Review
Sphincterotomy plus balloon dilation versus sphincterotomy
alone for choledocholithiasis: a meta-analysis
Authors
Shou Quan Dong1, 2, Tikka Prabhjot Singh 1, 2, Qiu Zhao1, 2, Juan Juan Li1, 2, Hong Ling Wang1, 2
Institutions
1 Department of Gastroenterology, Zhongnan Hospital
of Wuhan University, Wuhan, China
2 The Hubei Clinical Center and Key Laboratory of
Intestinal and Colorectal Diseases, Wuhan, China
submitted 10.10.2017
accepted after revision 15.1.2019
Bibliography
DOI https://doi.org/10.1055/a-0848-8271
Published online: 2019 | Endoscopy
© Georg Thieme Verlag KG Stuttgart · New York
ISSN 0013-726X
Corresponding author
Hong Ling Wang, PhD, Department of Gastroenterology/
Hepatology, Zhongnan Hospital of Wuhan University,
169 Donghu Road, Wuhan, 430071, Hubei, China
Fax: +86-027-67813061
zhnwhl@whu.edu.cn
Fig. 1s – 4s, Table 1s – 5s
Online content viewable at:
https://doi.org/10.1055/a-0848-8271
Introduction
Common bile duct (CBD) stones are a common hepatobiliary
condition all around the world [1]. Along with the rapid devel-
opment of endoscopic technology, endoscopic treatments
have become an attractive therapy for the removal of CBD
stones rather than traditional surgical treatment because
endoscopic treatments are less invasive and lead to fewer com-
plications [2]. Currently, two common types of endoscopic
treatments are widely used for CBD stone removal in clinical
practice, namely, endoscopic sphincterotomy (EST) and endo-
scopic papillary balloon dilation (EPBD) [3].
Dong ShouQuan et al. EST plus balloon dilation vs. EST alone for choledocholithiasis … Endoscopy
ABSTR AC T
Background Endoscopic sphincterotomy plus balloon di-
lation (ESBD) is considered to be a promising method for
the removal of large common bile duct (CBD) stones. How-
ever, when compared with endoscopic sphincterotomy
(EST) alone, the efficacy and safety of ESBD remain contro-
versial. This meta-analysis aimed to compare the efficacy
and safety of ESBD vs. EST for the removal of large CBD
stones.
Methods Electronic databases were searched up to 15 July
Downloaded by: Macquarie University. Copyrighted material.
2018 for literature that compared ESBD with EST for the re-
moval of CBD stones. Pooled odds ratios (ORs) of the stone
clearance rate and the complication rate were used to com-
pare the efficacy and safety of ESBD vs. EST.
Results A total of 18 studies with 2789 patients were in-
cluded. The results showed that the stone removal rate
was much higher in the ESBD group than in the EST group,
both across all endoscopic retrograde cholangiopancreato-
graphy (ERCP) sessions (OR 2.68, 95 % confidence interval
[CI] 1.79 to 4.01) and during the first ERCP session (OR
2.07, 95 %CI 1.37 to 3.12). The ESBD group had fewer com-
plications than EST alone (OR 0.63, 95 %CI 0.47 to 0.85).
Moreover, the ESBD group needed less mechanical litho-
tripsy (OR 0.38, 95 %CI 0.24 to 0.61) and had a shorter
procedure time (mean difference – 4.05, 95 %CI – 7.02 to
– 1.09) than EST alone.
Conclusion The efficacy and safety of ESBD were superior
to those of EST for the removal of large CBD stones. More-
over, less mechanical lithotripsy and shorter procedure
times were needed with ESBD to manage large stones.
EST had been reported as an effective method for CBD stone
removal by several randomized controlled trials (RCTs) [4, 5],
and many clinical guidelines recommended EST as a standard
therapy for CBD stone removal [6]. However, the procedure-
related complications are also very common, including acute
pancreatitis, severe bleeding, dysfunction of the papillary mus-
cle, and perforation [7]. Therefore, EPBD was introduced as an
alternative method [8]. In a newly published meta-analysis,
EPBD was reported to have lower bleeding risk than EST. How-
ever, the efficacy of EPBD was inferior to EST, and pancreatitis
also tended to be more common in EPBD [9]. These results in-
dicate that EPBD also has its disadvantages.
 Review
To overcome the limitations of EST alone and EPBD alone,
endoscopic sphincterotomy plus endoscopic papillary balloon
dilation (ESBD) was first introduced for CBD stone removal in
2003 [10]. Subsequent studies have shown that ESBD has effi-
cient stone clearance and acceptable adverse events [11]. How-
ever, compared with EST alone, it is still unclear which proce-
dure is better, especially for the removal of large CBD stones.
The evidence provided by existing studies is weak and remains
controversial: some studies report that ESBD has similar effica-
cy and safety to EST [12], whereas others report that ESBD is
superior to EST for the removal of large CBD stones [13]. For
this reason, we searched all published studies on this topic in
electronic databases, including PubMed, EMBASE, and the Co-
chrane Library, and performed a meta-analysis to compare the
efficacy and safety of ESBD vs. EST for the removal of large CBD
stones. Moreover, we also compared the need for mechanical
lithotripsy and total procedure time between ESBD and EST
groups for CBD stone removal.
Methods
Literature search strategy
Published literature was searched through electronic databases
including PubMed, EMBASE, and the Cochrane Library, through
to 15 July 2018. The following keywords were used for the
search: “endoscopic sphincterotomy,” “balloon dilation,” and
“choledocholithiasis” or “common bile duct stone.” Additional-
ly, related or similar articles provided by the databases, as well
as citations from pertinent articles, were also considered in or-
der to broaden the search. Authors were contacted through
emails to obtain unpublished data. The literature search was
conducted independently by two reviewers (S.Q.D. and T.P.S.),
and a final confirmation was made by another reviewer (H.L.
W.).
Study selection criteria
Inclusion criteria were: 1) clinical trials comparing ESBD vs. EST
for the removal of CBD stones – both RCTs and nonrando-
mized comparative trials (NRCTs) were considered; 2) trials en-
rolling patients with large stones (diameter of the largest
stone ≥ 10 mm) or multiple stones; 3) trials confirming CBD
stones, stone size, stone number, and stone removal by endo-
scopic retrograde cholangiopancreatography (ERCP) or endo-
scopic ultrasound; 4) trials using standard methods (according
to the 1991 consensus guidelines [14]) to define early compli-
cations and to record them in detail; and 5) trials not limited in
ethnicity and language.
Exclusion criteria were: 1) case reports; 2) systematic re-
views or meta-analyses comparing ESBD vs. EPBD or EST vs.
EPBD; 2) individual trials focusing on comparing ESBD vs. EPBD
or EST vs. EPBD; 3) trials focusing on ESBD or EST or EPBD alone;
4) trials focusing on other diseases, such as pancreatic diseases;
and 5) unavailability of the full article.
Dong ShouQuan et al. EST plus balloon dilation vs. EST alone for choledocholithiasis … Endoscopy
Study quality assessment
After selection of studies, the quality of eligible trials was asses-
sed. RCTs were assessed according to the risk of bias using the
Cochrane reviewer’s handbook (Version 5.1.0). The following
items were assessed: 1) methods of random allocation genera-
tion and allocation concealment; 2) blinding of participants and
researchers; 3) blinding of the outcome assessors; 4) selective
outcome reporting; 5) attrition bias; and 6) other biases. NRCTs
were assessed according to the Newcastle-Ottawa Scale for
case – control studies. The following items were assessed:
1) definition of cases; 2) representativeness of cases; 3) selec-
tion of controls; 4) definition of controls; 5) comparability of
cases and controls; 6) determination of exposure factor;
7) whether the same method had been used to determine ex-
posure factor between case and control groups; and 8) nonre-
sponse rate of the two groups. NRCTs with total points ≥ 5 were
included.
Data extraction
Downloaded by: Macquarie University. Copyrighted material.
Data regarding the following main outcomes were extracted
from each study: 1) total stone removal rate; 2) stone removal
rate during the first ERCP session; 3) rate of procedure-related
complications; 4) frequency of mechanical lithotripsy used; and
5) procedure time. Tables, figures, supplemental materials, and
notes on the studies were used for data extraction. Data extrac-
tion was performed independently by two reviewers (Q.Z. was
responsible for RCT data extraction and J.J.L. was responsible
for NRCT data extraction), and final confirmations were made
by another reviewer (H.L.W.).
Statistical analysis
Review Manager (Version 5.3) was used for the statistical analy-
ses of the meta-analysis. We used a pooled odds ratio (OR) and
95 % confidence interval (CI) to analyze most outcomes, with
the exception of the procedure time, which was analyzed by
using pooled mean difference and 95 %CI. The chi-squared test
and Higgins I2 statistic were used to estimate the heterogenei-
ty among different studies. Heterogeneity was not considered
to be significant among the included studies when P > 0.1 and
I2 < 50 %, and the fixed effects model was used in those instan-
ces. Otherwise, heterogeneity was considered to exist and a
random effects model was used. Owing to the differences in
study type between RCTs and NRCTs, the data from both sub-
groups could be pooled only if there was not significant hetero-
geneity. In all analyses, P < 0.05 was considered statistically sig-
nificant. Additionally, funnel plots and Egger’s tests were used
to evaluate the publication bias; P ≥ 0.1 was considered to indi-
cate no significant publication bias. Sensitivity analysis was also
conducted to confirm the stability of our results.
Results
Study selection, characteristics, and quality
A total of 320 related studies were found in the PubMed, EM-
BASE, and Cochrane Library databases. After screening by re-
viewing titles, abstracts, and full texts, 18 studies were finally
 ▶ Table 1 Characteristics of included trials.

Study and Study Cen- Balloon Sample size, n Stone size 1, mm Stone no. Attempts
country type ters in- diameter, reported 2
volved mm
ESBD EST ESBD EST ESBD EST ESBD EST

Karsenti D 2017 RCT 21 12 – 20  77  73 > 13 > 13 2.8 3 3.6 3 1 1

[13], France

Guo Y 2015 RCT  1 10 – 15  85  85 > 10 > 10 43.53 % 4 48.24 % 4 1 1

[15], China

Heo JH 2007 RCT  1 12 – 20 100 100 16 3 15 3 2.7 3 2.7 3 3 3

[16], Korea

Stefanidis G 2011 RCT  1 15, 18, 20  45  45 12 – 20 12 – 20 NR NR NR NR

[17], Greece

Teoh AY 2013 RCT  2 ≤ 15  73  78 12.47 3 13.26 3 60.3 % 4 55.1 % 4 2 2

[12], China

Kim HG 2009 RCT  1 15, 16.5,  27  28 20.8 3 21.3 3 2.2 3 2.3 3 3 3
[18], Korea 18

Li G 2014 RCT  1 15, 16.5,  90  86 ≥ 12 ≥ 12 30.3 % 5 25.6 % 5 1 1

Downloaded by: Macquarie University. Copyrighted material.

[19], China 18

Jun Bo Q 2013 RCT  1 12 – 20  63  69 20.6 3 20.3 3 2.2 3 2.3 3 2 2

[20], China

Mu H 2015 RCT  1 10, 15 147 144 13.6 3 12.9 3 30.0 % 5 29.2 % 5 1 1

[21], China

Itoi T 2009 NRCT  1 15, 18, 20  53  48 14.8 3 15.3 3 3.2 3 3.0 3 2 2
[22], Japan

Guo SB 2014 NRCT  1 10 – 15  64  89 12.1 3 12.9 3 46.88 % 4 47.19 % 4 2 2

[23], China

Kim KY 2013 NRCT  1 ≥ 12 101 121 12 3 10 3 23 13 NR NR

[24], Korea

Kim TH 2011 NRCT  1 12 – 20  72  77 ≥ 10 ≥ 10 53.7 % 5 46.8 % 5 1 1

[25], Korea

Guidi MA 2015 NRCT  1 12 – 20  44  69 ≥ 20 ≥ 20 Multiple Multiple 1 1

[26], Argentina

Tsuchida K 2015 NRCT  1 NR  34  36 18.29 3 18.21 3 3.5 3 3.0 3 1 1

[27], Japan

Xu XD 2017 NRCT  1 12 – 20  73  76 16.9 3 16.5 3 2.9 3 2.3 3 1 1

[28], China

Park JS 2014 NRCT  1 10 – 18  99 207 15.7 3 13.6 3 NR NR 1 1

[29], Korea

Rosa B 2013 NRCT  1 12 – 18  68  43 16.8 16.0 70.6 % 6 48.8 % 6 1 1

[30], Portugal

ESBD, endoscopic sphincterotomy plus endoscopic papillary balloon dilation; EST, endoscopic sphincterotomy; NR, not reported; NRCT, nonrandomized compara-
tive trial; RCT, randomized controlled trial.
1
The diameter of the largest stone.
2
Number of sessions reported.
3
Mean value.
4
% of patients with > 1 stone.
5
% of patients with ≥ 3 stones.
6
Multiple stones.

included [12, 13, 15 – 30], including 9 RCTs [12, 13, 15 – 21] and total of 2789 patients with large CBD stones were included,
9 NRCTs [22 – 30] (8 retrospective studies [22 – 25, 27 – 30] and with 1315 patients in the ESBD group and 1474 patients in the
1 prospective study [26]). The detailed selection process is EST group. The detailed characteristics of all included studies
shown in Fig. 1s in the online-only Supplementary material. A are presented in ▶ Table 1.

Dong ShouQuan et al. EST plus balloon dilation vs. EST alone for choledocholithiasis … Endoscopy
 Review

ESBD EST Odds Ratio Odds Ratio

Study or Subgroup Events Total Events Total Weight M-H. fixed, 95 % CI M-H. fixed, 95 % CI
1.1.1 RCT
Kim HG 2009 27 27 28 28 Not estimable
Teoh AY 2013 71 73 78 78 8.1 % 0.18 [0.01, 3.86]
Heo JH 2007 97 100 98 100 9.3 % 0.66 [0.11, 4.04]
Jun Bo Q 2013 60 63 63 69 9.1 % 1.90 [0.46, 7.96]
Guo Y 2015 82 85 79 85 8.8 % 2.08[0.50, 8.59]
Mu H 2015 143 147 135 144 11.8 % 2.38 [0.72, 7.92]
Stefanidis G 2011 44 45 41 45 2.9 % 4.29 [0.46, 40.01]
Li G 2014 88 90 75 86 5.4 % 6.45 [1.39, 30.04]
Subtotal (95 % CI) 630 635 55.4 % 2.14 [1.22, 3.76]
Total events 612 597
Heterogeneity: Chi2 = 6.53, df = 6 (P = 0.37); I2 = 8 %
Test for overall effect: Z = 2.64 (P = 0.008)

1.1.2 NRCT
Xu XD 2017 73 73 76 76 Not estimable
Kim KY 2013 100 101 121 121 5.2 % 0.28 [0.01, 6.84]
Guo SB 2014 62 64 84 89 7.0 % 1.85 [0.35, 9.83]
Kim TH 2011 70 72 73 77 6.2 % 1.92 [0.34, 10.80]

Downloaded by: Macquarie University. Copyrighted material.

Guidi MA 2015 38 44 48 69 16.2 % 2.77 [1.02, 7.55]
Itoi T 2009 53 53 47 48 1.5 % 3.38 [0.13, 84.94]
Park JS 2014 99 99 202 207 2.1 % 5.40 [0.30, 98.72]
Rosa B 2013 65 68 30 43 5.1 % 9.39 [2.49, 35.42]
Tsuchida K 2015 34 34 32 36 1.4 % 9.55 [0.49, 184.51]
Subtotal (95 % CI) 608 766 44.6 % 3.34 [1.86, 5.99]
Total events 594 713
Heterogeneity: Chi2 = 6.25, df = 7 (P = 0.51); I2 = 0 %
Test for overall effect: Z = 4.05 (P < 0.0001)

Total (95 % CI) 1238 1401 100.0 % 2.68 [1.79, 4.01]

Total events 1206 1310
Heterogeneity: Chi2 = 13.73, df = 14 (P = 0.47); I2 = 0 % 0.002 0.1 1 10 500
Test for overall effect: Z = 4.78 (P < 0.00001) ESBD EST
Test for subgroup differences: Chi2 = 1.16, df = 1 (P = 0.28), I2 = 13.8 %
a

▶ Fig. 1 Comparison of efficacy (stone removal rate) between endoscopic sphincterotomy (EST) plus endoscopic papillary balloon dilation vs.
EST alone. a Stone removal rate across all endoscopic retrograde cholangiopancreatography (ERCP) sessions. b Stone removal rate during first
ERCP session. CI, confidence interval; ESBD, EST plus endoscopic papillary balloon dilation; M-H, Mantel-Haenszel; NRCT, nonrandomized com-
parative trial; RCT, randomized controlled trial.
(continued on following page)

According to the Cochrane reviewer’s handbook, most RCTs Efficacy

were of moderate quality and only one was of high quality (Fig.
2s). The main reasons affecting the quality of RCTs were:
1) blinding of participants and researchers was not designed
or mentioned; 2) blinding of the outcome assessors was not de-
signed or mentioned; 3) most studies included data from only
one clinical center with a small sample size, which may cause a
high selection bias; 4) follow-up information of most RCTs was
unclear or trials did not record follow-up details. However, most
NRCTs included were of moderate-to-high quality, with total
points ranging from 5 to 8 according to the Newcastle-Ottawa
Scale (Table 1s).
We first compared the total stone removal rate between the
ESBD group and the EST group. In total, 17 studies were includ-
ed, containing 8 RCTs [12, 15 – 21] and 9 NRCTs [22 – 30]. One
RCT [13] was excluded because it had a procedure crossover
after failure by EST alone. As shown in ▶ Fig. 1a, the crude total
stone removal rate was 97.4 % (95 %CI 95.6 % to 99.0 %) in the
ESBD group and 93.5 % (95 %CI 87.7 % to 95.8 %) in the EST
group, and the total pooled OR (2.68, 95 %CI 1.79 to 4.01) indi-
cated that the efficacy of ESBD was superior to that of EST
alone, with no significant heterogeneity (P = 0.47, I2 = 0 %). Ad-
ditionally, the results of the RCT subgroup (OR 2.14, 95 %CI
1.22 to 3.76) and the NRCT subgroup (OR 3.34, 95 %CI 1.86 to
5.99) were comparable, and the heterogeneity between sub-
groups was also acceptable (P = 0.28, I2 = 13.8 %).

Dong ShouQuan et al. EST plus balloon dilation vs. EST alone for choledocholithiasis … Endoscopy
 ESBD EST Odds Ratio Odds Ratio
Study or Subgroup Events Total Events Total Weight M-H. fixed, 95 % CI M-H. fixed, 95 % CI
1.2.1 RCT
Guo Y 2015 82 85 79 85 4.8 % 2.08 [0.50, 8.59]
Heo JH 2007 83 100 87 100 8.1 % 0.73 [0.33, 1.60]
Jun Bo Q 2013 51 63 42 69 8.0 % 2.73 [1.24, 6.04]
Karsenti D 2017 74 77 54 73 5.5 % 8.68 [2.44, 30.82]
Kim HG 2009 23 27 23 28 4.8 % 1.25 [0.30, 5.26]
Mu H 2015 132 147 103 144 8.9 % 3.50 [1.84, 6.68]
Teoh AY 2013 65 73 69 78 6.8 % 1.06 [0.39, 2.91]
Subtotal (95 % CI) 572 577 46.9 % 2.05 [1.10, 3.81]
Total events 510 457
Heterogeneity: Tau2 = 0.43; Chi2 = 16.99, df = 6 (P = 0.009); I2 = 65 %
Test for overall effect: Z = 2.26 (P = 0.02)

1.2.2 NRCT
Guidi MA 2015 38 44 48 69 6.8 % 2.77 [1.02, 7.55]
Guo SB 2014 58 64 79 89 6.5 % 1.22 [0.42, 3.56]
Itoi T 2009 51 53 41 48 4.1 % 4.35 [0.86, 22.10]
Kim TH 2011 63 72 57 77 7.6 % 2.46 [1.03, 5.83]
Park JS 2014 76 99 174 207 9.2 % 0.63 [0.35, 1.14]

Downloaded by: Macquarie University. Copyrighted material.

Rosa B 2013 56 68 30 43 7.4 % 2.02 [0.82, 4.98]
Tsuchida K 2015 30 34 20 36 5.6 % 6.00 [1.75, 20.59]
Xu XD 2017 69 73 64 76 5.9 % 3.23 [0.99, 10.54]
Subtotal (95 % CI) 507 645 53.1 % 2.10 [1.17, 3.77]
Total events 441 513
Heterogeneity: Tau2 = 0.43; Chi2 = 19.33, df = 7 (P = 0.007); I2 = 64 %
Test for overall effect: Z = 2.49 (P = 0.01)

Total (95 % CI) 1079 1222 100.0 % 2.07 [1.37, 3.12]

Total events 951 970
Heterogeneity: Tau2 = 0.39; Chi2 = 37.16, df = 14 (P = 0.0007); I2 = 62 % 0.05 0.2 1 5 20
Test for overall effect: Z = 3.46 (P = 0.0005) ESBD EST
Test for subgroup differences: Chi2 = 0.00, df = 1 (P = 0.95), I2 = 0 %
b

▶ Fig. 1 (Continuation)

Next, we compared the rate of stone removal during the first
ERCP session. A total of 15 studies were included, containing 7
RCTs [12, 13, 15, 16, 18, 20, 21] and 8 NRCTs [22, 23, 25 – 30].
Three studies [17, 19, 24] were excluded because they did not
report the data on the outcome. As shown in ▶ Fig. 1b, our
meta-analysis revealed that the crude rate of stone removal
during the first ERCP session was 88.1 % (95 %CI 84.9 % to
91.5 %) in the ESBD group and 79.4 % (95 %CI 71.8 % to 84.0 %)
in the EST group. The results indicated that ESBD was signifi-
cantly superior to EST (pooled OR 2.07, 95 %CI 1.37 to 3.12)
for CBD stone removal during the first ERCP session. Addition-
ally, the pooled OR of the RCT subgroup (2.05, 95 %CI 1.10 to
3.81) was consistent with that of the NRCT subgroup (2.10,
95 %CI 1.17 to 3.77), and there was no significant heterogenei-
ty between the two subgroups (P = 0.95, I2 = 0 %).
Several subgroup analyses were conducted to investigate
the influence of stone size, stone number, and method of EST
performed in the ESBD group on the stone removal rate. The re-
sults indicated that the efficacy of ESBD was significantly super-
ior to that of EST in patients with a stone size ≥ 10 mm (pooled
OR 3.19, 95 %CI 1.73 to 5.88) or in patients with stone numbers
≥ 3 (pooled OR 5.23, 95 %CI 1.20 to 22.72). However, ESBD only
had a tendency to be superior to EST in patients with a stone
size ≥ 15 mm, without statistical significance (pooled OR 2.07;
95 %CI 0.94 to 4.57). Moreover, the efficacy of small incisions
(limited to one-third of the diameter of the papilla) in the
ESBD group appeared to be superior to EST alone (pooled OR
2.35, 95 %CI 1.24 to 4.46), as shown in Fig. 3s.
Safety
In total, 16 studies [12, 13, 15 – 17, 20 – 30] were used to com-
pare the rate of early complications between ESBD and EST
groups. As shown in ▶ Fig. 2, the results of our meta-analysis
showed that the ESBD group had a lower rate of early compli-
cations compared with the EST group (total pooled OR 0.63,
95 %CI 0.47 to 0.85), with no significant heterogeneity (P =
0.89, I2 = 0 %). Additionally, the trends of pooled ORs of the
RCT subgroup (0.61, 95 %CI 0.39 to 0.93) and the NRCT sub-
group (0.66, 95 %CI 0.43 to 1.00) seemed similar, with no sig-
nificant heterogeneity between the two subgroups (P = 0.80,
I2 = 0 %).

Dong ShouQuan et al. EST plus balloon dilation vs. EST alone for choledocholithiasis … Endoscopy
 Review

ESBD EST Odds Ratio Odds Ratio

Study or Subgroup Events Total Events Total Weight M-H. fixed, 95 % CI M-H. fixed, 95 % CI
1.3.1 RCT
Guo Y 2015 5 85 4 85 3.4 % 1.27 [0.33, 4.88]
Heo JH 2007 5 100 7 100 6.1 % 0.70 [0.21, 2.28]
Jun Bo Q 2013 5 63 8 69 6.4 % 0.66 [0.20, 2.13]
Karsenti D 2017 4 74 3 54 3.0 % 0.97 [0.21, 4.53]
Mu H 2015 11 147 19 144 16.2 % 0.53 [0.24, 1.16]
Stefanidis G 2011 2 45 9 45 7.8 % 0.19 [0.04, 0.92]
Teoh AY 2013 5 73 8 78 6.6 % 0.64 [0.20, 2.06]
Subtotal (95 % CI) 587 575 49.5 % 0.61 [0.39, 0.93]
Total events 37 58
Heterogeneity: Chi2 = 3.80, df = 6 (P = 0.70); I2 = 0 %
Test for overall effect: Z = 2.28 (P = 0.02)

1.3.2 NRCT
Guidi MA 2015 3 44 3 69 2.0 % 1.61 [0.31, 8.36]
Guo SB 2014 3 64 6 89 4.4 % 0.68 [0.16, 2.83]
Itoi T 2009 2 53 3 48 2.8 % 0.59 [0.09, 3.68]
Kim KY 2013 4 101 5 121 4.0 % 0.96 [0.25, 3.66]
Kim TH 2011 6 72 10 77 8.1 % 0.61 [0.21, 1.77]

Downloaded by: Macquarie University. Copyrighted material.

Park JS 2014 2 99 8 207 4.6 % 0.51 [0.11, 2.46]
Rosa B 2013 10 68 5 43 4.8 % 1.31 [0.42, 4.13]
Tsuchida K 2015 3 34 9 36 7.3 % 0.29 [0.07, 1.18]
Xu XD 2017 8 73 16 76 12.7 % 0.46 [0.18, 1.16]
Subtotal (95 % CI) 608 766 50.5 % 0.66 [0.43, 1.00]
Total events 41 65
Heterogeneity: Chi2 = 4.82, df = 8 (P = 0.78); I2 = 0 %
Test for overall effect: Z = 1.98 (P = 0.05)

Total (95 % CI) 1195 1341 100.0 % 0.63 [0.47, 0.85]

Total events 78 123
Heterogeneity: Chi2 = 8.66, df = 15 (P = 0.89); I2 = 0 % 0.02 0.1 1 10 50
Test for overall effect: Z = 3.01 (P = 0.003) ESBD EST
Test for subgroup differences: Chi2 = 0.06, df = 1 (P = 0.80), I2 = 0 %

▶ Fig. 2 Comparison of safety between endoscopic sphincterotomy (EST) plus endoscopic papillary balloon dilation vs. EST alone. CI, confidence
interval; ESBD, EST plus endoscopic papillary balloon dilation; M-H, Mantel-Haenszel; NRCT, nonrandomized comparative trial; RCT, randomized
controlled trial.

To further compare the differences in complication rates, we
analyzed four common complications, including pancreatitis,
significant bleeding, acute cholangitis, and perforation. The re-
sults showed no significant differences between the two
groups in the rates of these complications, except for the rate
of significant bleeding, which was lower in the ESBD group
compared with the EST group (pooled OR 0.35, 95 %CI 0.17 to
0.73), as shown in Table 2s.
Mechanical lithotripsy use
A total of 15 studies [12, 13, 15, 16, 18, 20 – 24, 26 – 30] were in-
cluded to assess the frequency of mechanical lithotripsy during
the procedures. As shown in ▶ Fig. 3, mechanical lithotripsy was
used less frequently in the ESBD group compared with the EST
group (pooled OR 0.38, 95 %CI 0.24 to 0.61) by using a random
effects model (P < 0.001, I2 = 70 %). Results of both the RCT sub-
group (pooled OR 0.35, 95 %CI 0.18 to 0.68) and the NRCT sub-
group (pooled OR 0.41, 95 %CI 0.22 to 0.78) also indicated that
the ESBD group needed less mechanical lithotripsy when com-
pared with the EST group, with no significant heterogeneity be-
tween the two subgroups (P = 0.72, I2 = 0 %).
Procedure time
Seven studies [12, 15, 18, 20 – 22, 28] contained adequate infor-
mation from which to compare the procedure times between
ESBD and EST groups. As shown in ▶ Fig. 4, although trends in
the RCT subgroup showed that there was no significant differ-
ence between the two groups (pooled mean difference – 3.07,
95 %CI – 6.70 to 0.56), the results of the NRCT subgroup
(pooled mean difference – 6.41, 95 %CI – 9.70 to – 3.12])
and the total pooled mean difference (– 4.05, 95 %CI – 7.02
to – 1.09) showed that the ESBD group had a shorter procedure
time than the EST group, with a low level of heterogeneity (P =
0.18, I2 = 43.8 %).

Dong ShouQuan et al. EST plus balloon dilation vs. EST alone for choledocholithiasis … Endoscopy
 ESBD EST Odds Ratio Odds Ratio
Study or Subgroup Events Total Events Total Weight M-H. fixed, 95 % CI M-H. fixed, 95 % CI
1.4.1 RCT
Guo Y 2015 7 85 8 85 6.9 % 0.86 [0.30, 2.50]
Heo JH 2007 8 100 9 100 Not estimable
Jun Bo Q 2013 5 63 17 69 6.9 % 0.26 [0.09, 0.76]
Karsenti D 2017 3 77 26 73 6.1 % 0.07 [0.02, 0.26]
Kim HG 2009 9 27 9 28 6.6 % 1.06 [0.34, 3.26]
Mu H 2015 19 147 61 144 9.3 % 0.20 [0.11, 0.36]
Teoh AY 2013 21 73 36 78 8.9 % 0.47 [0.24, 0.92]
Subtotal (95 % CI) 472 477 44.7 % 0.35 [0.18, 0.68]
Total events 64 157
Heterogeneity: Tau2 = 0.48; Chi2 = 16.88, df = 5 (P = 0.005); I2 = 70 %
Test for overall effect: Z = 3.05 (P = 0.002)

1.4.2 NRCT
Guo SB 2014 3 64 7 89 5.5 % 0.58 [0.14, 2.32]
Itoi T 2009 3 53 12 48 5.7 % 0.18 [0.05, 0.68]
Kim KY 2013 25 101 33 121 9.2 % 0.88 [0.48, 1.60]
Kim TH 2011 6 72 15 77 7.2 % 0.38 [0.14, 1.03]
Park JS 2014 12 99 18 207 8.4 % 1.45 [0.67, 3.14]

Downloaded by: Macquarie University. Copyrighted material.

Rosa B 2013 10 68 16 43 7.7 % 0.29 [0.12, 0.72]
Tsuchida K 2015 17 34 34 36 4.8 % 0.06 [0.01, 0.28]
Xu XD 2017 5 73 14 76 6.9 % 0.33 [0.11, 0.96]
Subtotal (95 % CI) 564 697 55.3 % 0.41 [0.22, 0.78]
Total events 81 149
Heterogeneity: Tau2 = 0.54; Chi2 = 22.22, df = 7 (P = 0.002); I2 = 68 %
Test for overall effect: Z = 2.74 (P = 0.006)

Total (95 % CI) 1036 1174 100.0 % 0.38 [0.24, 0.61]

Total events 145 306
Heterogeneity: Tau2 = 0.51; Chi2 = 43.17, df = 13 (P < 0.0001); I2 = 70 %
0.01 0.1 1 10 100
Test for overall effect: Z = 4.08 (P < 0.0001) ESBD EST
2 2
Test for subgroup differences: Chi = 0.13, df = 1 (P = 0.72), I = 0 %

▶ Fig. 3 Comparison of mechanical lithotripsy use between endoscopic sphincterotomy (EST) plus endoscopic papillary balloon dilation vs. EST
alone. CI, confidence interval; ESBD, EST plus endoscopic papillary balloon dilation; M-H, Mantel-Haenszel; NRCT, nonrandomized comparative
trial; RCT, randomized controlled trial.

Discussion Next, we compared the total rate of early complications. The

This meta-analysis compared the efficacy of ESBD vs. EST for
the removal of large CBD stones. Several meta-analyses have
previously been published on this topic [9, 31 – 33]. Most of
them concluded that ESBD had a similar efficacy to EST [31 –
33]. However, a newly published study concluded that ESBD
was numerically superior to EST, without statistical differences
[9]. Herein, we confirmed the superiority of ESBD, with signifi-
cantly statistical differences in both the RCT and the NRCT sub-
groups, by including more RCTs and including NRCTs for the
first time. The total pooled OR also validated the superiority of
ESBD without significant heterogeneity. Moreover, we found
that the superiority of ESBD was more significant during the
first session of ERCP compared with EST alone. All results indi-
cated that it is much easier to successfully remove large CBD
stones by using ESBD. Additionally, funnel plots (see Fig. 4s)
and Egger’s tests (Table 3s) confirmed that there was no sig-
nificant publication bias for our results, and the sensitivity ana-
lyses show that all the results were stable (Table 4s).
results showed that ESBD had fewer early complications com-
pared with EST. Our conclusion differed slightly from previously
published meta-analyses, which reported that ESBD is as safe as
EST [31, 32]. For this reason, we further compared the rates of
four common early complications by conducting subgroup ana-
lyses. The results indicated that there was no significant differ-
ence between the two groups for the rates of pancreatitis,
acute cholangitis, and perforation. However, the rate of signifi-
cant bleeding was lower in the ESBD group than in the EST
group. This result was comparable to another newly published
meta-analysis [33]. As has been reported by several studies
[34, 35], less bleeding might be explained by the fact that
EPBD used during the ESBD procedure may have had a protec-
tive effect on the function of the papillary muscle.
Finally, we compared the frequency of mechanical lithotrip-
sy use and the procedure time between the ESBD group and the
EST group. The results showed that the ESBD group required
less mechanical lithotripsy and a shorter procedure time than

Dong ShouQuan et al. EST plus balloon dilation vs. EST alone for choledocholithiasis … Endoscopy
 Review

ESBD EST Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, random, 95 % CI IV, random, 95 % CI
1.5.1 RCT
Guo Y 2015 20 10 85 20 11 85 16.9 % 0.00 [–3.16, 3.16]
Jun Bo Q 2013 14.5 8.4 63 15.9 8.8 69 17.3 % -1.40 [-4.33, 1.53]
Kim HG 2009 18 12 27 19 13 28 10.2 % -1.00 [-7.61, 5.61]
Mu H 2015 39.4 15.4 147 49.4 19.6 144 15.0 % -10.00 [-14.06, -5.94]
Teoh AY 2013 24.3 12.87 73 27.2 16.9 78 13.5 % -2.90 [-7.67, 1.87]
Subtotal (95 % CI) 395 404 73.0 % -3.07 [-6.70, 0.56]
Heterogeneity: Tau2 = 12.40; Chi2 = 16.27, df = 4 (P = 0.003); I2 = 75 %
Test for overall effect: Z = 1.66 (P = 0.10)

1.5.2 NRCT
Itoi T 2009 31.6 11.3 53 40.2 16.3 48 12.1 % -8.60 [-14.12, -3.08]
Xu XD 2017 42.1 13.6 73 47.3 11.8 76 14.9 % -5.20 [-9.30, -1.10]
Subtotal (95 % CI) 126 124 27.0 % -6.41 [-9.70, -3.12]
Heterogeneity: Tau2 = 0.00; Chi2 = 0.94, df = 1 (P = 0.33); I2 = 0 %
Test for overall effect: Z = 3.82 (P = 0.0001)

Total (95 % CI) 521 528 100.0 % -4.05 [-7.02, -1.09]

Heterogeneity: Tau2 = 10.99; Chi2 = 21.09, df = 6 (P = 0.002); I2 = 72 %

Downloaded by: Macquarie University. Copyrighted material.

-20 -10 0 10 20
Test for overall effect: Z = 2.68 (P = 0.007) ESBD EST
Test for subgroup differences: Chi2 = 1.78, df = 1 (P = 0.18), I2 = 43.8 %

▶ Fig. 4 Comparison of procedure time between endoscopic sphincterotomy (EST) plus endoscopic papillary balloon dilation vs. EST alone. CI,
confidence interval; ESBD, EST plus endoscopic papillary balloon dilation; IV, inverse variance; NRCT, nonrandomized comparative trial; RCT,
randomized controlled trial; SD, standard deviation.

the EST group. This conclusion differs from previously pub-
lished meta-analyses, which indicated that no significant differ-
ence was found between the two groups when comparing me-
chanical lithotripsy use and procedure time [9, 32]. The most
reasonable explanation for the difference may be that more
studies and more patients were included in our meta-analysis.
However, significant heterogeneity existed in some of our
results, such as the comparison of mechanical lithotripsy use.
We investigated the causes of heterogeneity and found that
the major factor was a difference in CBD stone characteristics,
especially stone size and stone number. For this reason, we per-
formed subgroup analyses to clarify the influence of stone
characteristics on our results. For stone size comparison, the
results showed that the efficacy of ESBD was superior to that
of EST in patients with stone sizes ≥ 10 mm, but it only tended
to be better than EST without significantly statistical difference
when the stone size was ≥ 15 mm. For comparison of stone
number, the results indicated that the efficacy of ESBD was sig-
nificantly superior to EST for patients with ≥ 3 stones. However,
the number of studies included for the subgroup analyses were
inadequate and more studies are still needed in the future to
confirm our conclusions.
Additionally, the method of sphincterotomy used in the
ESBD group was also a possible confounding factor affecting
the results of our meta-analysis. We conducted a subgroup
analysis of patients with incisions limited to one-third of the
diameter of the duodenal papilla. The results showed that the
efficacy of ESBD was better than that of EST alone, which indi-
cated that a minor incision may be adequate for the removal of
large CBD stones by using ESBD. Indeed, the balloon size and
dilation time used in ESBD could also influence the results.
However, subgroup analyses could not be conducted because
detailed information about balloon size and dilation time used
in the ESBD group were unclear or missing (as shown in ▶ Ta-
ble 1). For this reason, it would be better to choose a balloon
size and dilation time according to the largest stone size, and a
balloon with a 12 – 20 mm diameter for a dilation time of 30 –
60 seconds will usually be adequate [36].
In conclusion, the efficacy of ESBD was superior to that of EST
for the removal of large CBD stones, both during the first ERCP
session and across all ERCP sessions. Less mechanical lithotripsy
was needed and the procedure time was shorter when ESBD was
used to remove large CBD stones. Moreover, ESBD was safer
than EST for large CBD stone removal and in particular may re-
duce the occurrence of significant bleeding. However, addition-
al well-designed, multicenter RCTs with large sample sizes are
still needed in future to confirm the superiority of ESBD.
Competing interests
None
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