Introduction
Malignant disease accounts for an estimated 50 % to 80 % of cases of gastric outlet
obstruction (GOO), with pancreatic cancer being the most common associated malignancy
(15 %–20 %) [1 ]. Patients with GOO may experience progressively worsening nausea, vomiting, weight
loss, abdominal pain and severe dehydration [2 ]. Because patients with GOO secondary to an unresectable malignancy have limited
life expectancy, palliative treatment prioritizes symptom resolution (especially relief
of vomiting and return to oral intake) and minimization of hospital stays, complications
and reinterventions [1 ].
Palliative interventions for GOO include open or laparoscopic surgical gastrojejunostomy
(GJ), duodenal stenting using self-expanding metal stents (SEMS), and endoscopic gastroenterostomy
(EUS-GE). Surgical GJ and SEMS are the two most common palliative treatment options
for patients with malignant GOO [2 ]. A 2019 meta-analysis of data from 27 studies including 2354 patients with malignant
GOO found similar technical and clinical success rates for surgical GJ and duodenal
stenting, with shorter mean time to resumption of oral intake for patients who received
stenting [2 ]. However, because stenting was associated with shorter survival time (mean difference
43 days) and higher rates of stent‑related complications, reobstruction and reintervention
compared to surgical GJ, the authors concluded that surgical GJ was preferable for
patients with a long life expectancy and good performance status [2 ]. A 2018 meta-analysis of the same treatments analyzed only three randomized controlled
trials (RCTs) including 84 patients after exclusion of many studies for low-quality
data [1 ]. This analysis confirmed that compared to surgical GJ, patients receiving duodenal
stenting had a faster return to oral intake, shorter mean hospital stay, increased
recurrence of symptoms and increased reintervention rate, while quality of life and
survival could not be analyzed due to insufficient adequate-quality data [1 ].
Since 2015 [3 ], endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has been studied for the
management of GOO. A meta-analysis of 12 studies published through 2018 including
285 patients concluded that EUS-GE is effective and safe for patients with malignant
GOO, estimating 92 % technical success, clinical success in 90 % of patients, symptom
recurrence or unplanned reintervention in 9 % and adverse events (AEs) in 12 % [4 ]. Subsequently, a 2020 multicenter study of 45 patients showed lower technical (86.7 %)
and clinical (73.3 %) success rates with AEs in 12 patients (26.7 %), including five
fatal AEs that occurred at one center [5 ].
The above treatments have been studied in observational studies and 2-arm randomized
trials. No clinical trials have included all three treatments in a head-to-head comparison.
To address this evidence gap, we conducted a systematic review and meta-analysis comparing
the efficacy and safety of duodenal SEMS versus EUS-GJ versus surgical GJ in observational
studies.
Methods
Search strategy
An expert librarian conducted searches of the Embase and MEDLINE databases (via Embase.com)
to identify studies published in English between January 2015 and February 2021 (eTable 1 ). January 2015 was chosen as the search start date because EUS-GE (newest of the
three treatments) was first documented for the management of GOO in human patients
in 2015 [3 ]. RCTs, retrospective and prospective cohort studies, case-control studies, and case
series that assessed endoscopic duodenal stenting or endoscopic or surgical GJ for
malignant GOO were included. We excluded in vitro or animal studies, reviews or editorials,
and publications that reported on < 10 patients, had article text in a non-English
language, or had study populations that were clearly overlapping or had suspected
overlap based on common authors and study sites with overlapping enrollment dates.
In cases of overlap, we retained the study/studies with the most comprehensive data
on the outcomes of interest that were mutually exclusive with all other included studies.
If some but not all arms of a comparative study showed overlap with another publication,
the arm(s) with overlap were excluded but the arm(s) without overlap were retained
for the analysis.
Data extraction and assessment for risk of bias
For all manuscripts identified by the literature search, two authors (RK, SB) independently
reviewed studies for eligibility and/or extracted data from selected publications
for preidentified efficacy and safety endpoints. Discrepancies were resolved after
review by a third author (PB) and consensus decision after discussion among the entire
author group. Baseline information consisted of study characteristics (year published,
country of origin, study design, sample size), patient characteristics (age, sex),
treatment and treatment subgroup (e. g., type of stent, subcategory of surgery). Reasons
for study exclusion were documented.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines
were used to conduct this analysis [6 ]. The Newcastle-Ottawa Scale (NOS) was employed (author SB) to review the methodologic
quality of non-randomized studies and assess for bias. An adapted NOS was used that
assessed the selection and representativeness of the study population (eTable 2 ) and the ascertainment of outcomes and exposures. Items from the NOS that made comparative
assessments (e. g. exposed vs. non-exposed cohorts) were removed, as they did not
apply to single-arm studies. This adaptation of the NOS has been used previously [7 ]
[8 ]
[9 ], and for the purposes of this study, one question (“Were other important diagnoses
excluded?”) was replaced by another question (“Was follow-up long enough for outcomes
to occur? Reported adequate follow-up time”) to make it more appropriate for this
systematic review. Yes/no responses were required for each of five questions, and
the quality of each study was ranked as good (5 yes responses), moderate (4 yes responses),
or poor ( ≤ 3 yes responses).
Endpoint assessment and definition
Efficacy outcomes assessed were “technical success” and “clinical success” as defined
by the reporting authors, pre- and postprocedural Gastric Outlet Obstruction Scoring
System (GOOSS) score [10 ] (no oral intake = 0, liquids only = 1, soft solids = 2, low-residue or full diet = 3),
recurrence of GOO, and reintervention (for any reason) during the study period.
Safety outcomes assessed were overall adverse event rate, procedure-related bleeding
and perforation, and for the duodenal stent and EUS-GE arms: stent migration, patency,
occlusion, ingrowth and overgrowth. In many cases, procedure-related deaths were not
distinguished from all-cause deaths, and some studies were designed to follow all
patients until death. Therefore, as a surrogate of procedure-related deaths, we only
extracted deaths described in the AEs section since this location in the paper suggested
the authors thought the death could be procedure-related.
In some articles, some outcomes were only reported for technically successful cases.
To avoid inflated estimates (e. g. clinical success only reported for technically
successful cases) or exclusion of AEs in failed cases, all reported events were extracted,
using denominators reflecting the entire study population.
Statistical methods
Efficacy and safety outcomes were assessed using a random-effects meta-analysis to
estimate the proportion of patients with the measure or mean of the measure. Since
the number of comparative studies was small and those studies were retrospective,
both arms from all comparative studies were treated as independent studies and combined
with non-comparative studies. The arcsine transformation was used to compute weighted
pooled random-effects estimates for all endpoints. For endpoints with three treatment
groups, pairwise comparisons between treatments were done with a Bonferroni adjustment.
A sensitivity analysis was performed including only studies with “good” quality ratings.
Heterogeneity was assessed across studies using the I2 statistic [11 ]. Funnel plots were created to assess for publication bias across studies. The Begg
and Mazumdar rank correlation test of funnel plot asymmetry and Egger’s linear regression
test of funnel plot asymmetry were also used to assess publication bias [12 ]
[13 ]. All meta-analyses were performed using R (version 3.6.1); SAS (version 9.4, SAS
Inc., Cary, North Carolina, United States) was used for plotting and all other analyses.
Results
Study selection and patient characteristics
Study and patient characteristics are summarized in [Table 1 ]. The systematic literature search identified 451 unique articles, of which 61 studies
representing 5772 subjects met the inclusion criteria ([Fig. 1 ]). In total, 390 articles were excluded ([Fig. 1 ]), most often for the wrong indication (including benign GOO) or being unrelated
to the search objectives (n = 211), or because they were a review article or editorial
(n = 65), case report or had < 10 patients (36), in vitro or animal study (32) or
not available in English language (31). Fifty-two eligible studies were retrospective;
and nine were prospective, including two randomized studies comparing covered SEMS
to uncovered SEMS.
Table 1
Publications and extracted data.
First author
Year
Country
Study design
Treatment
Treatment subgroup
No. of Cases
Age [mean± SD]
Males (x/n)
Chiu [32 ]
2015
UK
Retrospective
SEMS
Uncovered
18
70 median (range 46–85)
8/18
JW Kim [33 ]
2015
South Korea
Retrospective
SEMS
Uncovered
38
68.9 ± 10.2
18/38
SEMS
Covered
29
68.5 ± 11.2
11/29
SH Kim [34 ]
2015
South Korea
Retrospective
SEMS
27 Covered stents, 29 uncovered
56
69 mean (range 52–91)
36/56
H Lee [35 ]
2015
South Korea
Prospective randomized; WAVE partially covered SEMS vs uncovered SEMS
SEMS
Partially covered
51
57.9 ± 12.5
34/51
SEMS
Uncovered
51
58.7 ± 10.8
36/51
JE Lee [23 ]
2015
South Korea
Retrospective
SEMS
60 Uncovered, 7 partially covered
67
61.2 ± 12.7
41/67
SEMS
80 Uncovered; eight partially covered
88
64.4 ± 12.8
61/88
D Oh [36 ]
2015
South Korea
Retrospective
SEMS
Partially covered
20
64.5 median (range 39–85)
11/20
SY Oh [37 ]
2015
USA
Retrospective
SEMS
NS
196
65.4 median (IQR 59.4–74.2)
102/196
SEMS
NS
96
70.4 median (IQR 61.0–79.2)
55/96
Park [24 ]
2015
South Korea
Retrospective
SEMS
Mixed (141 uncovered, 76 covered)
217
60.7 ± 13.3
162/217
Surgical
Mixed
39
61.7 ± 13.3
34/39
Sato [38 ]
2015
Japan
Retrospective
SEMS
Uncovered
61
64.0 ± 10.3
35/61
Trotter [39 ]
2015
UK
Retrospective
SEMS
NS
29
Fiori [40 ]
2016
Italy
Prospective, not randomized
SEMS (arm excluded for overlap)[1 ]
Mixed covered and uncovered[1 ]
72[1 ]
71[1 ]
46/70[1 ]
Surgical
Open
30
70
19/30
Grunwald [41 ]
2016
USA
Retrospective
SEMS
NS
100
69.7
43/100
Itoi [42 ]
2016
Japan, India, USA
Prospective
EUS-GJ (EPASS) with LAMS
EUS-GJ
20
Jung [43 ]
2016
South Korea
Retrospective
SEMS
Fully covered
SEMS
Partially covered
SEMS
Uncovered
SEMS
Mixed
220
63 median (IQR 15–90)
125/220
Kato [44 ]
2016
Japan
Retrospective
SEMS
Uncovered
46
SEMS
Uncovered
79
SEMS
Uncovered
125
70.2 mean (range 38–97)
71/125
Khan [45 ]
2016
China
Prospective
SEMS
Uncovered
30
65 mean (range 40–90)
18/30
Kobayashi [46 ]
2016
Japan
Retrospective
SEMS
Uncovered
71
67.6 (range: 31–92)
43/71
Lye [47 ]
2016
Singapore
Retrospective
SEMS
Uncovered
24
79.5 median (range 49–92)
11/24
Surgical
Open
30
Okuwaki [48 ]
2016
Japan
Retrospective
SEMS
Uncovered
14
72 median (IQR 69–79)
9/14
SEMS
Uncovered
17
71 median (IQR 66–75)
8/17
J-H Park (1) [49 ]
2016
South Korea
Retrospective
SEMS
Partially covered
125
61 mean (range 25–89)
81/125
SEMS
Partially covered
68
62 mean (range 36–91)
48/68
J-H Park (2) [50 ]
2016
South Korea
Retrospective propensity score-matched
SEMS
Dual stent consisting of outer partially covered stent and inner bare stent
74
62.1 ± 13.8
57/74
Surgical
Mixed
74
61.1 ± 12.1
55/74
Rademacher [51 ]
2016
Germany
Retrospective
SEMS
NS
62
70.5 median (range 63–81)
35/62
Sasaki [52 ]
2016
Japan
Prospective
SEMS
Uncovered
39
69.2 ± 13.3
25/39
Shin [53 ]
2016
South Korea
Retrospective
SEMS
Mixed
124
71.8 median (range 42–97)
70/122
Tsauo [54 ]
2016
South Korea
Retrospective
SEMS
Partial
75
61.7 ± 10.9
45/75
Surgical
Mixed
32
63.4 ± 9.6
21/32
Yamao [55 ]
2016
Japan
Retrospective
SEMS
Mixed covered and uncovered
278
71.7 ± 11.4
163/278
Bulut [56 ]
2017
Turkey
Retrospective
SEMS
Uncovered
53
58.7 ± 15.07
33/53
Chen [30 ]
2017
USA, Japan (EUS-GJ) USA (SEMS)
Retrospective
SEMS
NS
52
64 ± 13.2
32/52
EUS-GJ
EUS-GJ
30
70 ± 13.3
17/30
Hori [57 ]
2017
Japan
Retrospective
SEMS
Uncovered
126
74 median (range 39–101)
160/252
SEMS
Covered
126
Jang [58 ]
2017
South Korea
Retrospective
SEMS
NS
99
58.8 ± 13.2
67/99
Surgical
Mixed
45
58.9 ± 11.4
36/45
Khashab [59 ]
2017
USA, Japan
Retrospective
EUS-GJ (arm excluded for overlap)[1 ]
30[1 ]
70 ± 13.3[1 ]
17/30[1 ]
Surgical
Open
63
68 ± 9.6
32/63
Kim [60 ]
2017
South Korea
Retrospective
SEMS
Partially covered
18
71.2 ± 10.0
9/18
Ojima [61 ]
2017
Japan
Retrospective
Surgical
Open
23
67 median (range 45–85)
15/23
Surgical
Lap
30
71 median (range 52–85)
20/30
Perez-Miranda [62 ]
2017
USA, Spain, France
Retrospective
EUS-GJ[1 ]
EUS-GJ[1 ]
25[1 ]
63.9[1 ]
11/25[1 ]
Surgical
Lap, with conversion to open at surgeon's discretion
29
75.8
22/29
Takahara [63 ]
2017
Japan
Retrospective
SEMS
Partially covered
41
67 median (range 35–89)
26/41
Tanaka [64 ]
2017
Japan
Retrospective
Surgical
lap
43
67 median (range 43–83)
29/43
Tsauo [65 ]
2017
South Korea
Retrospective
SEMS
Dual stent consisting of outer partially covered stent and inner bare stent
40
56.8 ± 10.6
23/40
Ye [66 ]
2017
Taiwan
Retrospective
SEMS
Uncovered
87
71.1 ± 14.6
58/87
Yoshida [67 ]
2017
Japan
Retrospective
SEMS
Uncovered
23
70 (range 48–87)
15/23
Surgical
Mixed (28 open, 2 lap)
30
63.5 (range 46–72)
16/30
SEMS
Uncovered
23
70 (range 48–87)
15/23
Bekheet [68 ]
2018
South Korea
Retrospective
SEMS
Covered
55
60.6 (range 38–89)
35/55
Choi [69 ]
2018
South Korea
Retrospective
SEMS (Bonastent Wing)
Partially covered
63
65.0 (range 58.5–75.0)
44/63
Leiyuan [70 ]
2018
China
Retrospective
SEMS
NS
29
64.6 ± 14.2
19/29
Surgical
Lap
34
59.8 ± 15.5
21/34
Uemura [71 ]
2018
Japan
Retrospective
SEMS
Uncovered
64
72 (range 43–90)
32/64
Surgical
Open
35
68 (range 47–87)
12/35
Yukimoto [72 ]
2018
Japan
Retrospective
SEMS
Uncovered
38
73.0 median (IQR 65.0–79.0)
23/38
Surgical
Open
27
75.0 median (IQR 66.0–81.5)
18/27
Ge [22 ]
2019
USA
Prospective
SEMS
Uncovered
78
65.7 ± 12.6
47/78
EUS-GJ
EUS-GJ
22
66.4 ± 9.2
9/22
Jang [73 ]
2019
USA
Retrospective
SEMS
Uncovered
183
66.2 ± 14.3
90/183
Surgical
Mixed
127
67.5 ± 11.1
80/127
Kerdsirichairat [74 ]
2019
USA
Retrospective
EUS-GJ
malignant
48
65 median for all
28/57 for all
EUS-GJ[1 ]
Benign[1 ]
9[1 ]
Kumar [75 ]
2019
India
Retrospective
SEMS
NS
90
56.4 ± 11.7
43/90
SEMS
NS
24
56.9 ± 11.6
12/24
Ramos [76 ]
2019
Brazil
Retrospective
Surgical
Gastric partitioning
30
67.5 ± 13.4
22/30
Surgical
Conventional GJ
30
64.3 ± 12.7
19/30
Ratone [77 ]
2019
France
Retrospective
SEMS
Uncovered
220
67.2 ± 13.9
123/220
Sterpetti [78 ]
2019
Italy
Prospective
SEMS
87
71
57/87
Alcala-Gonzalez [79 ]
2020
Spain
Retrospective
SEMS
Uncovered
36
68 median (IQR 53–83)
20/36
Kastelijn [5 ]
2020
The Netherlands, Germany, Spain, Italy
Retrospective
EUS-GJ
EUS-GJ
45
69.9 ± 12.3
22/45
Miwa [80 ]
2020
Japan
Prospective
SEMS
Uncovered
31
70 median (range 52–90)
19/31
Mo [81 ]
2020
South Korea
Retrospective
SEMS
61 Uncovered, 29 covered initially
90
72.1 (range 31–96)
59/90
Wu [82 ]
2020
Taiwan
Retrospective
SEMS
Uncovered
71
63 ± 16
36/71
SEMS
Uncovered
32
62 ± 12
17/30
Xu [83 ]
2020
China
Retrospective
EUS-GJ
EUS-GE
36
69.0 ± 12.8
17/36
Yildirim [84 ]
2020
Turkey
Retrospective
Surgical
Open
37
68.7 ± 14.4
25/37
Surgical
Mixed (2 lap, 14 open)
16
62.7 ± 10.2
11/16
Hindryckx [85 ]
2021
Belgium
Retrospective
EUS-GJ
EUS-GJ
6
Kouanda [86 ]
2021
USA
Retrospective
EUS-GJ
EUS-GJ
36
70.4 ± 11.8
20/36
Surgical
Open
14
71.5 ± 15.6
8/14
Yamao [87 ]
2021
Japan
Prospective randomized
SEMS
Covered
182
73.5 median (range 35–97)
98/182
SEMS
Uncovered
184
72 median (range 43–96)
107/184
SEMS, self-expanding metal stent; EUS-GJ, endoscopic ultrasound-guided gastrojejunostomy.
1 Trial arms were excluded due to overlap with one or more other studies.
Fig. 1 Flow diagram of literature search and study selection.
Patients who were treated with EUS-GJ were significantly older than patients who were
treated with duodenal SEMS or surgical GJ (mean age 69.1 for EUS-GJ, 64.2 for duodenal
SEMS, 64.3 years for surgical GJ, P = 0.0004) The EUS-GJ treatment group had a lower proportion of males than the surgical
GJ group (50.3 % vs. 65.6 %, P = 0.0042 for pairwise comparison). The preprocedural GOOSS scores were similar among
groups (0.62 for duodenal SEMS vs. 0.60 for EUS-GJ vs. 0.68 for surgical GJ, P = 0.7783).
Study quality
All 61 publications were assessed for quality with the modified NOS. Thirty-eight
studies were judged to have good quality, 17 moderate quality, and six poor quality
(eTable 2 ).
Assessment of heterogeneity
Heterogeneity was found in the analyses endpoints (eTable 3 ). There was heterogeneity in the EUS-GE and SEMS groups for technical success, stent
migration, and death reported in AE section, in the Surgical GJ and SEMS groups for
clinical success, reintervention, procedure-related complications, and pre- and postprocedural
GOOSS score, and for the SEMS group only for bleeding, recurrence of GOO, stent occlusion,
ingrowth, and overgrowth. No heterogeneity was found in the analyses of perforation
and patency for any group.
Efficacy outcomes
Technical success
Forty-four of 61 (72.1 %) studies reported rates of procedural technical success.
Consistent with its more recent development, EUS-GE was reported to have a significantly
lower rate of technical success than the other two treatments (pooled rates 95.3 %
for EUS-GE vs. 99.4 % for duodenal SEMS [P = 0.0495 for pairwise comparison] and 95.3 % for EUS-GE vs. 99.9 % for surgical GJ
[P = 0.0060 for pairwise comparison]) ([Table 2 ]).
Table 2
Summary of efficacy and safety meta-analytic outcomes for three treatments for malignant
gastric outlet obstruction.
Duodenal SEMS
EUS-GJ
Surgical GJ
P value[1 ]
N studies
N patients
% (95 % CI)
N studies
N patients
% (95 % CI)
N studies
N patients
% (95 % CI)
Efficacy outcomes
45
4413
99.4 % (98.9 % to 99.8 %)
8
245
95.3 % (89.3 % to 98.9 %)
13
564
99.9 % (99.5 % to 100.0 %)
0.0048
45
4590
88.9 % (86.7 % to 90.9 %)
8
245
89.0 % (82.3 % to 94.3 %)
13
588
92.3 % (86.9 % to 96.3 %)
0.49
27
2655
0.62 (0.50 to 0.73)
2
65
0.60 (0.44 to 0.76)
6
215
0.68 (0.52 to 0.83)
0.78
19
2184
2.27 (2.12 to 2.41)
2
59
2.57 (1.83 to 3.32)
5
180
2.20 (1.48 to 2.92)
0.71
11
573
28.7 % (19.7 % to 38.6 %)
1
25
4.0 % (0.0 % to 15.0 %)
8
342
16.9 % (11.6 % to 23.0 %)
0.0036
33
2963
20.3 % (16.9 % to 23.9 %)
4
129
11.2 % (4.9 % to 19.6 %)
9
418
12.6 % (6.6 % to 20.1 %)
0.041
Safety outcomes
43
4285
18.7 % (14.7 % to 23.1 %)
6
189
21.9 % (16.3 % to 28.1 %)
16
746
23.8 % (18.6 % to 29.5 %)
0.32
25
2854
1.7 % (0.9 % to 2.7 %)
4
141
2.9 % (0.2 % to 8.6 %)
9
412
5.2 % (3.2 % to 7.5 %)
0.0048
24
2823
1.6 % (1.1 % to 2.3 %)
3
105
2.8 % (0.0 % to 10.7 %)
3
170
2.0 % (0.0 % to 7.3 %)
0.88
33
3451
4.8 % (3.6 % to 6.1 %)
4
116
2.4 % (0.0 % to 10.1 %)
0
---
---
0.45
22
1993
12.9 % (7.9 % to 18.8 %)
3
69
0.5 % (0.0 % to 4.2 %)
0
---
---
0.0002
22
2172
10.9 % (7.5 % to 14.8 %)
1
24
4.2 % (0.0 % to 15.6 %)
0
---
---
0.22
3
140
85.9 % (79.7 % to 91.2 %)
0
---
---
0
---
---
---
20
1962
5.5 % (4.1 % to 7.1 %)
0
---
---
0
---
---
---
0
---
---
0
---
---
5
196
16.1 % (6.8 % to 28.2 %)
---
26
2151
0.8 % (0.2 % to 1.7 %)
4
151
1.7 % (0.0 % to 8.7 %)
8
421
0.9 % (0.1 % to 2.9 %)
0.89
47
4711
---
8
243
---
18
818
---
SEMS, self-expanding metal stent; EUS-GJ, endoscopic ultrasound-guided gastrojejunostomy;
GOO, gastric outlet obstruction; GOOSS, Gastric Outlet Obstruction Scoring System;
AE, adverse event.
1
P value for comparison of duodenal SEMS vs. EUS-GJ vs. surgical GJ.
Clinical success
Five distinct definitions of “clinical success” were documented among 51 of 61 (83.6 %)
studies that reported this endpoint. The most common definition was improved clinical
symptoms (especially obstructive symptoms and vomiting) and/or improved oral intake
or GOOSS score (19 studies), followed by change in GOOSS score (18), followed by improved
oral intake (12), improved oral intake and hospital discharge (1), and resolution
of GOO symptoms (intractable vomiting necessitating gastric drainage) the day after
stent implantation (1). Pooled rates of “clinical success” were similar among the
three treatments, with 88.9 % for duodenal SEMS, 89.0 % for EUS-GE, and 92.3 % for
surgical GJ (P = 0.49) ([Fig. 2a ], [Table 2 ]). Among studies reporting outcomes for laparoscopic GJ alone, open surgical GJ alone,
or mixed laparoscopic or surgical GJ, rates of clinical success were similar (96.6 %
vs. 85.9 % vs. 93.8 % respectively, P = 0.2903).
Fig. 2a Analysis of efficacy outcomes. Outcomes for clinical success.
Fig. 2a Analysis of efficacy outcomes. Outcomes for clinical success.
Fig. 2b Analysis of efficacy outcomes. Outcomes for preprocedural GOOSS score.
Fig. 2c Analysis of efficacy outcomes. Outcomes for postprocedural GOOSS score.
Fig. 2d Analysis of efficacy outcomes. Outcomes for recurrence of GOO.
Fig. 2e Analysis of efficacy outcomes. Outcomes for reintervention.
Pre-procedure and post-procedure GOOSS score
Pooled estimates of mean preprocedural GOOSS score 0.62 for duodenal SEMS, 0.60 for
EUS-GE, and 0.68 for surgical GJ, reflecting minimal oral intake before treatment
([Fig. 2b ], [Table 2 ]). Estimated mean postprocedural GOOSS scores exceeded two for all three treatments
(2.27 for duodenal SEMS, 2.57 for EUS-GE, and 2.20 for surgical GJ), suggesting that
most patients were able to eat solid food after treatment ([Fig. 2c ], [Table 2 ]).
Recurrence of GOO
Recurrence of GOO in the EUS-GE group (4.0 %, 95 % CI 0.0 % to 15.0 %) was significantly
lower than for duodenal SEMS (28.7 %, 95 % CI 19.7 % to 38.6 %; P = 0.0040 for pairwise comparison) and similar to surgical GJ (16.9 %, 95 % CI 11.6 %
to 23.0 %; P = 0.11 for pairwise comparison) ([Fig. 2d ], [Table 2 ]). Only one EUS-GE study (N = 25 patients) was included in this comparison, while
11 studies of duodenal SEMS (573 patients) and eight studies of surgical GJ (342 patients)
were represented.
Reintervention
Rates of reintervention (for any reason) during the study period were lower for EUS-GE
(11.2 % among 129 patients in four studies) and surgical GJ (12.6 % among 418 patients
in nine studies) than for duodenal SEMS (20.3 % among 2963 patients in 33 studies)
(P = 0.041 for comparison of all three treatments, pairwise comparisons did not show
significant differences) ([Fig. 2e ], [Table 2 ]).
Safety outcomes
Any procedure-related serious adverse event
The pooled rate of any procedure-related serious adverse event was similar among the
three treatments, i. e. 18.7 %, 95 % CI 14.7 % to 23.1 % for SEMS vs. 21.9 %, 95 %
CI 16.3 % to 28.1 % for EUS-GE vs. 23.8 %, 95 % CI 18.6 % to 29.5 % for surgical GJ
(P = 0.32) ([Fig. 3a ], [Table 2 ]). Among studies reporting outcomes for laparoscopic GJ alone, open surgical GJ alone,
or mixed laparoscopic or open surgical GJ, rates of procedure-related complications
were similar (17.6 % vs. 26.9 % vs. 19.3 % respectively, P = 0.1340).
Fig. 3a Analysis of safety outcomes. Outcomes for any procedure-related adverse event.
Fig. 3a Analysis of safety outcomes. Outcomes for any procedure-related adverse event.
Fig. 3b Analysis of safety outcomes. Outcomes for bleeding.
Fig. 3c Analysis of safety outcomes. Outcomes for perforation.
Fig. 3d Analysis of safety outcomes. Outcomes for stent migration.
Fig. 3e Analysis of safety outcomes. Outcomes for e tissue ingrowth.
Fig. 3f Analysis of safety outcomes. Outcomes for stent occlusion.
Fig. 3g Analysis of safety outcomes. Outcomes for stent patency.
Fig. 3h Analysis of safety outcomes. Outcomes for tissue overgrowth.
Fig. 3i Analysis of safety outcomes. Outcomes for deaths reported in AE section.
Bleeding
The bleeding rate associated with duodenal SEMS (1.7 %, 95 % CI 0.9 % to 2.7 %) was
similar to the rate for EUS-GE (2.9 %, 95 % CI 0.2 % to 8.6 %; P = 0.999 for pairwise comparison) and lower than the rate for surgical GJ (5.2 %,
95 % CI 3.2 % to 7.5 %; P = 0.0033 for pairwise comparison) ([Fig. 3b ], [Table 2 ]).
Perforation
Perforation rates were similar among the three treatments, with 1.6 % for duodenal
SEMS, 2.8 % for EUS-GE, and 2.0 % for surgical GJ (P = 0.88) ([Fig. 3c ], [Table 2 ]).
Stent-related outcomes
Duodenal SEMS and EUS-GE were reported to have similar rates of stent migration (4.8 %
vs. 2.4 % respectively, P = 0.45) ([Fig. 3d ], [Table 2 ]) and tissue ingrowth (10.9 % vs. 4.2 % [based on one study of EUS-GE], P = 0.22) ([Fig. 3e ], [Table 2 ]), while stent occlusion was significantly higher for duodenal SEMS (12.9 % vs. 0.5 %
respectively, P = 0.0002) ([Fig. 3f ], [Table 2 ]).
Stent patency (85.9 %) ([Fig. 3g ], [Table 2 ]) and tissue overgrowth (5.5 %) ([Fig. 3h ], [Table 2 ]) were adequately reported for duodenal SEMS but not for EUS-GE.
Deaths reported in adverse events section
Using deaths reported in the AEs section of the articles as a surrogate of procedure-related
deaths, all three interventions were associated with a similar risk (EUS-GE [1.7 %],
vs. duodenal SEMS [0.8 %], and surgical GJ [0.9 %] [P = 0.89]) ([Fig. 3i ], [Table 2 ]).
Sensitivity analysis
In a sensitivity analysis including 43 studies (33 SEMS, 6 EUS-GE, four surgical GJ)
rated as good quality, statistically significant differences from the main analysis
included: no significant difference in technical success (99.4 % vs. 95.2 % vs. 99.6 %,
P = 0.097) and reintervention (18.9 % vs. 11.2 % vs. 23.4 %, P = 0.082), and a significant difference in preprocedural GOOSS score (0.59 vs. 0.60
vs. 1.07, P = 0.037) among the SEMS, EUS-GJ and surgical GJ arms respectively.
Publication bias
Publication bias was suggested by a significant Begg and Mazumdar test (p ≤ 0.10)
with continuity correction for technical success in duodenal SEMS and surgical GJ,
procedure-related complications for EUS-GE and surgical GJ, and overgrowth for duodenal
SEMS (eTable 4 ). The Egger test showed a lack of symmetry of the funnel plots (eFigures 1A–1M ) for technical success (surgical GJ), reintervention (surgical GJ), procedure-related
complications (EUS-GE and surgical GJ), bleeding (duodenal SEMS), perforation (EUS-GE),
migration (EUS-GJ), overgrowth (duodenal SEMS), and preprocedural and postprocedural
GOOSS score (duodenal SEMS for both measures).
Discussion
In this systematic review and meta-analysis of 61 studies including 5772 patients
with malignant GOO, duodenal SEMS, EUS-GE and surgical GJ were found to achieve similar
rates of clinical success and similar improvement in dietary intake. EUS-GE was reported
to have the lowest rate of technical success and (based on one study) lowest recurrence
of GOO, while duodenal SEMS had the highest rate of reintervention. Overall procedure-related
AEs were similar among the treatments, but duodenal SEMS had a lower bleeding rate
than the other two treatments and a higher rate of stent occlusion than EUS-GE.
Surgical GJ for GOO evolved from an open procedure performed for a patient with a
duodenal ulcer in 1884 [14 ], to the introduction of laparoscopic GJ in 1992 [15 ]. Laparoscopic GJ has shown improved morbidity and mortality rates compared with
the open surgical approach [16 ], for which delayed gastric emptying rates of 20 % or more and overall complication
rates of 25 % to 35 % have been reported [1 ]. Endoscopic duodenal stenting using SEMS was described in the early 1990 s as a
minimally invasive treatment for malignant GOO [17 ]. While periprocedural outcomes for duodenal stenting are favorable, high reocclusion
rates increase the risk of obstruction and need for reintervention over time [18 ]. A 2020 multicenter prospective study of EUS-GE reported a high rate of AEs including
five fatalities [5 ]. However, because the deaths were reported at one center, these results might be
more reflective of an early phase of procedural training than of long-term expected
outcomes at centers with endoscopists who are familiar with the technique [19 ].
Our findings are consistent with the 2021 American Gastroenterology Association Clinical
Practice Update on the Optimal Management of the Malignant Alimentary Tract Obstruction
[20 ]. This expert review advised that for surgical candidates with GOO having life expectancy
greater than 2 months and good functional status, surgical GJ should be considered,
preferably using a laparoscopic approach [20 ]. EUS-GE was considered an acceptable alternative to surgical GJ depending on the
endoscopist’s experience, while patients who are not candidates for surgical or endoscopic
GE should be considered for an enteral stent [20 ]. Similarly, the European Society of Gastrointestinal Endoscopy (ESGE) currently
recommends EUS-GE performed in an expert setting for malignant GOO, as an alternative
to enteral stenting or surgery [21 ]. EUS-GE is a newer procedure requiring advanced endoscopist expertise; therefore
should currently be limited to specialized endoscopy centers with high procedural
volume and endoscopists trained in this advanced therapeutic EUS approach. Our results
reflect the early stage of EUS-GE procedural development, including its significantly
lower reported rate of technical success and higher (but not significantly) rate of
deaths reported in the AEs sections of eligible articles. After wider dissemination
and increasing familiarity among endoscopists, EUS-GE could potentially be used more
frequently as a less invasive approach compared to surgery.
There are several considerations that go into selection of what treatment approach
is chosen for an individual patient with malignant GOO. Reviewing the cross-sectional
imaging (ideally a CT scan) to evaluate for proximity of the small bowel to the stomach,
and quantity of intervening ascites (which, should give pause at least with early
use of EUS-GE) [22 ]. Carcinomatosis with ascites predicts unfavorable long-term clinical outcomes in
patients undergoing SEMS placement for malignant GOO [23 ]
[24 ], and a large amount of ascites is currently considered by some to be an absolute
contraindication to EUS-GE [25 ]. Both covered and uncovered enteral SEMS have been utilized in the management of
malignant GOO, although, covered SEMS are not universally available worldwide (unavailable
in the US, while available in Asia and Europe). Compared to covered SEMS, uncovered
duodenal SEMS are generally thought to have lower risk of migration and lower risk
of impacting biliary and pancreatic drainage when it covers the papilla, but have
higher risk of reobstruction from tumor ingrowth [26 ]
[27 ]. Hence, the following factors could be considered in the choice of covered vs uncovered
SEMS: 1) anticipated life expectancy and aggressiveness of the tumor; 2) extraluminal
vs intraluminal tumors (tumor ingrowth is less of a problem in extrinsic tumors);
3) location of the tumor relative to the papilla; and 4) availability by region/country.
Life expectancy greater than 2 to 3 months should encourage the selection of an EUS-GE,
due to its lower rates of reintervention, and although not borne out in this meta-analysis,
a likely higher rate of initial clinical success as reported in some previous studies
and based on our experience [22 ]
[28 ]. For patients with combined obstruction of the bile duct and duodenum (common occurrence
in periampullary malignancies) at centers with adequate endoscopic expertise, EUS-GE
may have an advantage over endoscopic stenting because the site of intervention is
away from the tumor site [29 ]. Therefore, the problem of reocclusion of the stent as a result of tumor overgrowth
or ingrowth is unlikely compared to endoscopic enteral stenting [30 ]. In summary, when expertise is available, EUS-GE can be used in most cases for the
treatment of malignant GOO as a less invasive alternative to surgery. However, patients
with anticipated short survival, widespread metastasis, diffuse malignant infiltration
of the gastric wall, or uncontrolled ascites are better approached with SEMS. Surgery
can be reserved for patients with expected prolonged survival in whom less invasive
procedures are not feasible or have failed.
Our study has strengths and limitations. In the absence of a 3-arm RCT, this meta-analysis
compares the two most common palliative treatments for malignant GOO (duodenal stenting
using SEMS and surgical GJ), as well as the newer EUS-GE procedure. Our eligibility
criteria were relatively generous to include sufficient data to compare all three
treatments. While this allowed an informative review, the quality of some studies
included may be lower than reviews with stricter inclusion criteria [1 ]. Baseline characteristics among the three treatment arms were not equal for age
and proportion of males; however, similarity of preprocedural GOOSS scores suggested
that patients in all three treatment arms had similarly low levels of oral intake
at baseline. Our analysis focused on palliative treatment of symptoms associated with
malignant GOO, not on the treatment of associated conditions such as biliary obstruction,
which is estimated to occur in 40 % to 92 % of patients with malignant GOO [31 ]. EUS-GE can be performed using at least three different techniques including direct
EUS-GE, device-assisted EUS-GE, and EPASS double balloon-occluded gastrojejunostomy
bypass [25 ]. Outcomes for specific techniques might vary compared to findings for our combined
“EUS-GE” category. Time to postprocedure return to oral intake and resumption of chemotherapy,
and SEMS migration rates by postprocedure chemotherapy status could not be analyzed
because they were incompletely reported or not reported among studies. Because it
is a newer technique, limited data on EUS-GE were available for some estimates, e. g.
only one EUS-GE study was represented in the analysis of GOO recurrence. Although
available in some studies, data on mortality and survival rates was usually missing
or of very low quality as has been reported previously [1 ]. Therefore, our estimated mortality rates may have low generalizability. Incomplete
reporting (e. g. outcomes reported only in technically successful cases or other patient
subgroup) was also a barrier to comprehensive data on all outcomes.
Conclusions
Duodenal SEMS, EUS-GE and surgical GJ achieve similar rates of clinical success and
improved dietary intake. Safety profiles were similar except that bleeding was less
common and reintervention was more common for duodenal SEMS. Based on less data than
the other two treatments, EUS-GE appears to be a promising treatment for patients
with malignant GOO for whom surgery is contraindicated or less desirable.