Introduction
Colonic diverticular hemorrhage is the most common cause of acute lower gastrointestinal
bleeding (LGIB), and therapeutic intervention is needed in severe bleeding cases [1]
[2]
[3]
[4]
[5]. Several types of endoscopic treatments such as coagulation therapy, epinephrine
injection, and endoscopic clipping have been performed to achieve hemostasis of colonic
diverticular hemorrhage [6]
[7]
[8]
[9]
[10]
[11].
Endoscopic variceal ligation (EVL) is widely used as a treatment for esophageal variceal
bleeding. Recently, endoscopic band ligation (EBL), which uses devices and techniques
similar to those for EVL, has been used for hemostasis of colonic diverticular hemorrhage
and has been reported as a safe and effective endoscopic treatment for that indication
[12]
[13]
[14]
[15]
[16]
[17]
[18]. However, rebleeding after EBL was reported in some cases, and the risk factors
for it remain to be identified [16]
[17].
The aim of this retrospective study was to elucidate the risk factors for early rebleeding
after EBL following treatment of colonic diverticular hemorrhage.
Patients and methods
Study population
Endoscopy records for patients with acute LGIB treated at St. Luke’s International
Hospital in Tokyo from June 2009 to October 2014 were retrospectively reviewed.
During that period, 108 patients with definite diverticular hemorrhage with stigmata
of recent hemorrhage (SRH) [active bleeding (AB), non-bleeding visible vessel (NBVV),
or adherent clot (AC)] [6] were treated. Patients treated with transcatheter arterial embolization (TAE), epinephrine
injection, or endoscopic clipping as a first-line therapy were excluded, and a total
of 101 patients with definite diverticular hemorrhage successfully treated using EBL
were ultimately included in the retrospective cohort study.
EBL methods and repeat colonoscopy for rebleeding
The method of EBL for colonic diverticular hemorrhage was the same as that reported
in the previous literature [14]
[15]
[16]
[17]. Well-trained endoscopists and a trainee supervised by the experts performed EBL
in the current study. After fluid resuscitation, bowel purge was done with polyethylene
glycol and colonoscopy was performed. When the diverticulum with SRH was detected,
the area was marked with ([Fig. 1 a] and 1 b). Epinephrine injection was not performed for the diverticula with AB before EBL.
The colonoscope was removed, the band-ligator device was attached to the tip, and
the colonoscope was reinserted. The diverticulum was sucked into the band-ligator
and the O-band was released ([Fig. 1 c]).
Fig. 1 a Endoscopic view of the colonic diverticulum with active bleeding. b Marking with the hemoclips was done near the diverticulum. c The colonoscope was pulled off and reinserted after attachment of the band ligator.
The elastic O-band was released and successful hemostasis was obtained.
Patients consumed a liquid meal the day after EBL and were usually discharged a few
days after the procedure. Antiplatelet agents or nonsteroidal anti-inflammatory drugs
(NSAIDs) were reintroduced the day after EBL, if required. Patients were basically
followed on an outpatient basis at St. Luke’s International Hospital for at least
30 days after EBL. In patients who had been taking regular meals and experienced rebleeding,
a bowel purge with polyethylene glycol was done and repeat colonoscopy was performed
using a water-jet scope (PCF-Q260AZI, PCF-Q260JI, or GIF-Q260J; Olympus Medical Systems)
to rule out other bleeding sources. In some patients, repeat colonoscopy was performed
without a bowel purge. The same gastroenterologists or on-call gastroenterologists
performed the repeat colonoscopy. Further treatments were administered based on the
judgments of the attending gastroenterologists. Patients who were not followed up
at St. Luke’s International Hospital were contacted by telephone. This study was approved
by the ethics committee of St. Luke’s International Hospital, and written informed
consent was obtained from all patients.
Comparison between rebleeding and non-rebleeding groups
The 101 enrolled patients were divided into rebleeding and non-rebleeding groups based
on the presence or absence of early rebleeding, which was defined as rebleeding within
30 days after initial treatment [6]. Comorbid diseases (hypertension, hyperlipidemia, and diabetes mellitus), use of
antiplatelet agents or NSAIDs, SRH (AB vs. NBVV and AC), location of bleeding diverticula
[right colon (cecum, ascending colon, and transverse colon) vs. left colon (descending
colon and sigmoid colon)], and the eversion of the diverticula after EBL were retrospectively
evaluated in each group.
Statistical analysis
Statistical analysis was performed using JMP version 9 (SAS Institute Inc., USA).
The patients’ ages were reported as mean [standard deviation (SD)]. Student’s t-test
and Fisher’s exact test were applied for continuous and categorical variables, respectively,
and a P value less than 0.05 was considered statistically significant. Odds ratios (ORs) and
their 95 % confidence intervals (CI) were calculated by multiple logistic regression
analysis.
Results
Characteristics of rebleeding cases after EBL
The characteristics of 15 early rebleeding patients are listed in [Table 1]. Early rebleeding occurred in 15 % of the patients (cecum, n = 4; ascending colon,
n = 3; transverse colon, n = 1; descending colon, n = 1; sigmoid colon, n = 6). The
median time (range) of early rebleeding occurrence was 5 days (range, 2 h to 26 days).
Table 1
Characteristics of 15 early rebleeding cases after EBL.
|
No.
|
Age
|
Gender
|
Location
|
Eversion
after
initial EBL
|
Time to
rebleeding
after EBL
(hours or days)
|
Time to
repeat endoscopy
(hours or days)
|
Endoscopic feature
at the initial EBL sites
|
Additional
treatments
|
|
1
|
69
|
M
|
S
|
(–)
|
2
|
20
|
Dislodgement of O-ring
|
Repeat EBL
|
|
2
|
75
|
M
|
S
|
(–)
|
11
|
17
|
Dislodgement of O-ring
|
Repeat EBL
|
|
3
|
46
|
M
|
A
|
(+)
|
10
|
56
|
Ulcer with visible vessel
|
Clip
|
|
4
|
34
|
M
|
C
|
(+)
|
44
|
53
|
Ulcer with visible vessel
|
Clip
|
|
5
|
67
|
M
|
C
|
(–)
|
66
|
75
|
Ulcer without visible vessel
|
Conservative management
|
|
6
|
93
|
M
|
S
|
(+)
|
12 days
|
12 days
|
Ulcer without visible vessel
|
Conservative management
|
|
7
|
37
|
M
|
A
|
(+)
|
13
|
17
|
Yellowish tissue
|
Surgery
|
|
8
|
70
|
M
|
A
|
(+)
|
22
|
24
|
Yellowish tissue
|
Conservative management
|
|
9
|
77
|
M
|
T
|
(+)
|
32
|
35
|
Black tissue
|
Conservative management
|
|
10
|
46
|
M
|
C
|
(+)
|
33
|
49
|
Yellowish tissue
|
Conservative management
|
|
11
|
66
|
F
|
S
|
(+)
|
90
|
99
|
Yellowish tissue
|
Conservative management
|
|
12
|
55
|
M
|
C/A[1]
|
(+)
|
11
|
20
|
Black tissue
(Bleeding from other diverticulum)
|
EBL
|
|
13
|
78
|
F
|
D/S[2]
|
(+)
|
21 days
|
24 days
|
Ulcer with no vessel
(Bleeding from other diverticulum)
|
EBL
|
|
14
|
55
|
M
|
S
|
(+)
|
26 days
|
27 days
|
Scar formation
(Bleeding from other diverticulum)
|
Conservative management
|
|
15
|
94
|
F
|
S
|
(+)
|
60
|
(-)
|
No repeat endoscopy
|
Conservative management
|
C, cecum; A, ascending colon; T, transverse colon; D, Descending colon; S, sigmoid
colon
1 Initial bleeding sites and early rebleeding site were cecum and ascending, respectively.
2 Initial bleeding sites and early rebleeding site were descending and sigmoid, respectively.
In two cases (cases 1 and 2) where rebleeding occurred at 2 h and 11 h after initial
EBL, dislodgement of the O-band was observed in repeat colonoscopy, and EBL was repeated
([Fig. 2]). Complete eversion of the banded diverticula had not been achieved during the first
EBL sessions in either case.
Fig. 2 a Early rebleeding was observed from the previously banded diverticulum, owing to early
dislodgement of the O-band (case 1). b Repeat EBL was performed and bleeding stopped.
Ulceration was observed at the banded site in repeat colonoscopy in four early rebleeding
cases. Two of those patients (cases 3 and 4) underwent endoscopic clipping at the
visible vessel on the ulcer base ([Fig. 3]). No interventions were required in the other two patients (cases 5 and 6), owing
to the absence of visible vessels.
Fig. 3 a A non-bleeding visible vessel was observed at the post-EBL ulcer (case 4). b Endoscopic clipping was performed.
The banded diverticula transformed into yellowish or black balls on repeat colonoscopy
performed in five early rebleeding cases (cases 7 – 11) ([Fig. 4]), which had no other demonstrable bleeding sources. Eversion of the diverticula
after EBL had been observed during the first EBL in five cases. In one of these five
cases (case 7), right hemicolectomy was performed as the patient’s preference, whereas
the other four cases were managed conservatively without any interventions.
Fig. 4 The banded diverticulum became yellowish on repeat colonoscopy (case 11).
In twoearly rebleeding cases (cases 13 and 14), repeat colonoscopy 11 h and 24 days
after the initial EBL demonstrated active bleeding from the diverticula that differed
from the bleeding seen previously, and EBL was repeated. Hemostasis was obtained,
and rebleeding did not occur during the follow-up periods of 59 and 37 months, respectively.
In case 15, repeat colonoscopy showed scar formation at the previously banded site.
However, the rebleeding source was not identified. In case 16, repeat colonoscopy
was not performed, owing to severe cardiopulmonary diseases, and rebleeding was managed
conservatively.
Comparison between rebleeding and non-rebleeding groups
A comparison between 15 rebleeding and 86 non-rebleeding cases is presented in [Table 2]. No significant differences were noted for the parameters. However, left-sided location
and AB of SRH were more common in the rebleeding group than in the non-rebleeding
group, and these differences were considered marginally significant (P = 0.05 and P = 0.08, respectively).
Table 2
Characteristics of rebleeding and non-rebleeding groups.
|
Rebleeding group (n = 15)
|
Non-rebleeding group (n = 86)
|
P value
|
|
Male gender, n (%)
|
11 (73)
|
63 (73)
|
1.00
|
|
Age, mean ± SD (years)
|
63 ± 17
|
65 ± 13
|
0.46
|
|
History of HT, n (%)
|
8 (53)
|
46 (53)
|
1.00
|
|
History of DM, n (%)
|
2 (13)
|
11 (13)
|
1.00
|
|
History of HL, n (%)
|
6 (40)
|
18 (20)
|
0.18
|
|
Antiplatelet agents or NSAIDs, n (%)
|
5 (33)
|
34 (39)
|
0.77
|
|
Location in colon (C/A/T/D/S)
|
4/3/1/1/6
|
3/57/8/7/11
|
|
|
Right side (C/A/T), n (%)
|
8 (53 %)
|
68 (79 %)
|
0.05
|
|
SRH:AB, n (%)
|
9 (60)
|
29 (33)
|
0.08
|
|
Complete eversion, n (%)
|
11 (73)
|
76 (88)
|
0.22
|
HT, hypertension; DM, diabetes mellitus; HL, hyperlipidemia; NSAIDs, nonsteroidal
anti-inflammatory drugs; C, cecum; A, ascending colon; T, transverse colon; D, descending
colon; S, sigmoid colon; SRH, stigmata of recent hemorrhage; AB, active bleeding.
Statistical significance was defined as P < 0.05.
[Table 3] presents results of multivariate analysis of the risk factors of early rebleeding
after EBL. This analysis revealed that age younger than 50 (adjusted OR, 8.7; 95 %
CI 1.6 – 52.5; P = 0.014) and AB (adjusted OR, 4.21; 95 % CI 1.15 – 18.1; P = 0.03) were significant risk factors. The right side of the colon carried lesser
risk than did the left side (adjusted OR, 0.21; 95 % CI0.04 – 0.84; P = 0.028).
Table 3
Multivariate analysis of risk factors of early rebleeding after EBL.
|
Crude OR
(95 % CI)
|
P value
|
Adjusted OR (95 %CI)
|
P value
|
|
Age under 50
|
3.11
(0.74 – 11.5)
|
0.11
|
8.7
(1.6 – 52.5)
|
0.014
|
|
Male gender
|
1.00
(0.3 – 3.9)
|
1.00
|
|
|
|
History of HT
|
0.99
(0.33 – 3.01)
|
1.00
|
|
|
|
History of DM
|
1.05
(0.15 – 4.52)
|
0.95
|
|
|
|
History of HL
|
2.51
(0.76 – 7.95)
|
0.13
|
2.97
(0.78 – 11.4)
|
0.11
|
|
Antiplatelet agents or NSAIDs
|
0.76
(0.22 – 2.35)
|
0.67
|
|
|
|
Right side
(C/A/T)
|
0.30
(0.1 – 0.97)
|
0.04
|
0.21
(0.04 – 0.84)
|
0.028
|
|
SRH:AB
|
2.94
(1.38 – 18.7)
|
0.05
|
4.21
(1.15 – 18.1)
|
0.03
|
|
Complete eversion
|
0.36
(0.10 – 1.49)
|
0.15
|
0.34
(0.07 – 1.74)
|
0.19
|
HT, hypertension; DM, diabetes mellitus; HL, hyperlipidemia; NSAIDs, nonsteroidal
anti-inflammatory drugs; C, cecum; A, ascending colon; T, transverse colon; D, descending
colon; S, sigmoid colon; SRH, stigmata of recent hemorrhage; AB, active bleeding;
Statistical significance was defined as P < 0.05; OR, odds ratio; CI, confidence intervals.
Discussion
The aim of this retrospective cohort study of EBL for colonic diverticular hemorrhage
was to determine the risk factors for rebleeding after EBL. In the current study,
repeat colonoscopy was performed for early rebleeding after EBL, and further treatments
for early rebleeding were selected according to the endoscopic features of post-EBL
sites as follows: repeat EBL for early dislodgement of the O-band, endoscopic clipping
for visible vessels at the post-EBL ulcer, no intervention in ulcer cases with no
visible vessels or in the cases of yellow or black tissues, and EBL for different
bleeding diverticula. Importantly, the yellowish or black tissues are considered necrotic
tissues after EBL and should not be removed because the muscularis propria may be
banded by the O-band and the yellowish or black tissues can contain muscularis propria
[17]. Given the results, which indicate that early rebleeding can be managed conservatively
and/or by endoscopic treatment (except in one ascending case), repeat colonoscopy
can be considered useful for determining information about the banded sites after
EBL and for selecting further endoscopic procedures that would obviate the need for
more invasive treatments such as surgery.
On repeat colonoscopy, another lesion was identified as the source of bleeding in
cases 13 and 14, which might lead to the conclusion that EBL was performed mistakenly
on the first lesions targeted. That was not the case, however, because SRH were evident
in the diverticula initially treated with EBL. In addition, in this study, early rebleeding
was defined as rebleeding within 30 days after initial EBL. Therefore, cases 13 and
14 were not excluded from the analysis.
The vascular anatomy at the diverticulum consists of arcades of arteries from the
neck that join and form the artery in the base of the diverticulum, and bleeding from
the ruptured vasa recta occurs in colonic diverticular hemorrhage [19]. Although the diameter of the vessel at the diverticula and the extent of significant
hemorrhage could not be assessed in this study, these factors may contribute to early
rebleeding after EBL, given that AB was a significant risk factor for early rebleeding.
Colonic diverticulosis and diverticular bleeding are more common in the right colon
of patients from eastern countries including Japan, and a location in the right colon
–, especially the ascending colon – was reported as a predictor of refractory colonic
diverticular hemorrhage after endoscopic clipping [11]. However, left-sided location was a significant risk factor for early rebleeding
after EBL in this study. Ex-vivo study of EBL of the colon using a fresh surgical
specimen revealed inclusion by the band ligator of the muscularis propria in the right
colon and the submucosa in the left colon [20]., The surgical specimen from the banded diverticulum in the ascending colon also
contained the muscularis propria [17]. Given these results, inclusion of the muscularis propria in the O-band may be necessary
to prevent early rebleeding when using EBL to treat colonic diverticular hemorrhage.
Therefore, a diverticular location in the left colon should be considered as a risk
factor specific to EBL rather than an overall risk factor for diverticular rebleeding.
Non-eversion of the diverticula after EBL, on the other hand, was not a risk factor
for early rebleeding after EBL. As a consequence, EBL may be useful for treatment
of stigmata regardless of eversion of the banded diverticular, if reliable banding
is obtained and EBL can occlude either the major SRH or the underlying artery.
Hypertension, arteriosclerosis, and regular use of anti-platelet agents or NSAIDs
have been reported to be risk factors for colonic diverticular hemorrhage [21]
[22]
[23]
[24]. In general, younger patients are considered to have fewer comorbidities, but in
this study, younger age was a risk factor for early rebleeding after EBL. The reason
for this association could not be identified, and further studies are necessary to
clarify the relationship of age to risk of rebleeding after EBL.
The rebleeding from the diverticula seen in this study differed from outcomes with
previously banded diverticula in three rebleeding cases, and in some rebleeding cases,
bleeding sources other than the banded site were not identified with certainty in
repeat colonoscopy. Specifically, the three cases reported here may not be “early
rebleeding cases,” as the latter cases were. However, the sources of early rebleeding
after endoscopic treatments were considered to be from the same diverticula treated
endoscopically, although that was not fully established.
Establishing risk factors for recurrent bleeding after EBL may not change the treatment
strategy and another endoscopic treatment or surgery may be desirable in patients
who have risk factors. With the exception of one case in which surgery was performed
because of patient preference, neither surgery nor TAE was not needed to control early
rebleeding because management was possible with conservative therapy and/or endoscopic
clipping in this study. Previously banded diverticula also may resolve after EBL,
preventing late rebleeding from the same diverticula [17]. Therefore, if there are no particular concerns, EBL is considered the first priority.
It may be useful to identify risk factors for early rebleeding after EBL so that patients
with colonic diverticular hemorrhage who those risk factors can be closely followed.
In conclusion, although the number of patients was limited and the study design was
retrospective, younger age, AB of SRH, and left-sided lesions were identified as the
risk factors of early rebleeding after EBL in the treatment of colonic diverticular
hemorrhage.
