Introduction
The small intestine has long been a challenge for gastroenterologists to examine using
traditional endoscopic and radiologic techniques. The development of capsule endoscopy
and balloon assisted enteroscopy (BAE) allows direct visualization of the entire small
bowel with comparable diagnostic yields [1 ]
[2 ]. Whereas video capsule endoscopy (VCE) is limited to purely diagnostic ability,
BAE allows histopathological diagnosis and treatment [3 ]
[4 ]. While VCE is generally the preferred initial diagnostic test because it is less
invasive and more cost-effective, it is reasonable to perform BAE first if biopsies
are needed or therapeutic intervention is probable [5 ]
[6 ]
[7 ]
[8 ]
[9 ]
[10 ].
The development of techniques allowing deep enteroscopy has drastically impacted our
approach to the diagnosis and management of patients with obscure gastrointestinal
bleeding (OGIB). OGIB is the most common indication for enteroscopy and is defined
as occult or overt bleeding of unknown origin that persists or recurs after an initial
negative evaluation with bidirectional endoscopy [11 ]
[12 ]
[13 ]
[14 ]. This technology has largely replaced conventional barium studies and intraoperative
enteroscopy [15 ]. Although less data has been published with regard to single balloon enteroscopy
(SBE) outcomes compared with double balloon enteroscopy (DBE), as it is a newer technology,
multiple studies have shown the two devices to be comparable [12 ]
[13 ]
[14 ]
[16 ]
[17 ]
[18 ]
[19 ]
[20 ]
[21 ]. Our institution uses SBE for evaluation and therapeutic intervention of suspected
small-bowel disorders. Currently, there is no consensus on the timing of enteroscopy
in the evaluation of OGIB. The goal of this study was to determine whether there was
an increased diagnostic or therapeutic yield of SBE performed emergently (within 24
hours of hospitalization) as opposed to non-emergently (more than 24 hours after admission)
in patients with OGIB. To our knowledge, this study provides the largest cohort of
patients undergoing SBE to evaluate OGIB in a single center.
Materials and methods
Definition
In this study, we evaluated patients with overt bleeding and occult bleeding that
developed with or without recurrence after initial negative esophagogastroduodenoscopy
(EGD) and colonoscopy [11 ]. Overt bleeding was defined as visible gastrointestinal bleeding of unknown origin.
Occult bleeding was gastrointestinal blood loss without visible bleeding defined by
iron deficiency anemia or a positive fecal occult blood test. An emergent SBE was
defined as SBE performed within 24 hours of hospitalization whereas non-emergent SBE
was defined as SBE performed more than 24 hours after admission. The timing of endoscopy,
emergent or non-emergent, was a clinical decision made by the endoscopist based on
the patient’s presentation and clinical status. VCE was not always performed immediately
before enteroscopy, depending on the clinical setting. Capsules were not performed
in the setting of a patient with an enteroscopy performed within 24 hours. This typically
included patients with a high clinical suspicion for small-bowel pathology such as
a history of known small-bowel arteriovenous malformations (AVMs), recent EGD or colonoscopy
performed without yield, or positive nuclear medicine bleeding scans.
Patients
We obtained Institutional Review Board approval from the University of South Florida
and Tampa General Hospital. Between January 2010 and August 2013, a total of 428 SBEs
were performed on 377 patients with suspected small-bowel diseases. Of those patients,
110 consecutive hospitalized patients with obscure gastrointestinal bleeding were
retrospectively reviewed. The other 267 patients underwent SBE as an outpatient or
for non-bleeding indications and were excluded. Outpatients were not included, as
this would lead to bias, because non-hospitalized patients typically do not carry
the same morbidity as hospitalized patients. Basic demographic information was collected,
which consisted of age, sex, and prior abdominal surgery. Length of hospital stay,
hemodynamic characteristics, American Society of Anesthesiologists (ASA) physical
classification system, type of obscure bleed, and need for emergent intervention were
recorded. Hemodynamic characteristics included lowest reported hemoglobin, the need
for transfusion, and units of blood transfused. Emergent intervention included procedures
performed by surgery or interventional radiology. Endoscopic reports were examined
for enteroscopy approach, location of lesion, type of lesion identified, therapeutic
intervention performed, and adverse events.
SBE procedure
A SIF-Q180 enteroscope (Olympus Medical, Center Valley, PA, United States) was used
to examine the small intestine according to the standard push-and-pull technique.
SBE was performed by one of four experienced endoscopists with well over 100 SBEs
per endoscopist. Training included either an advanced endoscopy fellowship and/or
expertise using push enteroscopy before SBE. The initial approach to SBE was determined
by clinical symptoms and findings on imaging or VCE. The oral approach was chosen
first in patients with melena or localization of a lesion in the first 75 % of the
small bowel. The anal approach was chosen first in patients with hematochezia or evidence
of a lesion in the distal 25 %. If clinical suspicion was high despite negative findings
on the initial insertion route, a submucosal tattoo was placed to mark the deepest
insertion point, and the other enteroscopic route was performed. Air insufflation
was used in the majority of cases secondary to limited carbon dioxide availability.
Overnight fasting was required of all patients. Additionally, those who underwent
the retrograde approach received a bowel preparation with 4 L of polyethylene glycol
electrolyte lavage solution the day before examination. Informed consent was obtained
from each patient before the procedure. All procedures were performed under monitored
anesthesia care using intravenous propofol administered by an anesthesiologist or
nurse anesthetist.
Assessment of endoscopic findings
The location of the lesion was documented as occurring in the duodenum, jejunum, or
ileum. We categorized the source of small-bowel bleeding as an erosion, ulcer, stricture,
angiodysplasia/arteriovenous malformation (AVM), polyp, mass, Dieulafoy’s lesion,
varix, or other. The category “other” encompassed erythematous mucosa, a pigmented
lesion, or an active bleeding site with no lesion identified. We did not consider
lymphangiectasia to be a bleeding source.
Endoscopic treatment
Therapeutic intervention included argon plasma coagulation, multipolar electrocautery
(Gold Probe), clipping, dilation, polypectomy, or dual therapy.
Statistical analysis
The association between dependent and independent variables was assessed using either
an independent samples t test for continuous variables or Fisher’s exact test for binary variables. For continuous
data, the results were summarized as mean difference (MD) and 95 % confidence intervals
(CI). For dichotomous data, results were summarized using odds ratio (OR) and 95 %CI.
Bonferroni correction was applied to adjust for multiple comparisons. P values less than 0.05 were considered to be statistically significant. All data analyses
were performed using SPSS v22 software.
Results
Demographic and clinical characteristics
Our study included 110 consecutive hospitalized patients with obscure gastrointestinal
bleeding who underwent SBE. Patients were divided into two groups based on procedures
performed emergently (within 24 hours) versus non-emergently (more than 24 hours).
Enteroscopy was performed emergently in 30 patients (27 %) and non-emergently in 80
patients (73 %). VCE was not performed before enteroscopy in the emergent group. In
the non-emergent group, 57.5 % (46 /80) underwent VCE initially. Patient demographics
and hemodynamic characteristics are shown in [Table 1 ]. Mean age, gender, history of abdominal surgery, and ASA class were similar between
the two groups. The majority of our patients in both groups were classified as ASA
class III. Hospital stay was statistically significantly shorter in the patients who
had SBE within 24 hours of admission versus after 24 hours (6.2 vs. 11.3 days, respectively;
P < 0.001). There was no statistically significant difference between groups with regard
to lowest reported hemoglobin, the need for transfusion, and units of blood transfused.
Table 1
Demographic and hemodynamic characteristics of hospitalized patients with obscure
gastrointestinal bleeding who underwent single balloon enteroscopy emergently (< 24
hours) versus non-emergently (≥ 24 hours).
< 24 hours (n = 30)
≥ 24 hours (n = 80)
OR (95 %CI) or MD (95 %CI)
P value
Age, y
63.1 ± 13.4
65.1 ± 14.3
– 2.06 ( – 7.9, 3.8)
0.48
Sex (female : male)
14/30 (46.7 %)
35/80 (43.8 %)
1.13 (0.49, 2.61)
0.78
History of abdominal surgery
14/30 (46.7 %)
34/80 (42.5 %)
1.18 (0.51, 2.8)
0.70
Days hospitalized
6.2 ± 5.7
11.3 ± 9.0
– 5.09 ( – 8.0, – 2.1)
0.001
ASA status
2.93 ± 0.640
3.00 ± 0.585[* ]
– 0.067 ( – 0.323, – 0.190)
0.61
Lowest hemoglobin reported, g/dL
8.7 ± 2.3
8.7 ± 2.2
0.03 ( – 1.05, 1.11)
0.96
Transfusions
17/30 (56.7 %)
41/80 (51.2 %)
1.24 (0.53, 2.90)
0.61
Emergent intervention (surgical or radiological)
3/30 (10.0 %)
0/80 (0 %)
20.49 (1.03, 409.37)
0.019
Units transfused
1.93 ± 2.31
2.3 ± 2.9
– 0.33 ( – 1.42, 0.75)
0.55
Values in italics are statistically significant (P < 0.05).
* In the ≥ 24-hour group, ASA score was only able to be obtained in 77 of 80 patients.
Patients in the group where enteroscopy was performed within 24 hours versus greater
than 24 hours had a significantly higher incidence of radiological intervention (10.0 %
vs. 0.0 %, respectively; P = 0.019). Interventions included placement of an inferior vena cava (IVC) filter
in a patient with a newly discovered clot and active gastrointestinal bleeding, pullback
cholangiogram and replacement of an internal/external biliary drainage catheter in
a patient with hemobilia induced by the initial drain, and placement of a gastrostomy
tube for gastric decompression in a patient with a duodenal mass. The patient requiring
an IVC filter was bleeding secondary to an AVM. The patient with hemobilia was presumed
to be bleeding from a hepatic artery injury caused by placement of the initial drain.
The patient with a duodenal mass requiring gastrostomy tube placement had no identified
source of bleed.
Characteristics of SBE
Characteristics of SBE are displayed in [Table 2 ]. We examined the small intestine via the oral approach in 29 patients in the emergent
group and 69 patients in the non-emergent group and via the anal approach in two patients
in the emergent group and 13 patients in the non-emergent group. This included one
patient in the emergent group and two patients in the non-emergent group who were
examined via both oral and anal approaches (total enteroscopy). There was no significant
difference in antegrade or retrograde approach between groups. When obscure bleeds
were further broken up into overt and occult bleeding, there was no statistically
significant difference with regard to timing of enteroscopy.
Table 2
Diagnostic yield, therapeutic yield, enteroscopy approach, and adverse events of hospitalized
patients with obscure gastrointestinal bleeding who underwent single balloon enteroscopy
emergently (< 24 hours) versus non-emergently (≥ 24 hours). The diagnostic and therapeutic
yields were calculated for all patients in each group as well as for overt and occult
bleeding individually.
< 24 hours (n = 30)
≥ 24 hours (n = 80)
OR (95 %CI) or MD (95 %CI)
P value
Diagnostic yield
16/30 (53.3 %)
50/80 (62.5 %)
0.69 (0.29, 1.6)
0.38
Therapeutic yield
9/30 (30 %)
34/80 (42.5 %)
0.58 (0.24, 1.4)
0.23
Overt
21/30 (70 %)
42/80 (52.5 %)
2.11 (0.86, 5.2)
0.10
Diagnostic yield
11/21 (52.4 %)
26/42 (61.9 %)
0.68 (0.24, 1.95)
0.47
Therapeutic yield
6/21 (28.6 %)
21/42 (50 %)
0.40 (0.13, 1.23)
0.11
Occult
9/30 (30 %)
38/80 (47.5 %)
0.47 (0.19, 1.16)
0.10
Diagnostic yield
5/9 (55.6 %)
24/38 (63.2 %)
0.73 (0.17, 3.17)
0.67
Therapeutic yield
3/9 (33.3 %)
13/38 (34.2 %)
0.96 (0.21, 4.5)
0.96
Anterograde approach
29/30 (96.7 %)
69/80 (86.2 %)
4.62 (0.57, 37.5)
0.15
Retrograde approach
2/30 (6.7 %)
13/80 (16.2 %)
0.37 (0.08, 1.74)
0.21
Adverse events
2/30 (6.7 %)
1/80 (1.2 %)
0.18 (0.02, 2.03)
0.16
Diagnostic yield
The diagnostic yield was determined in the emergent and non-emergent groups for all
bleeds, and for overt and occult bleeds individually ([Table 2 ]). Among the 30 patients who underwent emergent enteroscopy, 16 were identified as
having potential sources of small intestinal bleeding, for an overall diagnostic yield
of 53.3 %. When further broken down by type of obscure bleed, the diagnostic yield
was 52.4 % (11/21) for overt bleeds and 55.6 % (5/9) for occult bleeds. For the 80
patients in the non-emergent group, 50 had a potential bleeding source, for a diagnostic
yield of 62.5 %. Of those 50 patients, the diagnostic yield was 61.9 % (26/42) for
overt bleeds, and 63.2 % (24/38) for occult bleeds. There was no statistically significant
difference in diagnostic yield when comparing emergent and non-emergent SBE for all
OGIB or overt versus occult individually.
Therapeutic yield
Similarly, the overall therapeutic yield and the therapeutic yield for overt and occult
bleeding were calculated in the emergent and non-emergent groups ([Table 2 ]). In the emergent group, 9/30 patients had therapeutic intervention, for an overall
therapeutic yield of 30 %, with a therapeutic yield of 28.6 % (6/21) for overt bleeds
and 33.3 % (3/9) for occult bleeds. Non-emergently, 34/80 patients underwent therapeutic
maneuvers, for an overall therapeutic yield of 42.5 %, with a therapeutic yield of
50 % (21/42) for overt bleeds and 34.2 % (13/38) for occult bleeds. The therapeutic
yield between the two groups was not significantly different for all OGIB or by type
of obscure bleeding specifically.
Enteroscopy findings and therapeutic intervention
Location of isolated lesions was similar between the emergent and non-emergent groups,
as summarized in [Fig. 1 ]. In both groups, lesions were most commonly found in the jejunum with the fewest
lesions in the ileum. The potential bleeding sources are displayed in [Table 3 ]. When findings were present, bleeds were most likely due to ulcer (23.3 %) when
performed emergently and angiodysplasia/AVM (30.0 %) when performed non-emergently.
Lesions outside the small bowel as possible sources of gastrointestinal bleeding were
found in 21 of the 110 patients (19.1 %). This included three patients with two different
types of lesions, totaling 24 lesions detected. Findings included ulcer (n = 4), Cameron’s
lesions (n = 2), gastric antral vascular ectasias (n = 3), erosive gastritis (n = 8),
and angiodysplasia/AVM (n = 7). Therapeutic interventions are shown in [Fig. 2 ]. Argon plasma coagulation and multipolar electrocautery were the primary modalities
in both groups.
Fig. 1 Location of small-bowel lesions in hospitalized patients with obscure gastrointestinal
bleeding who underwent single balloon enteroscopy emergently (< 24 hours) versus non-emergently
(> 24 hours).
Table 3
Type of lesion identified in hospitalized patients with obscure gastrointestinal bleeding
who underwent single balloon enteroscopy emergently (< 24 hours) versus non-emergently
(≥ 24 hours).
< 24 hours (n = 30)
≥ 24 hours (n = 80)
OR (95 %CI) or MD (95 %CI)
P value
Erosion
1/30 (3.3 %)
5/80 (6.2 %)
0.52 (0.06, 4.62)
0.56
Ulcer
7/30 (23.3 %)
14/80 (17.5 %)
1.44 (0.52, 4.00)
0.49
Stricture
1/30 (3.3 %)
4/80 (5.0 %)
0.66 (0.07, 6.10)
0.71
Angiodysplasia/AVM
5/30 (16.7 %)
24/80 (30.0 %)
0.47 (0.16, 1.36)
0.16
Polyp
2/30 (6.7 %)
8/80 (10 %)
0.64 (0.13, 3.22)
0.59
Mass
0/30
1/80 (1.2 %)
N/A
N/A
Dieulafoy’s lesion
2/30 (6.7 %)
0/80
N/A
N/A
Varix
0/30
2/80 (2.5 %)
N/A
N/A
Other
2/30 (6.7 %)
13/80 (16.2 %)
0.37 (0.08, 1.74)
0.21
Negative
11/30 (36.7 %)
26/80 (32.5 %)
1.20 (0.50, 2.89)
0.68
AVM, arteriovenous malformation.
Fig. 2 Therapeutic interventions performed in hospitalized patients with obscure gastrointestinal
bleeding who underwent single balloon enteroscopy emergently (< 24 hours) versus non-emergently
(> 24 hours).
Adverse events
Adverse events were seen in three patients with no significant difference in the emergent
and non-emergent groups, as seen in [Table 2 ]. In the emergent group, two patients had adverse events secondary to transient hypoxia
in one patient and shortness of breath, hypertension, and hyperglycemia warranting
intensive care unit admission in the other patient. In the non-emergent group, one
patient had mucosal trauma secondary to the overtube.
Discussion
Review of the literature yields limited data with regard to the role of emergent SBE
in the evaluation of OGIB [22 ]
[23 ]. Overall, there is limited data with regard to either emergent DBE or SBE to evaluate
any symptomology. A small retrospective analysis of 10 patients by Mönkemüller et
al. showed emergency DBE to be feasible and beneficial in facilitating diagnosis and
therapy in OGIB [24 ]. Aniwan et al. looked specifically at patients with overt bleeding and found higher
diagnostic and therapeutic yields when DBE was performed within 72 hours [25 ]. There are no similar studies evaluating the timing of DBE for both overt and occult
gastrointestinal bleeding.
Regarding SBE, one recent study evaluated the impact of emergency SBE on the diagnosis
and treatment of active overt OGIB. Pinto-Pais et al. retrospectively reviewed 43
patients with overt OGIB and subsequently divided them into active-overt and inactive-overt
bleeders who underwent emergency and elective SBE, respectively [26 ]. Emergency SBE was defined as endoscopy performed within 24 hours of clinical presentation.
Patients with occult OGIB were excluded. They found a significantly higher diagnostic
yield in the emergency SBE group compared to the elective SBE group, 83.3 % vs. 64.3 %
(P = 0.038).
Currently, there is no consensus on the timing of enteroscopy in the evaluation of
OGIB. While emergent has yet to be defined, Mönkemüller et al. and Pinto-Pais et al.
suggested that the term applies to any procedure performed within 24 hours of clinical
presentation [24 ]
[26 ]. We, therefore, used 24 hours to define emergent endoscopy in our study.
Our study evaluated the impact of timing of SBE on the diagnostic yield, therapeutic
yield, need for surgical or radiological intervention, and adverse events for both
antegrade and retrograde enteroscopies. This data illustrates that patients in the
group where enteroscopy was performed within 24 hours had a significantly higher incidence
of radiological intervention (10.0 % vs. 0.0 %). The diagnostic and therapeutic yields
between the two groups were not significantly different. Interestingly, though not
statistically significant, the diagnostic and therapeutic yields were actually lower
in the emergent group, 53 % vs. 63 % and 30 % vs. 43 %, respectively. Our diagnostic
yields are comparable to other published studies (47 – 60 %) [12 ]
[13 ]
[27 ]
[28 ]. Variation in results was likely due to differences in inclusion criteria. Some
studies included non-bleeding indications and/or both inpatients and outpatients [12 ]
[27 ]
[28 ]. Furthermore, only one study analyzed therapeutic yield in patients who underwent
SBE to evaluate OGIB specifically [13 ]. Ramchandani et al. performed therapeutic intervention in 40 % (16/40) of patients,
with our study showing therapeutic yields of 30 % and 43 % in the emergent and non-emergent
groups, respectively.
Of the patients requiring radiological intervention, AVM was the cause of bleeding
in one patient with no lesion identified in the other two patients. Interventions
included IVC filter placement, replacement of a biliary drainage catheter, and gastrostomy
tube placement. The radiological interventions necessary were incidental and unrelated
to whether or not enteroscopy was performed. There was no significant difference in
adverse events with regard to timing of enteroscopy.
The secondary aim of this study was to compare patient demographics, ASA status, hemodynamic
characteristics, type of obscure bleed, lesions identified, location of lesions, and
endoscopic intervention performed between groups. Patient demographics (mean age,
gender, and history of abdominal surgery), ASA status, hemodynamic characteristics
(lowest reported hemoglobin, the need for transfusion, and units of blood transfused),
and type of obscure bleed (overt vs. occult) were similar between the two groups.
In both groups, lesions were most commonly found in the jejunum. When findings were
present, bleeds were most likely due to ulcer (23.3 %) when performed emergently and
angiodysplasia/AVM (30.0 %) when performed non-emergently, similar to other published
studies on both DBE and SBE [12 ]
[13 ]
[27 ]
[28 ]
[29 ]. Only one mass, pathologically consistent with lipoma, was detected. We did not
find any gastrointestinal stromal tumors (GISTs) or neuroendocrine tumors (NETs),
likely because GISTs and NETs typically cause other symptoms aside from bleeding.
Argon plasma coagulation and multipolar electrocautery were the primary modalities
in both groups. Hospital stay was significantly shorter in the patients who had SBE
within 24 hours of admission versus after 24 hours (6.2 vs. 11.3 days). This may be
due to earlier diagnosis with earlier application of endoscopic and/or medical therapy,
and earlier stabilization of hemoglobin levels.
Our study was limited due to its single center retrospective nature and small population
size. There were a lower number of patients in the urgent group than in the non-urgent
SBE group. This could be related to the variable reasons for hospital admission, with
only a portion of the cohort initially presenting with OGIB. The majority of cases
were anterograde based on clinical findings or imaging. Our study did not include
long-term follow-up, therefore we cannot assess the extended impact of intervention
on rebleeding rates with SBE. The strengths of our study include the evaluation of
SBE in regards to timing of overt and occult bleeding, something not reported previously.
This study was also performed by experienced gastroenterologists, with over 100 SBEs
performed before the study.
Conclusion
This is the first study to evaluate the impact of timing of SBE, emergent (within
24 hours) versus non-emergent (greater than 24 hours), in hospitalized patients with
OGIB. One prior study retrospectively evaluated active overt bleeds only [26 ]. This is the first study to include occult bleeders. It is also the largest cohort
of patients who underwent SBE to evaluate OGIB in a single center reported to date.
Currently, there is no consensus on the optimal timing of SBE in patients with obscure
bleeding. Although patients in the group where enteroscopy was performed within 24
hours had a significantly higher incidence of radiological intervention, these occurrences
were unrelated to whether or not enteroscopy was performed. The diagnostic and therapeutic
yields between the two groups were not significantly different, however, the emergent
SBE group had a significantly shorter hospital stay, which may be related to earlier
diagnosis and therapy. This suggests that, while endoscopists may not necessarily
need to perform emergent assessment within 24 hours in patients with OGIB for greater
diagnostic or therapeutic yield, early intervention does allow for earlier stabilization
of hemodynamics and thus shorter hospital stays. Prospective studies further evaluating
these findings are indicated.
