
1
|
1
|
0.850
|
Mortality at 90 postoperative days
|
3
|
4
|
0.527
|
Port sites metastasis
|
0
|
0
|
> 0.999
|
Perioperative outcomes and long-term survival
The incidence of biliary reconstruction was comparable between two groups. The length of operation in LRR group was significantly longer than that in ORR group (292.35 ± 14.41 vs 249.02 ± 13.30, P = 0.033). Intraoperative bleeding was significantly lower in LRR group than ORR group (233.91 ± 26.35 vs 461.25 ± 53.15, P < 0.01). Lymph node yield was comparable between two groups. Two groups also showed comparable incidence of postoperative morbidities including bile leakage, postoperative bleeding, and abdominal abscess. The incidence of Clavien–Dindo (C–D) grade III-IV was similar between groups. LRR group showed a trend of decreased days of drainage tubes indwelling (7.46 ± 0.62 vs 9.30 ± 0.85), although the difference did not show statistical significance (P = 0.077). Compared with ORR group, the postoperative days of hospital stay was significantly decreased in LRR group (10.32 ± 0.60 vs 14.74 ± 0.91, P < 0.01). Mortality at 30 postoperative days and 90 postoperative days, as well as the incidence port sites metastasis did not differ significantly between two groups. As for long-term survival, the 1-, 2-, and 3-year overall survival rates were 70.1, 50.2, and 44.6%, respectively, in the LLR group, and 52.7, 40.7, and 38.2%, respectively, in the OLR group (p = 0.155, Fig. 2A).
Baseline and pathological characteristics after PSM
After PSM, the baseline and pathological characteristics including age, gender, BMI, history of gallstone, preoperative CA199, preoperative TB, preoperative ALT, T stage, N stage, M stage, pathological type, tumor differentiation, peri-neural invasion, and vascular invasion showed good comparability between two groups as shown in Table 3.
Table 3
The comparison of baseline and pathological characteristics between LRC and ORC group after PSM
|
LRC group
(n = 30)
|
ORC group
(n = 30)
|
P
|
Age
|
|
|
|
< 60
|
9
|
11
|
0.785
|
≥ 60
|
21
|
19
|
|
Gender
|
|
|
|
Male
|
7
|
5
|
0.748
|
Female
|
23
|
25
|
|
BMI
|
|
|
|
< 24
|
21
|
20
|
> 0.999
|
≥ 24
|
9
|
10
|
|
Gallstone
|
|
|
|
Absence
|
18
|
17
|
> 0.999
|
Presence
|
12
|
13
|
|
Preoperative CA199
|
|
|
|
< 37 U/L
|
17
|
18
|
> 0.999
|
≥ 37 U/L
|
13
|
12
|
|
Preoperative TB
|
|
|
|
< 24 umolL/L
|
24
|
24
|
> 0.999
|
≥ 24 umolL/L
|
6
|
6
|
|
Preoperative ALT
|
|
|
|
< 40U/L
|
23
|
24
|
> 0.999
|
≥ 40U/L
|
7
|
6
|
|
T stage
|
|
|
|
T2
|
9
|
10
|
> 0.999
|
T3
|
21
|
20
|
|
N stage
|
|
|
|
N0
|
14
|
16
|
0.797
|
N1-N2
|
16
|
14
|
|
M stage
|
|
|
|
M0
|
29
|
29
|
> 0.999
|
M1
|
1
|
1
|
|
Pathological type
|
|
|
|
Adenocarcinoma
|
27
|
28
|
> 0.999
|
Squamous carcinoma
|
3
|
2
|
|
Tumor differentiation
|
|
|
|
Poor
|
15
|
15
|
> 0.999
|
Well or Moderate
|
15
|
15
|
|
Peri-neural invasion
|
|
|
|
Absence
|
16
|
16
|
> 0.999
|
Presence
|
14
|
14
|
|
Vascular invasion
|
|
|
|
Absence
|
17
|
17
|
> 0.999
|
Presence
|
13
|
13
|
|
Perioperative outcomes and long-term survival after PSM
Table 4 shows the perioperative outcomes of two groups after PSM. The incidence of biliary reconstruction was comparable between two groups after PSM. The length of operation in LRR group was significantly longer than that in ORR group (292.35 ± 14.41 vs 249.02 ± 13.30, P = 0.033). LRR group showed significantly decreased intraoperative bleeding (233.91 ± 26.35 vs 461.25 ± 53.15, P < 0.01). Lymph node yield, the incidence of postoperative morbidities, Clavien–Dindo (C–D) grade of III-IV, and the days of drainage tubes indwelling were comparable between groups. Postoperative days of hospital stay was significantly decreased in LRR group (10.32 ± 0.60 vs 14.74 ± 0.91, P < 0.01). Mortality at 30 postoperative days and 90 postoperative days, as well as the incidence port sites metastasis, did not differ significantly between two groups. As for long-term survival, the 1-, 2-, and 3-year overall survival rates were 61.2, 40.1, and 30.1%, respectively, in the LLR group, and 53.3, 40.1, and 40.1%, respectively, in the OLR group (p = 0.644, Fig. 2B).
Table 4
The comparison of perioperative outcomes between LRC and ORC group after PSM
|
LRC group
(n = 30)
|
ORC group
(n = 30)
|
P
|
Biliary reconstruction
|
4
|
3
|
> 0.999
|
Length of operation
|
328.12 ± 21.53
|
245.82 ± 15.18
|
< 0.01
|
Intraoperative bleeding
|
256.74 ± 39.21
|
484.36 ± 64.67
|
< 0.01
|
Lymph node yield
|
10.12 ± 0.90
|
7.92 ± 0.57
|
0.04
|
Morbidity
|
|
|
|
Bile leakage
|
3
|
2
|
0.640
|
Postoperative bleeding
|
1
|
0
|
0.313
|
Abdominal abscess
|
2
|
2
|
> 0.999
|
Clavien–Dindo Classification Grade III-IV
|
3
|
2
|
0.640
|
Days of drainage tubes indwelling
|
7.43 ± 0.71
|
8.37 ± 0.87
|
0.41
|
Postoperative days of hospital stay
|
10.43 ± 0.97
|
14.23 ± 1.07
|
0.01
|
Mortality at 30 postoperative days
|
1
|
1
|
> 0.999
|
Mortality at 90 postoperative days
|
3
|
3
|
> 0.999
|
Port sites metastasis
|
0
|
0
|
> 0.999
|
Risk factors of overall survival after operation
As shown in Table 5, univariate analysis identified T stage, N stage, vascular invasion, tumor differentiation and biliary reconstruction to be the risk factor for overall survival. Multivariate analysis further identified the T stage, vascular invasion and tumor differentiation to be the independent risk factors of overall survival for GBC of T2 and T3 stages.
Table 5
Univariable and multivariable logistic regression of factors associated with the overall survival of GBC in T2 and T3 stages
|
Univariable logistic regression
|
Multivariable logistic regression
|
|
OR (95% CI)
|
P
|
OR (95% CI)
|
P
|
Age (< 60 vs. ≥60)
|
1.354 (0.754–2.431)
|
0.310
|
|
|
Gender (Male vs. Female)
|
1.085 (0.544–2.163)
|
0.818
|
|
|
BMI (< 24 vs. ≥24)
|
0.597 (0.324–1.098)
|
0.085
|
|
|
History of Gallstone (Presence vs Absence)
|
1.476 (0.856–2.543)
|
0.162
|
|
|
CA199 (< 37 vs ≥ 37)
|
1.675 (0.965–2.845)
|
0.070
|
|
|
Total bilirubin (< 24 vs ≥ 24)
|
1.274 (0.655–2.480)
|
0.486
|
|
|
ALT (< 50 vs ≥ 50)
|
1.190 (0.636–2.225)
|
0.592
|
|
|
Surgical Type (ORR vs LRR)
|
0.678 (0.392–1.172)
|
0.162
|
|
|
T stage (T2 vs T3)
|
4.049 (2.181–7.515)
|
< 0.001
|
2.677 (1.386–5.171)
|
0.003
|
N stage (N0 vs N1-2)
|
2.368 (1.361–4.122)
|
0.002
|
1.592 (0.878–2.886)
|
0.126
|
M stage (M0 vs M1)
|
1.486 (0.535–4.130)
|
0.472
|
|
|
Vascular invasion (Presence vs Absence)
|
2.472 (1.433–4.264)
|
0.001
|
1.646 (0.912–2.971)
|
0.098
|
Neural invasion (Presence vs Absence)
|
1.228 (0.710–2.124)
|
0.463
|
|
|
Pathological type (Adenocarcinoma vs Squamous carcinoma)
|
1.629 (0.693–3.828)
|
0.292
|
|
|
Tumor differentiation (Poor vs Well or Moderate)
|
4.211 (2.365–7.499)
|
< 0.001
|
3.702 (2.021–6.781)
|
< 0.001
|
Biliary reconstruction (Presence vs Absence)
|
2.117 (1.107–4.051)
|
0.035
|
1.494 (0.770–2.900)
|
0.235
|