Introduction
Roux-en-Y gastric bypass (RYGB) is one of the most common surgical bariatric procedures
performed worldwide [1], with estimates of more than 40,000 cases performed in the United States in 2018
alone [2]. Among available bariatric procedures, RYGB has been associated with the most significant
weight reduction and improvement in metabolic parameters, including diabetes mellitus,
hypertension and hyperlipidemia [3]
[4]
[5].
Although safe with low morbidity and mortality, RYGB can be associated with the onset
of late complications, including the undesirable effect of weight regain [6]. One of the anatomic causes of weight regain is the development of a gastro-gastric
fistula (GGF), which develops as an abnormal communication from the gastric pouch
and excluded remnant stomach or jejunum near the gastrojejunal anastomosis and occurs
in from 1.3 % to 6 % of operations [7]
[8]. Predominant symptoms associated with GGF include nausea, vomiting, recurrent or
new onset diabetes, abdominal pain, gastroesophageal reflux disease (GERD) and most
commonly, weight gain [7].
Although medical management with acid suppression may be utilized to manage some symptoms
associated with GGF, a large number of patients require endoscopic or surgical treatment
to perform GGF excision or closure [9]. There remains no standard approach to procedural GGF repair, as both endoscopic
and surgical (open vs laparoscopic) techniques have demonstrated success [9]
[10]
[11]. Endoscopic GGF treatment has been shown to be safe, with treatment-related adverse
events (AEs) reported between 0 % in a study involving eight patients followed between
8 and 46 months [12] and 2.1 % (n = 2) in a study involving 95 patients followed for 18 months [11]. However, despite low risk, durability of symptom resolution and GGF closure has
been variable following endoscopy, where 0 % of GGF > 20 mm and 32 % of GGF < 10 mm
have been shown to remain closed at an average of 395 days [11]. In contrast, although AE rates have been higher following surgical treatment (25 %),
GGF closure has been reported as durable in the majority of patients [9]. However, a direct comparison of symptom amelioration, durable weight loss and treatment-related
AEs between endoscopy and surgery has not previously been performed. The current study
aimed to compare the efficacy and safety of endoscopic closure and surgical revision
of GGF in RYGB patients.
Patients and methods
Study design
This was a retrospective matched cohort study of patients with GGF who underwent endoscopic
(ENDO) or surgical (SURG) treatment at two tertiary referral centers. Patients were
identified through a systematic patient search using a large Research Patient Data
Registry to evaluate patients who received treatment for GGF that was deemed technically
successful at the time of the intervention. Institutional Review Board approval was
obtained for retrospective review of data used in this study (approval number: 2003P-001597,
renewed approval on May 8, 2020).
ENDO patients were matched 1:1 to SURG patients based on age within 5 years, sex,
body mass index within 5 kg/m2 and percentage of weight regain from that lost after initial RYGB within 10 %. Data
on patient demographics, GGF size, procedural details, symptoms related to GGF and
treatment-related AEs were collected. Data on symptoms of onset or recurrence of diabetes,
acid reflux, abdominal pain and weight parameters were extracted. Inclusion criteria
included adult patients (> 18 years) with the diagnosis of GGF through prior imaging
(upper gastrointestinal series, computed tomography of the abdomen) or esophagogastroduodenoscopy
and having undergone GGF repair (endoscopic or surgical). Patients were excluded if
they underwent endoscopic or surgical treatment for an alternative diagnosis to GGF.
Measures
A comparison of symptom improvement between ENDO and SURG following GGF treatment
at 12 months was evaluated. Specifically, resolution of diabetes, acid reflux, abdominal
pain and weight parameters were compared. Weight measurements included weight regain
(defined as having gained > 15 % of maximum post-RYGB weight loss), total weight change
(lb) and percentage of total weight loss (%TWL) between GGF treatment and end of the
follow-up period. Additional comparisons were performed of overall treatment-related
AE rates and serious (severe) treatment-related AE rates between groups. Treatment-related
AEs were recorded per validated reporting standards. For treatment-related AEs associated
with endoscopy, the American Society for Gastrointestinal Endoscopy lexicon was referenced
[13]. This reporting system, developed in collaboration with representatives of the National
Surgical Quality Improvement Program, has been endorsed by the American College of
Surgeons as a reliable surgical AE reporting platform [14]
[15].
Statistical analysis
Standard statistical analyses were performed, including a Fisher’s exact test used
to compare symptom profiles and treatment-related AE rates (categorical variables)
and either student’s t-test or Wilcoxon Rank Sum test used for weight profile comparisons (continuous variables)
based on data normality. A kurtosis value < 1 was determined to exhibit adequate normality
for comparisons based on sample sizes. Comparisons were considered statistically significant
when P < 0.05. All statistical analyses were performed using SAS software, version 9.4 (SAS
Institute, North Carolina, United States).
Results
A total of 90 RYGB patients with GGF (45 ENDO, 45 matched SURG) were included ([Table 1]). Baseline characteristics were similar between groups. Specifically, the mean (SD)
age was 49.7 years (10.3) in the ENDO group compared to 49.2 years (10.2) in the SURG
group and both groups contained 37 (82.2%) females. The overall average GGF size was
15 ± 9 mm (14.6 ± 9.4 mm in the ENDO group and 15.9 ± 8.4 mm in the SURG group). The
average time between RYGB and GGF treatment was 8.9 ± 5.3 years (9.7 ± 5.7 years in
the ENDO group and 8.1 ± 4.8 years in the SURG group). GGF symptoms included new or
recurrent onset of diabetes in 11 (25.6 %) and 16 (36.4%), acid reflux in 34 (79.1 %)
and 33 (75 %), abdominal pain in 23 (53.5 %) and 33 (75 %) and weight regain in 37
(82.2%) and 35 (77.8 %) in the ENDO and SURG groups, respectively.
Table 1
Baseline cohort characteristics.
|
Characteristics
|
Endoscopy
(n = 45)
|
Surgery
(n = 45)
|
|
Sex (female) – n (%)
|
37 (82.2)
|
37 (82.2)
|
|
Age – mean (SD) years
|
49.7 (10.3)
|
49.2 (10.2)
|
|
Duration between RYGB and revision (years) – mean (SD)
|
9.7 (5.7)
|
8.1 (4.8)
|
|
Pre-RYGB weight (lb) – mean (SD)
|
307.4 (63.7)
|
299.7 (54.0)
|
|
Nadir weight (lb)
|
183.5 (45.4)
|
171.7 (44.7)
|
|
Weight at surgical revision (lb)
|
227.2 (55.1)
|
222.0 (56.6)
|
|
BMI at surgical revision (kg/m2)
|
36.9 (7.5)
|
36.8 (8.0)
|
|
Weight regain (% of maximal weight loss)
|
36.4 (22.6)
|
39.6 (25.5)
|
|
GGF size (mm)
|
14.6 (9.4)
|
15.9 (8.4)
|
|
Pre-revision symptoms – n (%)
|
|
|
11 (25.6 %)
|
16 (36.4 %)
|
|
|
34 (79.1 %)
|
33 (75 %)
|
|
|
23 (53.5 %)
|
33 (75 %)
|
|
|
37 (82.2 %)
|
35 (77.8 %)
|
Characteristics of Roux-en-Y gastric bypass patients who underwent endoscopic closure
or surgical revision of gastro-gastric fistula.
SD, standard deviation; RYGB, Roux-en-Y gastric bypass; GGF, gastro-gastric fistula.
Endoscopic closure methods ([Table 2]) included argon plasma coagulation (APC) with endoscopic suturing (n = 18), APC
with endoscopic plication (n = 7), endoscopic submucosal dissection (ESD) with endoscopic
suturing (n = 6), APC with endoscopic plication, clips and fibrin glue (n = 2), APC
with endoscopic plication and clips (n = 2), endoscopic suturing alone (n = 2), APC
with endoscopic plication and glue (n = 2), clips alone (n = 2), APC with ESD and
endoscopic suturing (n = 1), APC and clip (n = 1), clips and glue (n = 1) and stent
alone (n = 1). Endoscopic suturing was performed using the Apollo Overstitch device
(Apollo Endosurgery, Austin, Texas, United States) in an interrupted, running or purse
string fashion depending on fistula size and location. Endoscopic Plication was performed
using the Bard Endocinch device (Bard, Warwick, Rhode Island, United States). Surgical
revision methods included laparoscopic GGF resection (n = 31) or open resection of
GGF (n = 14).
Table 2
Endoscopic techniques used for fistula closure.
|
Method of endoscopic treatment
|
n = 45
|
|
APC, suture
|
18
|
|
APC, endoscopic plication
|
7
|
|
ESD, suture
|
6
|
|
APC, endoscopic plication, clips and fibrin glue
|
2
|
|
APC, endoscopic plication and clips
|
2
|
|
Endoscopic suturing alone
|
2
|
|
APC, endoscopic plication, glue
|
2
|
|
Clips alone
|
2
|
|
APC, ESD, suture
|
1
|
|
APC, clips
|
1
|
|
Clips, glue
|
1
|
|
Stent to cover fistula
|
1
|
APC, argon plasma coagulation; ESD, endoscopic submucosal dissection.
Endoscopic suturing was performed using the Apollo Overstitch device (Apollo Endosurgery,
Austin, Texas, United States). Endoscopic plication was performed using the Bard Endocinch
device (Bard, Warwick, Rhode Island, United States). Fibrin glue was used for glue.
At 12 months, both groups experienced similar resolution of diabetes mellitus and
improvement in GERD; however, endoscopic revision was associated with more frequent
improvement in abdominal pain ([Table 3]). Specifically, resolution of diabetes (among those in which diabetes was present)
occurred in one (9.1 %) and one (6.3 %) in the ENDO and SURG groups, respectively
(P = 1.0) and reflux symptoms (among those in which they were present) were improved
in seven (20.6 %) and two (6.1 %) in the ENDO and SURG groups, respectively (P = 0.15). Abdominal pain improved in 12 (52.2 %) ENDO and five (15.2 %) SURG patients
at 12 months (P = 0.007).
Table 3
Presence of symptoms associated with gastro-gastric fistula at 1 year.
|
Post-procedure characteristics
|
Endoscopy
(n = 45)
|
Surgery
(n = 45)
|
P value
|
|
Diabetes resolution[1] – n (%)
|
1 (9.1)
|
1 (6.3)
|
1.0
|
|
GERD improvement[1] – n (%)
|
7 (20.6)
|
2 (6.1 %)
|
0.15
|
|
Abdominal pain improvement[1] – n (%)
|
12 (52.2)
|
5 (15.2)
|
0.007
|
|
6-month weight change – lb
|
2.8 (10.4)
|
10.5 (7.8)
|
0.0005
|
|
6-month %TWL[2] – %
|
0.59 (5.7)
|
5.5 (3.9)
|
0.0002
|
|
12-month weight change[2] – lb
|
4.2 (18.8)
|
14.1 (14.9)
|
0.02
|
|
12-month %TWL[2] – %
|
1.9 (6.9)
|
6.2 (5.2)
|
0.007
|
Presented as mean (standard deviation) for normal variables.
†Median (interquartile range) for non-normal variables. Fisher’s exact test performed
for categorical variables and Wilcoxon Rank Sum test performed for non-normal continuous
variables (weight change).
1 Calculated at 12 months using number of patients with initial symptoms in each cohort
as shown in Table 1.
2 Median (interquartile range) for non-normal variables. Fisher’s exact test performed
for categorical variables and Wilcoxon Rank Sum test performed for non-normal continuous
variables (weight change).
At 6 months, 35 (78 %) of the ENDO group and 40 (89 %) of the SURG group stopped gaining
weight (P = 0.23) with the ENDO and SURG groups experiencing 0.59 % and 5.5 % total weight
loss (TWL) (P = 0.0002), respectively ([Table 3]). At 12 months, 59 % of the ENDO group and 93 % of the SURG group stopped gaining
weight (P = 0.007) with the ENDO and SURG groups experiencing 1.9 % and 6.2 % TWL (P = 0.007), respectively.
Treatment-related AEs occurred in four (8.9 %) ENDO and 16 (35.6 %) SURG patients
(P = 0.005) ([Table 4]). Among treatment-related AEs, none and eight (17.8 %) were serious (severe) in
the ENDO and SURG groups, respectively (P = 0.006). Treatment-related SAEs in the SURG group included leak (4), abdominal hernia
(3), abscess (3), severe abdominal pain (3), gastrointestinal bleeding (1), small
bowel obstruction (1) and gastrojejunal anastomotic stricture (1). Among AEs, the
open surgical technique was associated with three abdominal hernias, two leaks, one
severe abdominal pain and one small bowel obstruction. The remainder of AEs in the
surgical group occurred using the laparoscopic technique.
Table 4
Treatment-related adverse events over 12-month follow-up duration.
|
Treatment-related adverse events
|
Endoscopy
(n = 45)
|
Surgery
(n = 45)
|
P value
|
|
Overall treatment-related adverse events – n (%)
|
4 (8.9)
|
16 (35.6)
|
0.005
|
|
|
3 (6.7)
|
0
|
|
|
1 (2.2)
|
3 (6.7)
|
|
|
0
|
4 (8.9)
|
|
|
0
|
3 (6.7)
|
|
|
0
|
1 (2.2)
|
|
|
0
|
1 (2.2)
|
|
|
0
|
1 (2.2)
|
|
|
0
|
3 (6.7)
|
|
Serious treatment-related adverse events – n (%)
|
0
|
8 (17.8)
|
0.006
|
Treatment-related adverse events observed during the 12-month follow-up duration following
treatment for gastro-gastric fistula.
Discussion
GGF is an uncommon late complication following RYGB; however, it is associated with
undesirable symptoms of recurrence or onset of diabetes, abdominal pain, acid reflux
and weight regain [7]. Subsequently, repair through either endoscopic or surgical approaches is often
required. The present study is currently the largest study directly comparing the
efficacy and safety of endoscopic to surgical treatment of GGF in RYGB patients.
The endoscopic approach was associated with similar rates of diabetes and GERD improvement,
higher rates of abdominal pain improvement, but with a lower AE rate compared to surgical
revision. The difference in abdominal pain may at least be in part due to differences
in AE rates, particularly given that only severe treatment-related AEs occurred within
the surgical group. In addition, the endoscopic approach avoids the need for de novo
incisions that are required with the surgical approach, reducing additional potential
pain sources.
Treatment-related AEs occurred four-fold more frequently in the surgical repair (n = 16;
35.6 %) as compared to endoscopic (n = 4; 8.9 %) group and serious (severe) treatment-related
AEs only occurred in the surgery group. The observed complications differed between
groups and likely related to procedural approach, which may have contributed to the
magnitude of weight loss in either group, particularly the surgical group based on
the character of treatment-associated AEs. Marginal ulceration (3) and severe abdominal
pain (1) were observed in the endoscopic repair group, which may be the result of
localized tissue ischemia from tissue approximation. An increased rate of surgical
complications following surgical repair is expected given the invasive nature in comparison,
particularly when using the open surgical approach. Leak (4), abdominal hernia (3),
abscess (3), severe abdominal pain (3), gastrointestinal bleeding (1), small bowel
obstruction (1) and gastrojejunal anastomotic stricture (1) observed were similar
to previous studies [9]. Furthermore, these treatment-related AEs may have contributed to the greater amount
of weight loss seen in the surgical group at 6 and 12 months.
The magnitude of weight loss achieved over 1 year following surgical GGF repair in
this study (14.1 lb; 6.4 kg) is also similar to prior studies evaluating surgical
GGF repair (13.7 lb; 6.0 kg) [16]. This may be partially attributable to fistula size (15 ± 9mm) being more amenable
to surgical repair, as prior studies have demonstrated GGF size < 10 mm diameter is
associated with better outcomes following endoscopic repair [11]. A notable limitation historically with endoscopic intervention is instrument size,
which is restricted to allow passage through the transoral approach. This requires
utilization of a variety of smaller-scale methods to achieve fistula repair, such
as endoscopic clipping, fibrin glue or gastroplication [11]
[17]. Notably, although the present study incorporated a variety of repair methods including
combinations of APC, ESD, gastroplication, endoscopic suturing, clips, fibrin glue
and stent, there were no statistically significant differences in symptom resolution
or weight changes when stratifying by endoscopic suturing and other repair methods.
This lends credence to the individualized approach that should be pursued when endoscopically
treating GGF, as they can vary in size and location. Although an algorithmic approach
toward treating GGF is desired, the variable characteristics (i. e. size, number,
tissue quality and location) of GGFs requires an individualized approach to treatment,
particularly as new devices emerge. In contrast, surgical repair allows the introduction
of larger instruments to permit GGF repair with staple closure [18], excision [9], RYGB/gastrojejunal anastomosis revision or partial gastrectomy [19], where ultimately fistula resection may provide a more definitive treatment.
There are a few limitations to the present study. This was a retrospective cohort
study and, therefore, despite controlling for patient characteristics, residual confounding
remains possible. The patient population was also limited to two large tertiary referral
centers within a single region, limiting generalizability of results. However, this
likely reflects routine practice as referral to expert centers is common. In addition,
longer duration of follow-up would provide greater insight into the durability of
GGF treatment in either group, most notably that of weight trends, as GGF often leads
to weight gain.
Conclusions
In conclusion, endoscopic repair of GGF results in clinically and statistically fewer
overall and serious treatment-related AEs and greater resolution of abdominal pain
when compared to surgical repair. In contrast, surgical revision appears to yield
greater weight loss at 1 year.
