Introduction
Obesity is an epidemic in United States, with 35 % of adults having body mass index
(BMI) > 30 kg/m2 [1]. Indications for bariatric surgery are BMI > 40 or BMI > 30 with comorbid conditions
[2]. Roux-en-Y gastric bypass (RYGB) is the most commonly performed bariatric procedure
in the world, consisting of 47 % of the bariatric surgeries with around 200,000 surgeries
performed worldwide every year [3]
[4].
Rapid weight loss post-bariatric surgery is a risk factor for development of gallstones,
choledocholithiasis, and pancreatitis with up to 32 % to 42 % of patients developing
gallstones [5]
[6]. Obesity can also lead to increased incidence of pancreatobiliary cancers [7]. This reflects the sheer number of patients who would potentially require biliary
intervention. Endoscopic retrograde cholangiopancreatography (ERCP) in patients with
RYGB is challenging for three reasons: (1) The small bowel limb to be traversed is
very long and standard endoscopes and duodenoscopes are typically inadequate to reach
the ampulla; (2) acute angles and stenosis at the jejunostomy site decrease the success
of reaching papilla; and (3) tortuosity of the scope trajectory [8]
[9]. Various specialized procedures to perform biliary interventions in Roux-en-Y procedures
include balloon enteroscopy-assisted ERCP (BE-ERCP) (single and double), spiral enteroscopy,
laparoscopic-assisted ERCP (LA-ERCP) and gastrostomy tube-assisted ERCP.
BE-ERCP is commonly employed in this situation, however, due to inferior technical
success it is not ideal for all patients. The reasons for the lower technical success
of BE-ERCP are: (a) length of limb to be traversed; (b) absence of elevator; (c) forward
viewing endoscopic view, making it difficult to cannulate; and (d) narrow diameter
and long length of scopes making it hard to use the proper accessory instruments [8].
LA-ERCP has high technical success rates (papilla identification and cannulation)
even though it has higher complication rates [10]. However, LA-ERCP is associated with longer hospital stays, higher hospital costs,
increased complications, and requirement of multiple teams to do the procedure, all
of which are disincentives to performing biliary access via this route [11]
[12].
Endoscopic ultrasound-directed transgastric ERCP (EDGE) was first described by Kedia
et al in 2014 [13]. EDGE uses a lumen-apposing metal stent (LAMS) to create a transluminal gateway
from the gastric pouch or the proximal jejunal efferent limb to the remnant stomach
to perform ERCP using a standard duodenoscope. In studies of EDGE, it has shown to
have a high technical success rate with low risk of complications and lower hospitals
costs [14]
[15]
[16]
[17].
The aim of this study was to evaluate technical success, clinical success, and adverse
events (AEs) associated with EDGE and compare it to LA-ERCP and BE-ERCP.
Patients and methods
Search strategy
We conducted a comprehensive search of several databases and conference proceedings
including PubMed, EMBASE, Google-Scholar, LILACS, SCOPUS, and Web of Science databases
(earliest inception to February 2019). We followed the Preferred Reporting items for
Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Meta-analyses of Observational
Studies in Epidemiology (MOOSE) protocol, to identify studies reporting on EDGE procedure,
LA-ERCP, and BE-ERCP [18]
[19]. An experienced medical librarian using inputs from the study authors helped with
the literature search.
Keywords used in the literature search included a combination of ‘EDGE, ‘endoscopic,
‘ERCP’, ‘GATE’, ‘balloon’, ‘enteroscopy’ and ‘laparoscopic’. The search was restricted
to studies in human subjects and published in English language in peer-reviewed journals.
Two authors (BD, AD) independently reviewed the title and abstract of studies identified
in primary search and excluded studies that did not address the research question,
based on pre-specified exclusion and inclusion criteria. Full text of remaining articles
was reviewed to determine whether it contained relevant information. Any discrepancy
in article selection was resolved by consensus, and in discussion with a co-author.
Bibliographic section of the selected articles, as well as the systematic and narrative
articles on the topic were manually searched for additional relevant articles.
Study selection
In this meta-analysis, we included studies that evaluated performance of EDGE, LA-ERCP,
and BE-ERCP in patients with RYGB. Studies irrespective of inpatient/outpatient setting,
geography, abstract/ manuscript status, were included as long as they provided data
needed for the analysis.
The following were our exclusion criteria: (1) Alternative gastric bypass procedures
other than RYGB; (2) studies with sample size < 10 patients; (3) studies done in pediatric
population (age < 18 years); and (4) studies not published in the English language.
In cases of multiple publications from the same cohort and/or overlapping cohorts,
data from the most recent and/or most appropriate comprehensive report were included.
Data abstraction and quality assessment
Data on study-related outcomes in the individual studies were abstracted onto a standardized
form by at least three authors (BD, AD, HM), and two authors (BD, BPM) did the quality
scoring independently.
In the situation of randomized controlled trials and case-control studies, data collection
was done as number of reported events (n) out of total number of patients (N) from
each study. The collected data were treated akin to single-group cohort studies, therefore,
we used the Newcastle-Ottawa scale for cohort studies to assess the quality of studies
[20]. This quality score consisted of eight questions, the details of which are provided
in Supplementary Table 1.
Outcomes assessed
Primary outcomes
-
Pooled rate of technical success: EDGE vs LA-ERCP vs BE-ERCP.
-
Pooled rate of clinical success: EDGE vs LA-ERCP vs BE-ERCP.
Secondary outcomes
-
Pooled rate of AEs: EDGE vs LA-ERCP vs BE-ERCP.
-
Pooled rate of AE subtypes: post-ERCP pancreatitis (PEP), bleeding, perforation, stent
migration, and infection.
Assessment methodology and definitions
Collected data were matched between the groups (EDGE, LA-ERCP, BE-ERCP) before statistical
analysis. Although, this model of comparison is indirect, and the approach is comparable
to a retrospective case-control study with matched groups.
Definition of outcomes
Technical success in EDGE studies was defined as successful cannulation and deployment
placement of LAMS across the fistula and successful cannulation of the desired duct
in LA-ERCP and BE-ERCP studies.
Clinical success was defined as resolution of symptoms, laboratory investigations
and imaging via desired therapeutic maneuvers.
AEs and their severity were reported according to the American Society of Gastrointest
Endosc (ASGE) Lexicon [21].
Statistical analysis
We used meta-analysis techniques to calculate pooled estimates in each case following
the methods suggested by DerSimonian and Laird using the random-effects model [22]. When incidence of an outcome was zero in a study, a continuity correction of 0.5
was added to the number of incident cases before statistical analysis [23]. We assessed heterogeneity between study-specific estimates by using Cochrane Q
statistical test for heterogeneity, 95 % prediction interval (PI), which deals with
the dispersion of the effects, and the I2 statistics [24]
[25]. In this, values of < 30 %, 30 % to 60 %, 61 % to 75 %, and > 75 % were suggestive
of low, moderate, substantial, and considerable heterogeneity, respectively [26]. Publication bias was ascertained, qualitatively, by visual inspection of funnel
plot and quantitatively, by the Egger test [27]. When publication bias was present, further statistics using the fail-Safe N test
and Duval and Tweedie’s “Trim and Fill” test was used to ascertain the impact of the
bias [28]. Three levels of impact were reported based on concordance between the reported
results and the actual estimate if there were no bias. The impact was reported as
minimal if both versions were estimated to be same, modest if effect size changed
substantially but the final finding would still remain the same, and severe if basic
final conclusion of the analysis is threatened by the bias [29].
All analyses were performed using Comprehensive Meta-Analysis (CMA) software, version
3 (BioStat, Englewood, New Jersey, United States).
Results
Search results and population characteristics
From an initial 605 studies, 24 studies reported use of EDGE, BE-ERCP and LA-ERCP
in RYGB patients.
In our search process, we encountered studies by Irani et al [30], Kedia 2015 et al [31], Tyberg et al [32], Kedia 2019 et al [33], and Ngamruengphong et al [34] that had overlapping cohorts. The most comprehensive studies (Chiang et al [15] and Bukhari et al [35]) were included in the final analysis.
Overall, four studies [15]
[16]
[17]
[35] provided data on EDGE, 18 studies [11]
[33]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
[50]
[51] provided data on LA-ERCP, and five studies [35]
[44]
[49]
[52]
[53] provided information on BE-ERCP for our analysis.
The schematic diagram of study selection as per PRISMA guidelines and MOOSE protocol
are illustrated in Supplementary Fig. 1 and Supplementary Table 1, respectively.
Baseline population characteristics were comparable between the EDGE, LA-ERCP, and
BE-ERCP groups. Mean age was 53.72 years with a predominantly male population. Patient
demographic characteristics are described in [Table 1] and reported AEs are summarized in [Table 2].
Table 1
Description of 24 studies used in the final analysis.
|
Author
|
Type of study
|
center
|
Case-control/cohort/RCT
|
Mean age
|
Total no. patients
|
Male
|
Female
|
|
LA-ERCP
|
|
Abbas 2018 [11]
|
retrospective
|
multi
|
Cohort
|
51
|
579
|
488
|
91
|
|
Habenicht Yancey 2018 [43]
|
retrospective
|
single
|
Cohort
|
55.8
|
16
|
np
|
np
|
|
Kedia 2018 [33]
|
retrospective
|
multi
|
Case-control
|
55
|
43
|
7
|
36
|
|
Frederiksen 2017 [41]
|
retrospective
|
single
|
Cohort
|
46
|
29
|
4
|
25
|
|
May D 2017 [38]
|
retrospective
|
single
|
Cohort
|
np
|
51
|
np
|
np
|
|
Bowman 2016 [37]
|
retrospective
|
multi
|
Cohort
|
48.8
|
11
|
3
|
8
|
|
Farukhi 2016 [40]
|
retrospective
|
single
|
Cohort
|
np
|
7
|
np
|
np
|
|
Kumar 2016 [44]
|
retrospective
|
single
|
Case-control
|
51.5
|
19
|
2
|
17
|
|
Mejia 2016 [46]
|
retrospective
|
single
|
Cohort
|
51
|
4
|
2
|
2
|
|
Paranandi 2016 [47]
|
retrospective
|
single
|
Cohort
|
50.2
|
7
|
0
|
7
|
|
Grimes 2015 [42]
|
retrospective
|
single
|
Case-control
|
47.8
|
38
|
2
|
36
|
|
Snauwaert 2015 [50]
|
retrospective
|
multi
|
Cohort
|
54
|
21
|
5
|
18
|
|
Lin 2014 [45]
|
prospective
|
single
|
Cohort
|
np
|
8
|
np
|
np
|
|
Sun 2014 [51]
|
retrospective
|
single
|
Cohort
|
np
|
22
|
np
|
np
|
|
Falcão 2012 [39]
|
prospective
|
multi
|
Cohort
|
35.3
|
23
|
4
|
19
|
|
Schreiner 2012 [49]
|
retrospective
|
single
|
Case-control
|
52
|
24
|
5
|
19
|
|
Bertin 2011 [36]
|
retrospective
|
single
|
Cohort
|
np
|
22
|
np
|
np
|
|
Saleem 2010 [48]
|
retrospective
|
single
|
Cohort
|
50.8
|
15
|
3
|
12
|
|
BE-ERCP
|
|
Kashani 2018 [53]
|
retrospective
|
single
|
Cohort
|
50
|
103
|
13
|
90
|
|
Bukhari 2018 [35]
|
retrospective
|
multi
|
Case-control
|
61.8
|
30
|
12
|
18
|
|
Kumar 2016 [44]
|
retrospective
|
single
|
Case-control
|
52.1
|
12
|
1
|
11
|
|
Choi 2013 [52]
|
retrospective
|
single
|
Case-control
|
44.8
|
28
|
2
|
26
|
|
Schreiner 2012 [49]
|
retrospective
|
single
|
Case-control
|
53
|
32
|
1
|
31
|
|
Edge
|
|
Wang-2019 [17]
|
prospective
|
single
|
Cohort
|
60
|
9
|
np
|
np
|
|
Chiang 2018 [15]
|
retrospective
|
multi
|
Cohort
|
58.3
|
66
|
20
|
46
|
|
James 2018 [16]
|
retrospective
|
single
|
Cohort
|
55.5
|
19
|
4
|
15
|
|
Bukhari 2018 [35]
|
retrospective
|
multi
|
Case control
|
61.8
|
30
|
12
|
18
|
NP, not provided
Table 2
Adverse events in all procedures
|
Author
|
Total no. AE
|
Infection
|
Perforation
|
Bleeding
|
PEP
|
Stent dislodgement
|
Other
|
|
LA-ERCP
|
|
Abbas 2018 [11]
|
106
|
30
|
5
|
13
|
43
|
0
|
15
|
|
Habenicht Yancey 2018 [43]
|
1
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Kedia 2018 [33]
|
8
|
3
|
2
|
1
|
0
|
0
|
2
|
|
Frederiksen 2017 [41]
|
11
|
3
|
0
|
5
|
2
|
0
|
2
|
|
May D 2017 [38]
|
9
|
5
|
0
|
1
|
0
|
0
|
4
|
|
Bowman 2016 [37]
|
3
|
1
|
0
|
0
|
0
|
0
|
2
|
|
Farukhi 2016 [40]
|
2
|
0
|
0
|
0
|
0
|
0
|
2
|
|
Kumar 2016 [44]
|
3
|
0
|
0
|
1
|
2
|
0
|
0
|
|
Mejia 2016 [46]
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Paranandi 2016 [47]
|
2
|
1
|
0
|
0
|
1
|
0
|
0
|
|
Grimes 2015 [42]
|
5
|
np
|
np
|
np
|
np
|
0
|
np
|
|
Snauwaert 2015 [50]
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Lin 2014 [45]
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Sun 2014 [51]
|
1
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Falcão 2012 [39]
|
1
|
0
|
0
|
0
|
1
|
0
|
|
|
Schreiner 2012 [49]
|
2
|
0
|
0
|
0
|
1
|
0
|
1
|
|
Bertin 2011 [36]
|
3
|
0
|
1
|
1
|
0
|
0
|
1
|
|
Saleem 2010 [48]
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
BE-ERCP
|
|
Kashani 2018 [53]
|
13
|
1
|
2
|
0
|
10
|
0
|
0
|
|
Bukhari 2018 [35]
|
3
|
1
|
1
|
0
|
1
|
0
|
0
|
|
Kumar 2016 [44]
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Choi 2013 [52]
|
1
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Schreiner 2012 [49]
|
1
|
0
|
0
|
0
|
1
|
0
|
0
|
|
EDGE
|
|
Wang-2019 [17]
|
2
|
0
|
0
|
1
|
0
|
1
|
0
|
|
Chiang 2018 [15]
|
13
|
0
|
1
|
5
|
1
|
6
|
0
|
|
James 2018 [16]
|
7
|
0
|
0
|
0
|
0
|
6
|
1
|
|
Bukhari 2018 [35]
|
4
|
0
|
0
|
1
|
0
|
2
|
1
|
AE, adverse event; LA-ERCP, laparoscopic endoscopic retrograde cholangiopancreatography;
BE-ERCP, balloon endoscopic retrograde cholangiopancreatography; EDGE, endoscopic
ultrasound-directed transgastric retrograde cholangiopancreatography; PEP, post-ERCP
pancreatitis; NP, not provided
Characteristics and quality of included studies
Three studies were prospective, and the rest were retrospective. Seven studies were
multicenter and the rest were single-center. None were population-based. All studies
reported adequately on clinical outcomes, and assessment and factors were comparable
between the study groups. Overall, 21 studies were considered of high quality, three
were of medium quality. There were no low-quality studies. The detailed assessment
of study quality is given in [Table 3].
Table 3
Quality assessment of the study with Newcastle Ottawa Scale.
|
Author
|
Study type
|
Cohort/case-control
|
No. patients
|
Newcastle-Ottawa Scale
|
|
|
|
|
Selection
|
Comparability
|
Outcome
|
|
LA-ERCP
|
|
Abbas 2018 [11]
|
Retrospective
|
Cohort
|
579
|
***
|
*
|
***
|
|
Habenicht Yancey 2018 [41]
|
Retrospective
|
Cohort
|
16
|
***
|
*
|
***
|
|
Kedia 2018 [31]
|
Retrospective
|
Case-control
|
43
|
***
|
**
|
***
|
|
Frederiksen 2017 [39]
|
Retrospective
|
Cohort
|
29
|
***
|
*
|
***
|
|
May D 2017 [36]
|
Retrospective
|
Cohort
|
51
|
***
|
*
|
***
|
|
Bowman 2016 [35]
|
Retrospective
|
Cohort
|
11
|
***
|
*
|
**
|
|
Farukhi 2016 [38]
|
Retrospective
|
Cohort
|
7
|
**
|
*
|
*
|
|
Kumar 2016 [42]
|
Retrospective
|
Case-control
|
19
|
***
|
**
|
***
|
|
Mejia 2016 [44]
|
Retrospective
|
Cohort
|
4
|
**
|
*
|
**
|
|
Paranandi 2016 [45]
|
Retrospective
|
Cohort
|
7
|
***
|
*
|
***
|
|
Grimes 2015 [40]
|
Retrospective
|
Case-control
|
38
|
***
|
*
|
***
|
|
Snauwaert 2015 [48]
|
Retrospective
|
Cohort
|
21
|
***
|
*
|
**
|
|
Lin 2014 [43]
|
Prospective
|
Cohort
|
8
|
**
|
*
|
**
|
|
Sun 2014 [49]
|
Retrospective
|
Cohort
|
22
|
**
|
*
|
*
|
|
Falcão 2012 [37]
|
Prospective
|
Cohort
|
23
|
**
|
*
|
**
|
|
Schreiner 2012 [47]
|
Retrospective
|
Case-control
|
24
|
****
|
*
|
***
|
|
Bertin 2011 [34]
|
Retrospective
|
Cohort
|
22
|
***
|
*
|
***
|
|
Saleem 2010 [46]
|
Retrospective
|
Cohort
|
15
|
***
|
*
|
**
|
|
BE-ERCP
|
|
Kashani 2018 [51]
|
Retrospective
|
Cohort
|
103
|
***
|
*
|
***
|
|
Bukhari 2018 [33]
|
Retrospective
|
Case-control
|
30
|
***
|
**
|
***
|
|
Kumar 2016 [42]
|
Retrospective
|
Case-control
|
12
|
***
|
**
|
***
|
|
Choi 2013 [50]
|
Retrospective
|
Case-control
|
28
|
***
|
*
|
**
|
|
Schreiner 2012 [47]
|
Retrospective
|
Case-control
|
32
|
****
|
**
|
***
|
|
EDGE
|
|
Wang-2019 [17]
|
Prospective
|
Cohort
|
9
|
***
|
*
|
***
|
|
Chiang 2018 [15]
|
Retrospective
|
Cohort
|
66
|
***
|
*
|
*
|
|
James 2018 [16]
|
Retrospective
|
Cohort
|
19
|
***
|
*
|
***
|
|
Bukhari 2018 [33]
|
Retrospective
|
Case control
|
30
|
***
|
**
|
***
|
LA-ERCP, laparoscopic endoscopic retrograde cholangiopancreatography; BE-ERCP, balloon
endoscopic retrograde cholangiopancreatography; EDGE, endoscopic ultrasound-directed
transgastric retrograde cholangiopancreatography
Meta-analysis outcomes
A total of 1268 patients were included in the analysis. One hundred twenty-four patients
from four studies underwent EDGE, 939 patients from 18 studies underwent LA-ERCP,
and 205 patients from five studies underwent BE-ERCP.
Primary outcomes
-
Technical success
The calculated pooled rate of technical success ([Table 4]) with EDGE was 95.5 % (95 % CI 84.2–98.8, 95 % PI 52 to 99.7, I2 = 0), with LA-ERCP
was 95.3 % (95 % CI 91.3–97.5, 95 % PI 75.7 to 99, I2 = 46.3), and with BE-ERCP was
71.4 % (95 % CI 51–85.7, 95 % PI 6.3 to 98.9, I2 = 87). Statistical p-value was significant
for EDGE vs BE-ERCP, P = 0.01 and LA-ERCP vs BE-ERCP, P = 0.001 but was not significant for EDGE vs LA-ERCP, P = 0.98.
-
Clinical success
The calculated pooled rate of clinical success ([Table 4]) with EDGE was 95.9 % (95 % CI 81.2–99.2, 95 % PI 37.5 to 99, I2 = 0), with LA-ERCP
was 92.9 % (95 % CI 83.9–97.1, 95 % PI 14 to 99, I2 = 84.2), and with BE-ERCP was
58.7 % (95 % CI 27.6–84.1, 95 % PI 7.4 to 96, I2 = 0). Statistical p-value for the
difference was significant for EDGE vs BE-ERCP, P = 0.001 and La-ERCP vs be-ERCP, P = 0.009. but was not significant for EDGE vs LA-ERCP, P = 0.65.
Table 4
Pooled rates of technical success, clinical success and adverse events of EDGE, LA-ERCP
and BE-ERCP.
|
(95 % CI, I2 %, P value in comparison to EDGE)
|
EDGE
|
LA-ERCP
|
BE-ERCP
|
|
Technical success
|
95.5 % (84.2 – 98.8, 0)
|
95.3 % (91.3 – 97.5, 46.3, P = 0.98)
|
71.4 % (51 – 85.7, 87, P = 0.01)
|
|
Clinical success
|
95.9 % (81.2 – 99.2, 0)
|
92.9 % (83.9 – 97.1, 84.2, P = 0.65)
|
58.7 % (27.6 – 84.1, 0, P = 0.001)
|
|
All adverse events
|
21.9 % (14.6 – 31.4, 21.2)
|
17.4 % (14 – 21.5, 18.1, P = 0.32)
|
8.4 % (5 – 13.6, 0, P = 0.001)
|
|
PEP
|
2.2 % (0.6 – 7.4, 0)
|
6.8 % (5.3 – 8.8, 0, P = 0.07)
|
6.3 % (3.7 – 10.4, 0, P = 0.12)
|
|
Bleeding
|
6.6 % (3.3 – 13, 0)
|
3.7 % (2.6 – 5.4, 5.8, P = 0.15)
|
1.5 % (0.4 – 5, 0, P = 0.04)
|
|
Perforation
|
2.2 % (0.6 – 7.4, 0)
|
2.2 % (1.3 – 3.7, 0, P = 0.99)
|
1.8 % (0.7 – 4.7, 0, P = 0.79)
|
|
Stent migration
|
13.3 % (5.7 – 28.1, 57.6)
|
NP
|
NP
|
|
Infection
|
NP
|
5.8 % (4.4 – 7.6, 0)
|
1.9 % (0.7 – 5.2, 0, P = 0.04 as compared to la-ERCP)
|
LA-ERCP, laparoscopic endoscopic retrograde cholangiopancreatography; BE-ERCP, balloon
endoscopic retrograde cholangiopancreatography; EDGE, endoscopic ultrasound-directed
transgastric retrograde cholangiopancreatography; PEP, post-ERCP pancreatitis; NP,
not provided
Secondary outcomes
The pooled rates of all AEs and AE subtypes with EDGE, LA-ERCP, and BE-ERCP are summarized
in [Table 2] (Forest plots: Supplementary Fig. 2, 3, 4, 5, 6, 7, 8, 9). Pooled rates of PEP and perforation were comparable between the groups, whereas
the pooled rate of bleeding with BE-ERCP was 1.5 % (95 % CI 0.4–5, I2 = 0), which
was significantly lower when compared to EDGE and LA-ERCP, P = 0.04.
Validation of meta-analysis results
Sensitivity analysis
To assess whether any one study had a dominant effect on the meta-analysis, we excluded
one study at a time and analyzed its effect on the main summary estimate. On this
analysis, no single study significantly affected the outcome or the heterogeneity.
Therefore, including or excluding either one of the studies by Chiang et al [15] and/or Bukhari et al [35] would give us essentially the same pooled results.
Heterogeneity
We assessed dispersion of the calculated rates using the prediction interval (PI)
and I2 percentage values. The PI gives an idea of the range of the dispersion and
I2 tell us what proportion of the dispersion is true vs chance [54]. The pooled rate of technical success with LA-ERCP had a narrow PI, whereas EDGE
and be-ERCP had wide PI with heterogeneity. The PI for clinical success was wide with
all the modalities, suggesting heterogeneity.
Publication bias
Based on visual inspection of the funnel plot (Supplementary Fig. 10), there seemed to be possible publication bias, but quantitative measurement that
used the Egger regression test, the statistical 2-tailied P value was not significant for publication bias (P = 0.15).
Discussion
Our study demonstrated that, in patients with RYGB, EDGE procedure has comparable
technical and clinical success rates to LA-ERCP and has a statistically superior technical
and clinical success rates when compared to BE-ERCP. To our knowledge, this is the
first meta-analysis comparing the outcomes of EDGE, LA-ERCP, and BE-ERCP in patients
with RYGB.
Based on our analysis, the pooled rate of technical success of EDGE in RYGB patients
was comparable to LA-ERCP (96.5 vs 95%, P = 0.98) but was statistically superior to BE-ERCP (96 % vs 71 %, P = 0.01). Similarly, the pooled clinical success rate with EDGE was comparable to
LA-ERCP (96 % vs 93 %, P = 0.65) and markedly superior to BE-ERCP (96 % vs 59 %, P = 0.001).
The core reason for the technical success of EDGE is the advent and commercial availability
of LAMS which creates a tract for passage of the endoscope (easily bringing the papilla
within reach).
Clinical success of EDGE in most the studies was also 100 % [16]
[17]
[35] except for one study where it was 92 % [15]. The clinical success of the procedure was directly related to the technical success
of the procedure, indicating the importance of a successful transluminal access procedure
and operator expertise.
All AEs and subtypes of AEs (PEP, bleeding, perforation) were comparable between EDGE
and LA-ERCP. However, when compared to BE-ERCP, EDGE had higher incidence of AEs.
It is, however, interesting to note that rates of PEP were comparable between all
the three groups. The absolute rate of PEP was the lowest with EDGE procedure and
showed a trend towards statistical significance when compared to LA-ERCP.
LAMS migration was the most common AE encountered with a pooled event rate of 13.3 %.
The main causes of stent migration are immaturity of the fistula and the manipulation
of the LAMS via the duodenoscope resulting in LAMS dislodgement. This risk can potentially
be reduced via performing a two-stage procedure so as to allow the fistula to mature
before it is traversed. Study with a higher percentage of two-stage procedure had
a lower rate of stent migration [35]. Also, lubricating the scope generously showed decreased migration in one study
[33].
Weight gain is an AE that was a concern due to presence of a persistent fistula following
EDGE. Only one study reported weight gain in our literature search [35]. All the other studies reported an overall average weight loss [32]
[33]
[34]
[35]. The reason for weight loss is unclear, but it has been hypothesized that majority
of the food flows through the Roux tract and not through the fistula resulting in
weight loss [33].
Failure of the fistula to close is another concerning AE for EDGE. Various techniques
have been described to prevent this including exchange of LAMS with plastic stents,
endoscopic suturing and OTSC (over-the scope-clips) or a combination thereof. Limited
data is available on the mechanism of plastic stents and its role in closure of fistula.
It works likely by irritation of mucosa resulting in granulation tissue formation
resulting in closure of fistula [17]. More data are needed on this aspect to find out the best way to facilitate closure
of the fistula.
The strengths of this review are as follows: systematic literature search with well-defined
inclusion criteria, careful exclusion of redundant studies, inclusion of good quality
studies with detailed meticulous extraction of data, rigorous evaluation of study
quality, and statistics to establish and/or refute the validity of the results of
our meta-analysis. Heterogeneity was minimal to zero with the pooled outcomes of EDGE.
We report the prediction intervals for the primary outcomes, thereby enabling our
results to be applicable to the real population. With 1268 patients and 27 studies,
this is the largest, most comprehensive, and up-to-date meta-analysis evaluating and
comparing EDGE, LA-ERCP, and BE-ERCP in RYGB anatomy patients.
There were limitations to this study, most of which are inherent in any meta-analysis.
The included studies were not entirely representative of the general population and
community practice, with most studies being performed in tertiary-care referral centers.
Also, the procedure is a novel procedure and does not reflect the skill of an average
endoscopist. Our analysis had studies that were retrospective in nature contributing
to selection bias. Our analysis has the element of indirect comparison. Nevertheless,
this study is the best available in literature thus far with respect to EDGE. More
studies are warranted to better evaluate the clinical performance of EDGE procedure,
especially with respect to its adverse events.
Conclusion
In conclusion, our meta-analysis demonstrates that the technical and clinical success
of EDGE procedure is better than BE-ERCP and comparable to that of LA-ERCP in RYGB
patients. EDGE is not as expensive as LA-ERCP, minimally invasive, and can be performed
by one endoscopist in one session if needed, although it is usually performed in a
two-stage manner. EDGE also has a similar safety profile as compared to LA-ERCP but
has higher adverse event rate as compared to BE-ERCP.
