Introduction
Upper gastrointestinal bleed (UGIB) is the most common gastrointestinal-related reason
for hospitalization [1]. Peptic ulcer disease (PUD) is the most common cause of UGIB, accounting for 30 %
to 60 % of cases [2]
[3]
[4]. Endoscopic therapy is effective at stopping initial bleeding and reducing rates
of rebleeding, referral to surgery, and mortality [5]. A wide variety of conventional options for endoscopic management of bleeding PUD
exist, including injection therapy used in combination with a second endoscopic modality,
mechanical hemostasis with hemoclips, and thermocoagulation therapy (ie, heater probe
or bipolar electrocoagulation [6]
[7]. These are generally considered relatively effective as first-line therapy for hemostasis,
with rates of efficacy ranging from 54 % to 100 %, depending on the study and type
of intervention used [6]
[8].
However, persistent or recurrent bleeding of PUD remains a challenging clinical problem.
Studies have demonstrated that after undergoing endoscopic therapy for peptic ulcer
bleeding, the rate of rebleeding is up to 18 %, with mortality from rebleeding ranging
from 7 % to 9 % [5]
[9]
[10]. Furthermore, patients with difficult-to-manage rebleeding may require emergent
referral to interventional radiology or surgery, with all of the attendant risks of
emergent proceduralization. Risk factors for rebleeding include severe anemia, shock,
ulcer size and Forrest classification, physical status scores, and delayed therapy
[5]
[9]
[10]. Finally, patients on anticoagulation or antiplatelet therapies pose a very high
risk for bleeding complications of PUD [11]
[12]
[13] including potentially a higher risk of rebleeding [14]
[15]. Thus, new endoscopic interventions for hemostasis are needed, especially in patients
who fail to respond to initial endoscopic therapy or who are at high risk for bleeding
complications.
Endoscopic suturing is a technique that was initially developed to close defects of
the wall of the gastrointestinal lumen, such as perforations, leaks, and fistulas.
Due to its excellent ability to close large mucosal defects, the endoscopic suturing
device has recently been described as a novel endoscopic modality for treatment of
UGIB [16]. However, data on the efficacy and safety of endoscopic suturing for management
of acute UGIB are lacking. Thus, the current study was undertaken to evaluate the
safety and effectiveness of endoscopic suturing for hemostasis of PUD-related UGIB.
Patients and methods
Study design and patient population
We performed an international, retrospective study of prospectively collected data
at three centers (2 United States, 1 Hong Kong) of all consecutive patients who underwent
endoscopic suturing for non-variceal acute UGIB between January 2015 and November
2017. It should be noted that in these instances, the endoscopic suturing device is
being used for an indication not currently approved by the United States Food and
Drug Administration (FDA). Institutional Review Board approval was obtained per local
protocol at each center. Excluded cases include those in which suturing was performed
for bleeding prophylaxis after endoscopic resection of a gastrointestinal tract lesion,
or for post-surgical patients with an anastomotic ulcer.
Data collection
All endoscopists who were involved in the study kept a record of all procedures, and
all suturing cases that met the above criteria, regardless of the results of the procedure,
were included in the current study. The electronic medical record was examined to
extract necessary data, including both the hospital record and the endoscopy reporting
software. Such data include demographic information; baseline clinical information
such as admission and nadir hemoglobin values; information on prior endoscopic procedures,
including number of procedures and type of intervention(s); use of any antiplatelet
and/or anticoagulation agents; and information on the index ulcer(s) that were sutured,
including ulcer size, Forrest classification, ulcer location; and presence of carcinoma
on gastric biopsy (if performed). In addition, data on the suturing procedure itself
were recorded, including number of sutures used, time of procedure, any early or delayed
adverse events (AEs), length of procedure, and technical success or failure of the
procedure. Finally, post-procedure information including information on any follow-up
endoscopy procedures, length of follow-up, and history of rebleeding after the suture
procedure, were included as well. This study also included three patients that were
previously published as a case series with updated follow-up outcomes data provided
[16].
Procedure
Endoscopic suturing of the peptic ulcer was performed ([Fig. 1] and [Fig. 2]), as previously described [16]. In brief, the suturing device (OverStitch; Apollo Endosurgery, Austin, Texas, United
States) was mounted on a therapeutic double-channel upper Olympus GIF-2TH180 endoscope
(Olympus America, Center Valley, Pennsylvania, United States). A suture anchor with
a detachable needle was passed through one accessory channel and connected to the
suturing arm of the suturing device. The handle portion was attached to the endoscope.
The scope preloaded with the endoscopic suturing system was inserted into the stomach.
Full-thickness bites were taken at the normal mucosa through the gastric wall for
each bite. A figure-of-eight suture pattern was used to oversew the ulcer with bites
being taken approximately 5 mm away from the ulcer edge. After tightening the suture,
a cinch was used to secure the deployed suture [Video 1]. One or more 2 – 0 polypropylene suture(s) were used. The number of sutures placed
was determined at the discretion of the performing endoscopist.
Fig. 1 Endoscopic suturing patterns. Running suture (left) and figure-of-eight suture (right).
Fig. 2 Endoscopic suturing of peptic ulcer. Endoscopic suturing procedure. a A 2-cm ulcer located in lesser curvature of gastric body prior to suture. b Use of endosuturing device. c After oversewing of the ulcer.
Video 1 Demonstration of endoscopic suturing device to sew a peptic ulcer.
Outcomes
The primary outcome was the technical success of the procedure, defined as successful
deployment of one or more endoscopic sutures in the desired area. Secondary outcomes
included early rebleeding, defined as bleeding within 72 hours after endoscopic suturing;
delayed rebleeding, defined as bleeding between 72 hours and up to 30 days after treatment;
the need for surgery or angio-embolization; and finally, the rate of AEs associated
with the index procedure. AEs were defined based on previously established criteria
by the American Society of Gastrointestinal Endoscopy [17].
Statistical analysis
All statistical analyses were conducted using Microsoft Excel (Version 2011, Redmond,
Washington, United States). Descriptive statistics for the study population as well
as the outcomes of interest were generated. For categorical variables, frequencies
and percentages (%) are reported. Means with standard deviations (±) or medians with
interquartile ranges (IQR) are reported for continuous variables.
Results
Patient population and pre-procedure information
A total of 10 patients (mean age 66.7 years, 30 % female) were included in the study.
The clinical presentation was melena in six, hematemesis in two, and both hematemesis
and melena in two. Prior to endoscopic hemostasis, twice-a-day proton pump inhibitor
was given to all patients. Average lowest pre-endoscopy hemoglobin was 8.1 mg/dL (range
3.1 – 12.8). Reasons for endosuturing included bleeding refractory to standard endoscopic
therapy in nine (90 %) and a very large ulcer with severe bleeding in one (10 %).
Nine (90 %) had prior endoscopy therapy for UGIB prior to endoscopic suture, with
an average of 1.4 ± 0.7 (range, 1 – 3) endoscopic sessions. Among the therapeutic
modalities employed prior to the index suturing procedure, endoscopic clip(s) were
used in 4/9 (44.4 %), bipolar probe was used in one of nine (11.1 %), and epinephrine
injection in conjunction with either endoscopic clip(s) or bipolar probe was used
in four of nine (44.4 %). ([Table 1]).
Table 1
Patient and ulcer characteristics and procedural results.
|
Age/sex
|
Clinical presentation
|
Location of largest ulcer/size of the ulcer (mm)/ Forrest classification
|
Number of prior endoscopic therapy sessions before endosuturing
|
Reason for endoscopic suturing
|
Technical success/ number of sutures used
|
Immediate hemostasis
|
Early rebleeding (≤ 72 h)/Delayed rebleeding (> 72 h)/adverse events
|
|
78/male
|
Melena
|
Gastric body/30/Ib
|
None
|
High-risk rebleeding due to very large ulcer size (3 cm diameter)
|
Yes/4
|
Yes
|
No/no/no
|
|
74/male
|
Melena
|
Gastric body/20/IIa
|
1
|
Bleeding refractory to endoscopic hemostasis
|
Yes/1
|
Yes
|
No/no/no
|
|
57/male
|
Melena
|
Gastric body/30/IIa
|
2
|
Bleeding refractory to endoscopic hemostasis
|
Yes/2
|
Yes
|
No/no/no
|
|
32/female
|
Melena
|
Pylorus/15/Ib
|
2
|
Bleeding refractory to endoscopic hemostasis
|
Yes/1
|
Yes
|
No/no/no
|
|
76/male
|
Hematemesis
|
Proximal lesser curvature of gastric body/20/IIc
|
3
|
Bleeding refractory to endoscopic hemostasis. High risk rebleeding due to history
of rebleeding, and large ulcer size and recent cardiovascular event required uninterrupted
dual antiplatelet therapy
|
Yes/1
|
Yes
|
No/no/no
|
|
63/female
|
Melena
|
Anterior wall duodenum/20/Ib
|
1
|
Bleeding refractory to endoscopic hemostasis
|
Yes/1
|
Yes
|
No/no/no
|
|
89/male
|
Melena
|
Gastric body/30/IIa
|
1
|
Bleeding refractory to endoscopic hemostasis
|
Yes/2
|
Yes
|
No/no/no
|
|
64/male
|
Hematemesis and melena
|
Anterior wall duodenum/15/Ib
|
1
|
Bleeding refractory to endoscopic hemostasis
|
Yes/1
|
Yes
|
No/no/no
|
|
48/male
|
Hematemesis and melena
|
Prepyloric antrum/25/IIb
|
1
|
Bleeding refractory to endoscopic hemostasis
|
Yes/1
|
Yes
|
No/no/no
|
|
86/female
|
Hematemesis
|
Gastric cardia/15/Ib
|
1
|
Bleeding refractory to endoscopic hemostasis
|
Yes/1
|
Yes
|
No/no/no
|
Index ulcer
Bleeding sources were located in the gastric body in five, gastric cardia in one,
prepyloric antrum in one, pylorus in one, and the anterior wall of the duodenum in
two. Average size of the ulcer was 22 ± 6.3 mm (range 15 – 30). Forrest classification
of the ulcer was Ib in five (50 %), IIa in three (30 %), IIb in one (10 %), and IIc
in one (10 %). Biopsy was performed in seven of 10 cases; and cancer was not identified
in any of the seven biopsies.
Endosuture procedure and follow-up data
Immediate hemostasis was achieved in five of five patients (100 %) with Forrest Ib
ulcers. Technical success was 100 %. Mean suturing time was 13.4 ± 5.6 (range 3.5 – 20)
minutes. Mean number of sutures used was 1.5 (range 1 – 4). The hemoglobin value was
stable without additional transfusion in all patients. None of the patients experienced
early rebleeding. One patient was then lost to follow up, thus follow-up data were
available for nine patients at 30 days. Delayed recurrent bleeding was not observed
in any of these cases. Median length of long-term follow-up for these nine patients
was 11 months (range 2 – 56), and no additional gastrointestinal bleeding was reported
in any of these cases over the full long-term follow-up period.
No AEs were observed both in the early period for 10 of 10 patients or late period
for nine of nine patients with follow-up. Information on post-discharge EGD was available
in four patients (40 %) after a median of 1 month (IQR, 0.75 – 2.25) after the endosuturing
procedure. Of these, two had evidence of a small residual ulcer, two had a healed
ulcer, and the original suture(s) were intact in all four.
Discussion
In this pilot study, oversewing of a bleeding peptic ulcer using endoscopic suturing
appeared to be an effective method for achieving hemostasis for large, recurrent bleeding
peptic ulcers which are usually difficult to manage. No early or delayed bleeding
was noted in our series. Endoscopic suturing was technically successful in all cases,
including ulcers at the pylorus and duodenum, with no AEs. While our study presents
only a small sample size which will require validation in larger cohorts, our data
suggest that rescue endoscopic hemostasis using endoscopic suturing can be an alternative
option for treating nonvariceal UGIB when primary endoscopic hemostasis fails to control
the bleeding or when hemorrhage recurs after successful control of bleeding. We wish
to emphasize that for the indication for refractory or recurrent gastrointestinal
bleeding, this device and associated technique is still investigational and is not
FDA approved.
The endoscopic suturing device directs a suture through the lining of the stomach
or small intestine to bring two areas of mucosa and deeper wall layers in close apposition.
This procedure mimics the hemostatic suturing methods us surgically. In addition,
oversewing the ulcer could theoretically prevent exposure of the submucosal vessels
in the ulcer bed to gastric contents [18], thus potentially promoting healing of the ulcer and potentially decreasing risk
for recurrent bleeding. However, these are only theoretical mechanisms, and given
that two of four suture sites (50 %) seen on repeat endoscopy still had residual ulcer,
one can argue that use of sutures in this setting does not in fact have any inherent
advantage to promoting ulcer healing. Finally, it should be noted that a stitch that
is too tight would in fact promote ischemia and potentially worsen the healing process,
thus, extreme care must be taken in these cases.
In patients with clinical evidence of rebleeding, repeat endoscopic therapy is recommended
[19]. Conventional through-the-scope (TTS) clips or thermal therapy with either bipolar
electrocoagulation or heater probe are generally used. However, these treatment modalities
are not always successful at hemostasis. For a fibrotic ulcer base, application of
TTS clips is technically difficult, and repeated application of heater probe is associated
with risk of thermal injury and perforation. In fact, a meta-analysis suggested that
almost half of the perforations associated with thermal therapy occurred in patients
who underwent repeat treatment [8].
There are several new options for advanced endoscopic retreatment of bleeding peptic
ulcer disease, and the efficacy of these new endoscopic modalities, such as hemospray
and over-the-scope clips (OTSC), is also promising [20]
[21]. A brief comparison of the parameters to guide selection of these modalities provides
useful context about when endoscopic suturing should be considered. Hemospray is generally
considered a temporizing measure, rather than definitive treatment, for PUD-related
UGIB. Although hemospray is effective with a greater than 90 % rate of immediate hemostasis,
high rates of rebleeding up to 29 % to 38 % in benign nonvariceal UGIB have been reported
[22]
[23]. Thus, it is recommended as a bridge to more definitive treatment [22]
[24]. Use of OTSC is limited by ulcer size, because a large ulcer would not be amenable
to such therapy. Further, for deep or fibrotic ulcers, placement of OTSC is technically
difficult as the ulcer may not invert adequately into the cap and lead to clip misplacement
[25]. Thus, OTSC deployment should be used for small, shallow, and non-fibrotic ulcers.
Finally, advantages of endoscopic suturing compared to other endoscopic modalities
include its efficacy even for large ulcers in difficult locations such as high lesser
curvature and pylorus. Disadvantages include the need for a double channel endoscope
and the requirement for extensive expertise and training in performing the suturing
procedure. Performing endoscopic suturing in retroflexion can be challenging given
difficult scope maneuverability and limited visualization. Use of the tissue helix
along with rotation of the scope may aid in accomplishing suturing on the retroflexed
position. Another concern is the risk that suturing could close and hide a carcinomatous
ulcer. It is advisable to avoid endosuturing if there is a suspicion of malignant
ulcer. We biopsy gastric ulcers prior to endosuturing and recommend follow-up endoscopy
to assess ulcer healing. In the setting of persistent, non-healing gastric ulcer,
biopsy should also be obtained of at the follow-up endoscopy.
Although angioembolization of a targeted bleeding vessel has a high technical success
rate, clinical success rates for this procedure are below 80 % [20] and associated AEs, such as small bowel ischemia or stricture, hepatic infarct,
access site hematoma and pseudoaneurysms, are reported as high as 26 % [26]. Surgical management of PUD such as ulcer exclusion and vagotomy are associated
with surgical morbidities and mortality. In both surgical and angioembolization procedures,
recurrent bleeding has been shown to occur in about one-quarter of cases with high
rates of subsequent reproceduralization at 20 % [21]. Thus, use of rescue endoscopic methods such as endosuturing may play a role in
therapy of UGIB.
To our knowledge, this study represents the largest series of patients who have undergone
endoscopic suturing for a bleeding peptic ulcer. Limitations include its small sample
size and its retrospective nature. In addition, the endosuturing technique was not
standardized and there may be minor variations in technique used. Further, this procedure
was performed by highly experienced endoscopists with training in advanced procedures,
resulting in a short procedure time and a high success rate, and the results may not
be generalizable.
Conclusion
In conclusion, endoscopic suturing for acute UGIB has a high technical success rate
as well as desirable clinical results of hemostasis and prevention of recurrent bleeding.
This modality represents a useful adjunct to the therapeutic armamentarium as a rescue
therapy for refractory bleeding that has failed standard endoscopic hemostasis. Further
research is needed to validate our results as well as determine its superiority relative
to other endoscopic hemostatic modalities.
