Abbreviations
A:
anterograde
Afib:
atrial fibrillation
APC:
argon plasma coagulation
AS:
aortic stenosis
ASA:
aspirin
AVM:
arteriovenous malformation
AVR:
aortic valve replacement
BAE:
balloon assisted enteroscopy
C:
colonoscopy
CABG:
coronary artery bypass graft
CHF:
congestive heart failure
COPD:
chronic obstructive pulmonary disease
CVA:
cerebral vascular accident
DBE:
double-balloon enteroscopy
DL:
Dieulafoy lesion
DM:
diabetes mellitus
EGD:
esophagogastroduodenoscopy
Epi:
epinephrine injection
GERD:
gastroesophageal reflux disease
HLD:
hyperlipidemia
HTN:
hypertension
IR:
interventional radiology embolization
MI:
myocardial infarction
MR:
mitral regurgitation
N/A:
data not available or missing
N/P:
not performed
OGIB:
obscure gastrointestinal bleeding
OSA:
obstructive sleep apnea
PPI:
proton pump inhibitor
PPM:
permanent pacemaker
PUD:
peptic ulcer disease
SBCE:
wireless small-bowel capsule endoscopy
SBE:
single-balloon enteroscopy
TR:
tricuspid regurgitation
W:
white
Introduction
Secondary to the lack of clear pathology evident until after surgery or autopsy, the
small bowel has been considered the “black box” of the gastrointestinal tract. In
the 1980’s push enteroscopy was developed allowing examination and endoscopic therapy
of the proximal jejunum [1 ]. In 2001 the small bowel capsule endoscopy (SBCE) finally made identification of
the culprit lesion, responsible for chronic or acute bleeding in the small bowel,
possible in a less invasive manner [2 ]. Unfortunately SBCE is only diagnostic and does not allow biopsies or treatment.
Balloon assisted enteroscopy (BAE) using either a single or double-balloon technique
opened the door for possible visualization of the entire small bowel tract with the
ability to treat or biopsy previously unreachable areas. When both anterograde and
retrograde routes are used successively, a “total” enteroscopy has been reported in
up to 86 % of patients [3 ]. However, more modest rates have been reported in three randomized controlled trials
where complete enteroscopies reportedly ranged from 0 % to 22 % in SBE and 18.5 %
to 66 % in DBE (RR, 1.73; 95 %CI, 0.86 – 3.48; P = 0.12) [4 ]
[5 ]
[6 ].
Dieulafoy lesion (DL) is a recognized cause of gastrointestinal bleeding since the
first reported case in the late 1800 s [7 ]. It accounts for up to 5 % of all instances of acute upper gastrointestinal bleeds
[8 ]. DLs are found throughout the gastrointestinal tract, but are usually located in
the proximal stomach along the lesser curvature. Rarely, these lesions may be found
in the small bowel and present an anatomical dilemma secondary to the inability to
reach these lesions by esophagogastroduodenoscopy (EGD) or colonoscopy for endoscopic
treatment. Previously, small-bowel DL were identified via angiography and treated
with either conservative management or surgical resection in cases of massive hemorrhage
[9 ]. However, since the initial case report in 1990 by Goldenberg et al. describing
the endoscopic characteristics and management of small bowel DL, questions regarding
a feasible alternative to surgical therapy have surfaced [10 ]. Limited data exists regarding enteroscopic treatment for these lesions with only
one Austrian experience where ten cases were treated with either a single or double-balloon
enteroscopy [11 ]. In this report we have reviewed our SBE data base to determine the outcomes for
patients that were treated for bleeding small-bowel DL since 2010.
Methods
Institutional Review Board approval was obtained from the University of South Florida
and Tampa General Hospital. Patients were selected from a database of patients that
underwent SBE from January 2010-August 2013 at Tampa General Hospital. Over this time
375 SBEs were performed for patients with suspected or documented small bowel bleeding
unreachable with either EGD or colonoscopic modalities. A total of 309 patients underwent
SBE with 348 performed anterograde, and 27 retrograde. Forty-two patients required
more than one SBE, either bidirectional or repeated in the same direction.
We collected information on demographics including: age, sex, comorbidities, smoking,
alcohol, and use of anticoagulation/antiplatelet agents or proton pump inhibitor therapy.
The diagnostic techniques used before SBE were also recorded including EGD, colonoscopy,
push enteroscopy, SBCE, and angiography. The hemodynamic status of each patient was
characterized by recording initial heart rate, blood pressure, hemoglobin, and number
of units of packed red blood cells transfused over the course of treatment ([Table 1 ]).
Table 1
Patient hemodynamic profiles.
Patient
Clinical presentation
Occult/Overt
Hemoglobin (g/dL)
Pressors
Transfusion (units)
Hospitalization (days)
1
Melena
Overt
7.4
No
14
27
2
Melena
Overt
N/A
No
N/A
2
3
Melena
Overt
5.5
No
7
6
4
Melena
Overt
6.0
No
10
7
5
Melena
Overt
9.3
No
7
6
6
Melena
Overt
7.0
No
1
7
7
Melena
Overt
8.7
No
3
3
8
Melena
Overt
5.3
No
4
4
Treatment
Diagnosis of DL was based on the finding of one of the three following criteria [11 ]:
A spurting artery or micropulsatile artery streaming from either a small mucosal defect
or normal surrounding mucosa;
Appearance of a fresh, adherent clot with a narrow point of attachment either to a
small mucosal defect or to normal surrounding mucosa; or
Visualization of a protruding vessel with or without active bleeding within either
a small mucosal defect or within normal mucosa.
The choice of hemostasis was left to the preference of the endoscopist. In our population:
Either multipolar Gold probe (Boston Scientific, Natick, Massachusetts, United States)
or argon plasma coagulation (Erbe Elektromedizin, Tübingen, Germany) was the primary
therapeutic modality. When these modalities failed a hemoclip application (Resolution
Clip; Boston Scientific, Natick, Massachusetts, United States) was performed.
Data were retrieved from a review of hospital medical records and by contacting patients
via telephone. Follow-up was defined as the time between enteroscopic hemostasis and
last patient contact, first rebleeding episode, or death.
Evaluation
Initial evaluation of all our patients for suspected obscure gastrointestinal bleeding
(OGIB) included both an initial EGD and colonoscopy as per current expert panel recommendations
[12 ]. OGIB is defined as “occult or overt bleeding that persists or recurs after an initial
negative endoscopic evaluation including colonoscopy and EGD”. Occult OGIB refers
to iron deficiency anemia or a positive fecal occult blood test when there is no evidence
of visible blood, whereas overt bleeding is categorized as bleeding from the gastrointestinal
tract that persist or recurs without an obvious etiology after EGD or colonoscopy.
SBCE was performed to assess the location of the lesion. Patients with a history of
inflammatory bowel disease or potential causes of small bowel obstruction were evaluated
with a patency capsule study before SBCE. The initial approach to SBE was determined
based on the combination of clinical symptoms (i. e. melena vs hematochezia), and
results of the SBCE where lesions found in the first 75 % of the small bowel were
approached anterograde. A retrograde approach was used in cases where lesions were
suspected in the distal 25 %. If no bleeding was detected on initial enteroscopy,
a submucosal tattoo was placed to mark the deepest insertion point, and the other
enteroscopic route was performed. In cases where bleeding continued, but no lesion
was detected on SBCE, an anterograde approach was used as the initial method of choice.
Entire small bowel enteroscopy was not performed if the suspected primary lesion was
found and hemostasis was achieved on the initial enteroscopic approach. In cases where
rebleeding was suspected, the initial diagnostic approach was repeated so repeat endoscopic
therapy could be performed when necessary. Interventional radiological embolization
or surgical intervention was planned only when endoscopic hemostasis could not be
achieved.
Single-balloon enteroscopy
Single-balloon enteroscopy (SBE) systems consists of a high-resolution endoscope (SIF-Q180;
Olympus Medical, Center Valley, Pennsylvania, United States) with a working length
of 200 cm, 9.2 mm in diameter, and contains a working channel of 2.8 mm diameter.
The disposable overtube (ST-SB1; Olympus Medical) was 140 cm long with a 13.2 mm outer
diameter, and was equipped with a latex-free balloon at the tip where air can be inflated
and deflated from a pressure-controlled pump system allowing for passage through the
small bowel [13 ]. For the anterograde approach, only an overnight fast was used, whereas bowel preparation
was used in cases of retrograde SBE. SBE was performed by one of four experienced
endoscopists. All eight cases where DL was identified were treated by a single endoscopist.
Sedation with propofol was used for all patients.
Statistical analysis
Descriptive statistics were employed to summarize the demographic data. The success
rate associated with use of SBE for bleeding DL was measured as the primary outcome.
Duration of follow-up was expressed as the mean follow-up time.
Results
Small bowel DLs were found in eight patients during the study period. Small bowel
DLs were found in an elderly population with an overall mean age of 71.5 years. One-half
of the patients were male and the predominant race was white (7/8 patients). Most
patients were on either anticoagulation or antiplatelet therapy with four patients
on at least two anticoagulant/antiplatelet agents (one was on both aspirin and Coumadin,
three on aspirin/Plavix), and 6/8 were on at least aspirin. Smoking was prevalent
in half, and alcohol use was listed in 2/8, however no patients used these agents
together. A history of peptic ulcer disease (PUD) or GERD was listed in 3/8 patients.
PPI therapy was used in four of the eight patients including two of the four who were
on at least two anticoagulant/antiplatelet agents together ([Table 2 ]).
Table 2
Demographic characteristics of patients undergoing single-balloon enteroscopy.
Case
Age (years)
Sex
Race
Comorbidities
Anticoagulant/Platelets
PPI
Smoking
Alcohol
1
86
Men
W
CABG, HTN, Afib with PPM, Bladder Cancer, Gastritis
ASA, Coumadin
Yes
Yes
No
2
73
Women
W
N/A
N/A
N/A
N/A
N/A
3
63
Men
W
MI, CABG, CHF, Afib, HTN, AS, CVA, OSA
ASA, Plavix
Yes
No
Yes
4
81
Men
W
CABG, CHF, PPM, Afib, HTN, AVR
ASA, Plavix
No
No
Yes
5
69
Women
W
GERD, PUD (non-bleeding), duodenal stenosis, benign colon polyps
ASA
Yes
Yes
No
6
60
Women
W
PUD, anemia, COPD
None
Yes
Yes
No
7
60
Women
Other (Trinidad)
MI, CHF, HTN, HLD, DM, Anemia
ASA
No
No
No
8
80
Men
W
MI, CHF, AS, MR/ TR, Afib, HTN, CVA
ASA, Plavix
No
Yes
No
Abbreviations: W, white; CABG, coronary artery bypass graft; HTN, hypertension; Afib, atrial fibrillation;
PPM, permanent pacemaker; ASA, aspirin; MI, myocardial infarction; CHF, congestive
heart failure; AS, aortic stenosis; CVA, cerebral vascular accident; OSA, obstructive
sleep apnea; AVR, aortic valve replacement; GERD, gastroesophageal reflux disease;
PUD, peptic ulcer disease; COPD, chronic obstructive pulmonary disease; HLD, hyperlipidemia;
DM, diabetes mellitus; MR, mitral regurgitation; TR, tricuspid regurgitation; N/A,
not available; PPI, proton pump inhibitor.
All patients experienced overt OGIB and reported melena on initial examination. All
patients underwent EGD, colonoscopy, and SBCE before SBE. One patient had push enteroscopy
before SBE and another had a prior angiogram with failed arterial embolization. The
mean time from the onset of symptoms until performance of SBCE was 60.6 days (range,
4 – 150; median, 30) and the mean time between SBCE and the diagnostic/therapeutic
SBE was 75.9 days (range, 12 – 210; median, 30). In all cases, the SBCE was performed
before the referral for SBE. There were no reports of angioectasia in any of the SBCE
studies. The initial mean hemoglobin found in the DL population was 7.0 gm/dL (range,
9.3 – 5.3). All patients required packed red blood cell transfusions with the average
use of 6.6 units (range, 3 – 14) required during hospitalization. All patients that
were found to have DL underwent anterograde SBE with 7/8 lesions found in the jejunum
and one found in the fourth portion of the duodenum. Active bleeding was observed
in 6/8 patients; two of the patients demonstrate oozing on initial diagnostic SBE
([Table 2 ] and [Table 3 ]).
Table 3
Patient diagnostic and outcome data.
Patient
Diagnostic modality
Location
DBE/
SBE
Approach
Enteroscopy (#)
Treatment (#)
Finding
AVM anywhere in gastrointestinal tract
Rebleed
1
E/C/SBCE/ IR
Jejunum
SBE
A
2
Bipolar/APC/Clip (1)
Active bleeding
No
No
2
E/C/SBCE
Jejunum
SBE
A
1
Bipolar
Spurting
No
No
3
E/C/SBCE
Jejunum
SBE
A
2
Bipolar/ Epi/ Clip (2)
Active bleeding
No
No
4
E/C/SBCE
Jejunum
SBE
A
1
Bipolar
Active bleeding
No
No
5
E/C/SBCE
4th portion duodenum
SBE
A
3
Bipolar/ Clip (1)
Oozing
No
No
6
E/C/ SBCE/ push enteroscopy
Jejunum
SBE
A
2
Bipolar/ Clip (4)
Oozing
No
Yes
7
E/C/SBCE
Jejunum
SBE
A
1
APC
Active bleeding
No
No
8
E/C/SBCE
Jejunum
SBE
A
2
Epi/Bipolar
Active bleeding
No
No
Abbreviations: DBE, double-balloon enteroscopy; SBE, single-balloon enteroscopy; AVM, arteriovenous
malformation; E, esophagogastroduodenoscopy; C, colonoscopy; SBCE, wireless small-bowel
capsule endoscopy; IR, interventional radiology embolization; A, anterograde; APC,
argon plasma coagulation; Epi, epinephrine injection.
The primary modality of therapy employed was electrocautery, multipolar electrocoagulation
in seven patients and APC in one ([Fig. 1 a, 1 b ] and [Fig. 2 a, 2 b ]). Epinephrine injection was used as an adjuvant therapy to initially slow bleeding
in two patients. In three patients, electrocoagulation was unsuccessful and hemostasis
was achieved with clip placement (resolution clips) ([Video 1 ] and [Video 2 ]). The average hospitalization for overt OGIB secondary to DL was 7.8 days (range,
2 – 27). The mean follow-up time for patients diagnosed with DL was 17.5 months (range,
1.5 – 44). Three patients required repeat SBE with one found to have rebleeding from
a failed clip. Two patients requiring repeat SBE were treated initially with bipolar/clip
(one patient treated with four clips and the second with one clip), and the third
patient initially treated with epinephrine/bipolar therapy. The patient treated with
four clips was found to have rebleeding occurring two weeks after the initial SBE
and achieved hemostasis with reapplication of one clip. Repeat SBE was performed at
two months and four months in patient five, however no rebleeding was noted at the
tattooed area where the previous DL was identified. Patient number 8 had noted rebleeding
44 months post initial anterograde SBE; a subsequent anterograde SBE was negative
for bleeding, and bleeding resolved with conservative management ([Table 3 ] and [Table 4 ]).
Fig. 1 a Active bleeding from mid jejunal Dieulafoy lesion. b Cessation of bleeding post therapy.
Fig 2 a Active bleeding from jejunal Dieulafoy lesion after initial argon plasma coagulation.
b Cessation of bleeding after final argon plasma coagulation therapy.
Dieulafoy lesion (DL) identified during single-balloon enteroscopy in the mid jejunum.
Initially, the lesion was actively bleeding with a steady stream of blood in the absence
of an identifiable mucosal ulceration or angioectasia. After identification, the lesion
was treated successfully using multipolar electrocauterization.
Dieulafoy lesion (DL) identified during single-balloon enteroscopy in the jejunum.
Initially, the lesion was oozing with an adherent clot. After initial treatment with
argon plasma coagulation therapy the lesion began to bleed actively, but with further
treatment bleeding ceased.
Table 4
Patient follow-up information.
Patient
Repeat enteroscopy/rebleed
Time to rebleed (days)
Time since last treatment (months)
1
No repeat
-
12
2
No repeat
-
19
3
No repeat
-
18
4
No repeat
-
8
5
2 months & 4 months (No active bleeding found at tattooed area)
-
7
6
Repeat (Failed clip, re-applied)
12
46*
7
No repeat
-
15
8
44 months (No active bleeding found)
-
44
Note: *, days
Discussion
DL lesions are now a well-recognized etiology of upper gastrointestinal bleeding with
frequencies ranging from 0.5 % to 14 % [14 ]
[15 ]
[16 ]
[17 ]. DL may be found throughout the gastrointestinal tract from esophagus to the colon
[9 ]
[18 ]
[19 ], however, their distribution is uneven. Most occur in the stomach with (61 % to
82 %) found in the proximal one-third, and up to 98 % found in the upper stomach,
predominantly on the lesser curvature [20 ]
[21 ]. Small-bowel DL first appeared in the literature in 1978 with two patients treated
surgically for jejunal lesions [9 ]. However, cases with similar histology reported as “aneurysms” of the small bowel
have been reported since 1944 [7 ]. In one systematic review, the mean percentage of DL located in the small bowel
was 16 % (duodenum, 15 %; jejunum-ileum, 1 %). The incidence of small-bowel DL as
a cause of OGIB is sparsely reported ([Table 5 ]) [11 ]
[22 ]
[23 ]
[24 ]
[25 ]
[26 ]. In patients undergoing BAE, the incidence of small-bowel DL is reported to range
from 2.6 % to 7.2 % [11 ]
[22 ]
[23 ]
[24 ]. Our incidence of 2.6 % is similar to the current literature, however, these may
be vast underestimates as misidentified, non-bleeding DL, or those not reachable with
BAE may lead to an underdiagnoses. The small mucosal defect often present and intermittent
bleeding nature found in some DL may also contribute to underdiagnoses, or explain
at least a portion of idiopathic cases of OGIB after negative BAE. One retrospective
review of patients undergoing evaluation for OGIB found an incidence of 1.32 % (3/227)
small-bowel DL in patients undergoing SBCE that were later diagnosed on BAE [27 ]. Similar to our experience, the predominant location of small-bowel DL in several
case series or retrospective reviews with BAE appears to be the jejunum (range 80 %
to 100 %) [11 ]
[23 ]
[24 ]
[25 ].
Table 5
Incidence of small-bowel Dieulafoy lesion and obscure gastrointestinal bleeding.
Study
DL (#)
Capsule positive
Incidence (%)
Anterograde
Duodenum (#)
Jejunum (#)
Ileum (#)
SBE (#)
DBE (#)
> 2 enteroscopy sessions before diagnosis
Rebleeds (#)
Follow-up (months)
Dulic-Lakovic et al, 2011 [11 ]
10
N/A
3.5
9/10
0
9
1
3
7
4
2 DBE, 1 SBE
Median, 14.5
Landaeta, et al, 2013 [22 ]
17
N/A
7.2
12/17
N/A
N/A
N/a
N/A
N/A
4
1
Median, 9
Chen et al, 2010 [23 ]
4
N/A
2.6
4/4
0
4
0
0
4
0
1
Mean, 8.8
Prachayakul et al, 2013 [24 ]
5
N/A
4.31
5/5
0
5
0
5
0
N/A
0
N/A
Paliwal et al, 2011 [25 ]
5
3/4
N/A
N/A
0
4
1
5
0
0
1
4 – 12
Abbreviations: DL, Dieulafoy lesion; N/A, data not available or missing; N/P, not performed; DBE,
double-balloon enteroscopy; SBE, single-balloon enteroscopy.
Endoscopic management for general DL includes: banding, clipping, electrocautery,
cyanoacrylate glue, sclerosant injection, epinephrine injection, heater probe, and
laser therapy [28 ]. Epinephrine injection monotherapy is associated with higher rates of recurrent
rebleeding [16 ], but may be useful in combination to slow bleeding and optimize visualization of
the lumen for thermal/mechanical therapy. Studies have shown that mechanical endoscopic
methods such as hemoclip and band ligation are more effective than injection and thermal
therapy for general DL located predominantly in the stomach [29 ]
[30 ]
[31 ]
[32 ]
[33 ]. The optimal treatment approach for small-bowel DL has not been reported in any
large scale study. Based on our experience, mechanical clipping may be the therapy
of choice since it was successful in three cases where thermal methods failed, and
in patient one where a prior interventional radiological embolization failed to stop
bleeding.
Bleeding from small-bowel DL may be life threatening [34 ]
[35 ], and before 1990 was treated surgically. Goldenberg first reported a case of bleeding
duodenal DL successfully treated with epinephrine injection therapy and electrocoagulation
[10 ]. Sporadic case reports and case series have since surfaced reporting success with
BAE [11 ]
[22 ]
[23 ]
[24 ]
[25 ]
[26 ]. In our population, either bipolar or APC therapy was used as initial therapy of
choice. When these modalities failed a hemoclip was placed. This approach provided
initial hemostasis in all eight patients. Initial hemostasis without rebleeding was
87.5 % (7/8) in our series using SBE as our primary therapeutic modality and eventually
reached 100 % without any patients proceeding to surgery. Dulic-Lakovic et al reported
rebleeding in 3/10 patients undergoing BAE (2/7 DBE, 1/3 SBE) with 2/10 patients eventually
requiring surgical intervention [11 ].
Chronic intermittent bleeding maybe encountered when treating small-bowel DL resulting
in multiple BAEs before diagnosis. Dulic-Lakovic et al. reported 4/10 requiring at
least two or more BAEs before diagnosis [11 ]. The diagnostic yield in patients undergoing first look endoscopy varies in gastric
DL with reports ranging from 63 % to 92 % [2 ]
[36 ]
[37 ]. From our experience with small-bowel DL all patients were diagnosed on initial
SBE. The usefulness of repeating BAE after an initial negative BAE should be determined
based on index of suspicion, previous diagnostic testing results, and the hemodynamic
profile of each individualized patient.
The profile of our patients diagnosed with small-bowel DL included a group that was
predominantly elderly (mean age, 71.5 years), and had multiple cardiac comorbidities
5/8 (62.5 %). A few case series of small-bowel DL treated with BAE reported a similar
experience where mean ages of 69.7 and 77 years were reported although data on cardiovascular
risk factors and anticoagulation/antiplatelet/NSAID use were unavailable [11 ]
[23 ]
[38 ]. Small-bowel DL does exist in younger patients. A study of 17 patients, median age
54 years (range, 15 – 80), reported a 15 year old treated for a small-bowel DL [22 ]. Cardiac comorbidities and use of antiplatelet/coagulation/NSAID have not been studied
as a risk factor for small-bowel DL. Gastric DL studies have reported the prevalence
of cardiovascular disease, diabetes, or chronic renal disease as high as 90 % in patients
found to have bleeding gastric DL [28 ]. Likewise the use of medications affecting coagulation has ranged from 28 % to 51 %
of cases identified as gastric DL [16 ]
[28 ]
[36 ]
[39 ]. Whether our high incidence of cardiac comorbidities occurred by chance, and whether
the NSAID/antiplatelet use is related to an elderly population at risk for cardiac
comorbidities/arthritis remains to be determined with larger studies.
Limitations of our experience include the small cohort of patients diagnosed with
DL and the retrospective study design. However, our experience adds to the very limited
data on small-bowel DL found in the literature, and is the first US reported experience
with an extended follow-up. We also have reported a more descriptive patient profile,
and have demonstrated that SBE has been an effective treatment modality in patients
found to have DL (100 % success) in addition to reviewing the current literature on
this topic.
Conclusion
Misidentified, intermittent non-bleeding DL, or those not reachable with BAE may lead
to an underdiagnoses and may explain at least a portion of idiopathic cases of OGIB.
Therefore, we recommend an early aggressive approach with BAE after initial negative
colonoscopy/EGD, or in cases where a high index of suspicion exists to ensure identification
and treatment. The usefulness of repeating BAE after initial negative BAE should be
determined based on clinical suspicion, previous diagnostic testing results, and the
hemodynamic profile of each patient. In our U.S. experience, SBE offers a reasonable
therapeutic approach to treat DL of the small bowel with a low rates of rebleeding,
no adverse events, and no patient going on to require surgery.
