A total of 1690 patients underwent ERCP for CBD stones from January 2014 to December 2018. Among these patients, 816 were excluded based on the exclusion criteria. After screening, 874 patients were included in our study: 79 patients who had asymptomatic CBD stones and 795 patients who had symptomatic CBD stones. PSM was then conducted at a ratio of 1:4, and consequently 79 patients from asymptomatic CBD group and 316 patients from the symptomatic CBD stones group were identified (Fig. 1).
Patients Characteristics
Before PSM, the proportions of the female (51 (64.6%) vs 412 (51.8%), P =0.031) and cholecystectomy history (60 (76.9%) vs 428 (54.0%), P <0.001) were significantly higher in the asymptomatic group than in the symptomatic group. Levels of prothrombin time (PT) [11.6 (10.8,12.2) vs 11.7 (11.1,12.3) seconds, P =0.020], international normalized ratio (INR) [1.0 (1.0,1.1) vs 1.0 (1.0,1.1), P =0.040], total bilirubin (TB) [13.5 (11.1,16.9) vs 21.2 (13.5,50.0) umol/L, P <0.001], alanine aminotransferase (ALT) [27.0 (17.0,46.0) vs 58.0 (24.0,138.0) IU/L, P <0.001], and aspartate transpeptidase (AST) [26.0 (20.0,35.0) vs 40.0 (25.0,100.0 IU/L), P <0.001] in the asymptomatic group was lower than those in symptomatic group. The remaining characteristics such as ages, patients’ underlying diseases, and the levels of blood cells did not differ significantly between the two groups (P >0.05). The intergroup differences between female proportion and the value of PT and INR were no longer present after PSM. But there were still significant statistical differences in the proportion of cholecystectomy and the levels of TB, ALT, and AST between the two groups (Table 1).
Table 1 Baseline characteristics of the patients
|
|
Total cohort
|
Matched cohort
|
|
Asymptomatic group (N=79)
|
Symptomatic group (N=795)
|
P
|
Asymptomatic group (N=79)
|
Symptomatic group (N=316)
|
P
|
Age (year)
|
62.6±14.7
|
59.6±16.7
|
0.086
|
62.6±14.7
|
61.8±15.4
|
0.669
|
Sex(female%)
|
51 (64.6%)
|
412 (51.8%)
|
0.031
|
51 (64.6%)
|
218 (69.0%)
|
0.450
|
Symptoms
|
|
|
|
|
|
|
Abdominal pain
|
-
|
515 (64.8%)
|
-
|
-
|
229 (72.5%)
|
-
|
Obstructive jaundice
|
-
|
227 (28.5%)
|
-
|
-
|
70 (22.2%)
|
-
|
Abdominal pain and obstructive jaundice
|
-
|
53 (6.7%)
|
-
|
-
|
17 (5.4%)
|
-
|
Underlying diseases
|
|
|
|
|
|
|
Hypertention
|
17 (21.5%)
|
173(21.8%)
|
0.960
|
17 (21.5%)
|
77 (24.4%)
|
0.595
|
Diabetes mellitus
|
10 (12.7%)
|
97(12.2%)
|
0.906
|
10 (12.7%)
|
46 (14.6%)
|
0.665
|
Ischemic heart disease
|
5 (6.3%)
|
45 (5.7%)
|
1.000
|
5 (6.3%)
|
22 (7.0%)
|
0.842
|
Cerebrovascular accident
|
2 (2.5%)
|
22 (2.8%)
|
1.000
|
2 (2.5%)
|
9 (2.8%)
|
1.000
|
Chronic kidney disease
|
2 (2.5%)
|
18 (2.3%)
|
1.000
|
2 (2.5%)
|
9 (2.8%)
|
1.000
|
Cirrhosis
|
3 (3.8%)
|
37 (4.7%)
|
0.948
|
3 (3.8%)
|
16 (5.1%)
|
0.860
|
Cholecystectomy history
|
60 (76.9%)
|
428 (54.0%)
|
<0.001
|
60 (76.9%)
|
177 (56.0%)
|
0.001
|
GS
|
|
|
0.051
|
|
|
0.113
|
CBDS with GS
|
12 (15.2%)
|
199 (25.0%)
|
-
|
12 (15.2%)
|
74 (23.4%)
|
-
|
CBDS without GS
|
67 (84.8%)
|
596 (75.0%)
|
-
|
67 (84.8%)
|
242 (76.6%)
|
-
|
Antithrombotic drug
|
2 (2.5%)
|
22 (2.8%)
|
1.000
|
2 (2.5%)
|
6 (1.9%)
|
1.000
|
Pancreatitis history
|
8 (10.1%)
|
57 (7.2%)
|
0.339
|
8 (10.1%)
|
27 (8.5%)
|
0.658
|
Billroth I reconstruction
|
0 (0.0%)
|
1 (0.1%)
|
1.000
|
0 (0.0%)
|
0 (0.0%)
|
-
|
Laboratory findings
|
|
|
|
|
|
|
Hb (g/L)
|
129.0±15.8
|
129.0±19.0
|
0.975
|
129.0±15.8
|
126.1±17.8
|
0.187
|
PLT (109/L)
|
169.4±68.1
|
177.9±76.3
|
0.373
|
169.4±68.1
|
176.8±74.3
|
0.420
|
WBC (109/L)
|
5.6±1.7
|
5.7±1.5
|
0.714
|
5.6±1.7
|
5.5±1.5
|
0.530
|
PT (s)
|
11.6 (10.8,12.2)
|
11.7(11.1,12.3)
|
0.020
|
11.6 (10.8,12.2)
|
11.7 (11.1,12.3)
|
0.051
|
INR
|
1.0 (1.0,1.1)
|
1.0 (1.0,1.1)
|
0.040
|
1.0 (1.0,1.1)
|
1.0 (1.0,1.1)
|
0.138
|
APTT (s)
|
28.7 (26.6,30.3)
|
28.6 (26.1,31.3)
|
0.586
|
28.7 (26.6,30.3)
|
28.0 (25.7,30.6)
|
0.564
|
TB (umol/L)
|
13.5 (11.1,16.9)
|
21.2 (13.5,50.0)
|
<0.001
|
13.5 (11.1,16.9)
|
18.4 (13.4,37.1)
|
<0.001
|
ALT (IU/L)
|
27.0 (17.0,46.0)
|
58.0 (24.0,138.0)
|
<0.001
|
27.0 (17.0,46.0)
|
51.0 (22.0,116.5)
|
<0.001
|
AST (IU/L)
|
26.0 (20.0,35.0)
|
40.0 (25.0,100.0)
|
<0.001
|
26.0 (20.0,35.0)
|
38.0 (24.0,80.0)
|
<0.001
|
|
|
|
|
|
|
|
|
|
|
|
GS: gallstone; CBDS: common bile duct stone; Hb: hemoglobin; PLT: plate; WBC:white blood cell; PT: prothrombin time; INR:international normalized ratio; APTT:activated partial thromboplastin time; TB:total bilirubin; ALT:alanine aminotransferase; AST: aspartate transpeptidase
Findings and procedures of ERCP
Among the included 874 patients, the findings of ERCP including presence of periampullary diverticulum (PAD), the proportion of non-dilated CBD, the number of CBD stone, and the diameter of largest stone was not significantly different between the asymptomatic and symptomatic group. Similarly, there were no significant differences in ERCP procedures including the proportion of precut sphincterotomy, difficult biliary cannulation, performed EPBD, ENBD, EST, ERBD, mechanical lithotripsy, and the proportion of patients requiring more than 30 minutes procedure time were observed between the two groups. What is more, complete stone removal in one session were no significant difference in two groups. After PSM, there was still no statistical difference in the above indicators (Table 2).
Table 2 Baseline characteristics of findings and procedures of ERCP
|
|
Total cohort
|
Matched cohort
|
|
Asymptomatic group (N=79)
|
Symptomatic group (N=795)
|
P
|
Asymptomatic group (N=79)
|
Symptomatic group (N=316)
|
P
|
PAD
|
23(29.1%)
|
228(28.6%)
|
0.935
|
23(29.1%)
|
100(31.6%)
|
0.664
|
Number of CBD stone
|
|
|
0.344
|
|
|
0.508
|
Single
|
48(60.8%)
|
439(55.2%)
|
|
48(60.8%)
|
179(56.6%)
|
-
|
Multiple(≥2)
|
31(39.2%)
|
356(44.8%)
|
|
31(39.2%)
|
137(43.4%)
|
-
|
CBDD
(<1.0cm/≥ 1.0cm)
|
17(21.5%)/
62(78.5%)
|
181(22.8%)/
614(77.2%)
|
0.800
|
17(21.5%)/
62(78.5%)
|
52(16.5%)/
264(83.5%)
|
0.289
|
Largest diameter of stone (cm)
|
1.0±0.6
|
1.1±0.6
|
0.523
|
1.0±0.6
|
1.1±0.6
|
0.647
|
Precut sphincterotomy
|
4(5.1%)
|
32(4.0%)
|
0.884
|
4(5.1%)
|
14(4.4%)
|
1.000
|
Difficult cannulation
|
17(21.5%)
|
198(24.9%)
|
0.505
|
17(21.5%)
|
63(19.9%)
|
0.754
|
EPBD
|
27(34.2%)
|
286(36.0%)
|
0.751
|
27(34.2%)
|
112(35.4%)
|
0.833
|
ENBD
|
64(81.0%)
|
677(85.2%)
|
0.328
|
64(81.0%)
|
270(85.4%)
|
0.330
|
EST
|
70(88.6%)
|
686(86.3%)
|
0.565
|
70(88.6%)
|
279(88.3%)
|
0.937
|
ERBD
|
11(13.9%)
|
85(10.7%)
|
0.381
|
11(13.9%)
|
30(9.5%)
|
0.248
|
Mechanical lithotripsy
|
29(36.7%)
|
243(30.6%)
|
0.261
|
29(36.7%)
|
99(31.3%)
|
0.361
|
Procedure time (>30min)
|
24(30.4%)
|
174(21.9%)
|
0.085
|
24(30.4%)
|
72(22.8%)
|
0.159
|
Complete stone
removal in one session
|
66(83.5%)
|
663(83.4%)
|
0.973
|
66(83.5%)
|
257(81.3%)
|
0.648
|
PAD:periampullary diverticulum; CBD: common bile duct; CBDD: diameter of common bile duct; EPBD: endoscopic papillary balloon dilation; ENBD: endoscopic nasobiliary drainage; EST: endoscopic sphincterotomy; ERBD: endoscopic retrograde biliary drainage.
|
PEP and its severity
PEP occurred in 6 patients in the asymptomatic group (6/79, 7.6%) and 55 patients in the symptomatic group (55/795, 6.9%). The incidence of PEP was not statistically different between the two groups (P=0.822). After PSM, there was still no significant difference in the incidence of PEP between the two groups (P=0.854) (Table 3).
Further analysis of the severity of PEP in the two groups revealed that all the 6 patients with PEP in the asymptomatic group were mild, and the number and proportion of patients with mild, moderate and severe PEP in the symptomatic group were 45 (81.8%), 9 (16.4%) and 1 (1.8%), respectively. There was no statistically significant difference in the severity of PEP between the two groups (P=0.258). After PSM, there was still no statistical difference in the severity of PEP between the two groups (P=0.199) (Table 3).
Table 3 Incidence and severity of PEP in all patients and matched patients
|
|
Total cohort
|
Matched cohort
|
|
Asymptomatic group (N=79)
|
Symptomatic group (N=795)
|
P
|
Asymptomatic group (N=79)
|
Symptomatic group (N=316)
|
P
|
Incidence
|
6(7.6%)
|
55(6.9%)
|
0.822
|
6(7.6%)
|
26(8.2%)
|
0.854
|
Severity
|
|
|
0.258
|
|
|
0.199
|
Mild
|
6 (100%)
|
45 (81.8%)
|
|
6 (100%)
|
20 (76.9%)
|
|
Moderate
|
0 (0.0%)
|
9 (16.4%)
|
|
0
|
6 (23.1%)
|
|
Severe
|
0 (0.0%)
|
1 (1.8%)
|
|
0
|
0 (0.0%)
|
|
ERCP related other complications and its severity
ERCP related cholangitis, bleeding and perforation was noted in 1 (1.3 %), 3(3.8%) and 0 patients in the asymptomatic group respectively. In the symptomatic group, ERCP related cholangitis, bleeding and perforation occurred in 7(0.9%), 13(1.6%) and 2 patients (0.3%), respectively. The incidence of cholangitis and bleeding in the asymptomatic group was higher than that in the symptomatic group, and the incidence of perforation was lower than that in the symptomatic group. But these differences between the two groups were not statistically different. After PSM, the incidence of cholangitis, bleeding, and perforation between the two groups had no statistical difference either (Table 4).
Table 4 Incidence and severity of other ERCP related complications in all patients and matched patients
|
|
Total cohort
|
Matched cohort
|
|
Asymptomatic group (N=79)
|
Symptomatic group (N=795)
|
P
|
Asymptomatic group (N=79)
|
Symptomatic group (N=316)
|
P
|
Incidence
|
|
|
|
|
|
|
cholangitis
|
1(1.3%)
|
7(0.9%)
|
0.533
|
1(1.3%)
|
3(0.9%)
|
1.000
|
Bleeding
|
3(3.8%)
|
13(1.6%)
|
0.354
|
3(3.8%)
|
3(0.9%)
|
0.181
|
perforation
|
0
|
2(0.3%)
|
1.000
|
0
|
2(0.6%)
|
1.000
|
Severity
|
|
|
0.098
|
|
|
0.294
|
Mild
|
4 (100%)
|
12 (54.5%)
|
|
4 (100%)
|
6 (75.0%)
|
|
Moderate
|
0 (0.0%)
|
8 (36.4%)
|
|
0 (0.0%)
|
2 (25.0%)
|
|
Severe
|
0 (0.0%)
|
2 (9.1%)
|
|
0 (0.0%)
|
0 (0.0%)
|
|
Then we compared the severity of the other complications (cholangitis, bleeding, and perforation) between two groups of patients. All 4 complications in the asymptomatic group were mild. In the symptomatic group, 12 (54.5%) complications were mild, 8 (36.4%) were moderate, 2 (9.1%) were severe. There was no statistical difference in the severity of the other complications between the two groups (P=0.098). After PSM, we found that there was still no statistical difference in the severity of complications between the two groups (P=0.294) (Table 4).