Clinical outcomes of patients who experienced perforation associated with endoscopic retrograde cholangiopancreatography.

Abstract

Perforation after endoscopic retrograde cholangiopancreatography (ERCP) is a rare but severe complication. The purpose of this study was to assess the clinical outcomes with perforations after ERCP from a large number of cases.
Among 11,048 patients who underwent ERCP during 10 years, medical records from 68 patients (0.62 %) who experienced post-ERCP perforation with radiologic, endoscopic, or surgical evidence were retrospectively reviewed. We assessed the clinical outcomes of patients and analyzed the factors associated with poor outcomes, which were defined as mortality, prolonged hospital stay due to complications, or loss of chance of cure in the case of cancer.
Twenty-nine patients were male, and the median age was 65.0 years. Therapeutic ERCP was performed in 52 cases (77 %). Common mechanisms of perforation were endoscopic sphincterotomy (37 %), catheter or guidewire (34 %), and endoscope (19 %). In contrast to 9 patients who underwent emergent operation, 59 patients (87 %) were conservatively treated. In 44 patients, perforation was detected during the procedure; however, detection after 24 h or permitted oral intake before detection occurred in 18 cases (27 %). Although 58 patients recovered without poor outcomes, 10 patients (15 %) experienced poor outcomes, which consisted of mortality (n = 4), loss of chance of cure (n = 2), and prolonged hospital stay without surgery more than 1 month due to complications (n = 4). By multiple logistic regression analysis, perforation by endoscope and rebound tenderness was statistically associated with poor outcomes (odds ratio: 13.7 and 7.3, respectively).
Most patients fully recovered from perforation; however, some patients experienced grave outcomes, including mortality. Perforation by endoscope and rebound tenderness was significantly associated with poor outcomes.

Full text

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Clinical outcomes of patients who experienced perforation
associated with endoscopic retrograde cholangiopancreatography
Jaihwan Kim•Sang Hyub Lee•Woo Hyun Paik•
Byeong Jun Song•Jin Hyeok Hwang•
Ji Kon Ryu•Yong-Tae Kim•Yong Bum Yoon
Received: 19 January 2012/Accepted: 24 April 2012/Published online: 31 May 2012
? Springer Science+Business Media, LLC 2012
Abstract
Background
cholangiopancreatography (ERCP) is a rare but severe
complication. The purpose of this study was to assess the
clinical outcomes with perforations after ERCP from a
large number of cases.
Methods
Among 11,048 patients who underwent ERCP
during 10 years, medical records from 68 patients (0.62 %)
who experienced post-ERCP perforation with radiologic,
Perforation afterendoscopicretrograde
endoscopic, or surgical evidence were retrospectively
reviewed. We assessed the clinical outcomes of patients and
analyzed the factors associated with poor outcomes, which
were defined as mortality, prolonged hospital stay due to
complications,orlossofchanceofcureinthecaseofcancer.
Results
Twenty-nine patients were male, and the median
age was 65.0 years. Therapeutic ERCP was performed in
52 cases (77 %). Common mechanisms of perforation were
endoscopic sphincterotomy (37 %), catheter or guidewire
(34 %), and endoscope (19 %). In contrast to 9 patients who
underwent emergent operation, 59 patients (87 %) were
conservatively treated. In 44 patients, perforation was
detectedduringtheprocedure;however,detectionafter24 h
orpermittedoralintakebeforedetectionoccurredin18cases
(27 %). Although 58 patients recovered without poor out-
comes, 10 patients (15 %) experienced poor outcomes,
which consisted of mortality (n = 4), loss of chance of cure
(n = 2), and prolonged hospital stay without surgery more
than 1 month due to complications (n = 4). By multiple
logistic regression analysis, perforation by endoscope and
rebound tenderness was statistically associated with poor
outcomes (odds ratio: 13.7 and 7.3, respectively).
Conclusions
Most patients fully recovered from perfora-
tion; however, some patients experienced grave outcomes,
including mortality. Perforation by endoscope and rebound
tenderness was significantly associated with poor outcomes.
Keywords
cholangiopancreatography ? Complications ?
Perforation ? Prognosis
Endoscopic retrograde
Even after the introduction of less invasive modalities,
such as magnetic resonance cholangiopancreatography
or endoscopic ultrasonography, endoscopic retrograde
J. Kim ? S. H. Lee ? W. H. Paik ? B. J. Song ?
J. H. Hwang ? J. K. Ryu ? Y.-T. Kim ? Y. B. Yoon
Department of Internal Medicine and Liver Research Institute,
Seoul National University College of Medicine, Seoul, Korea
e-mail: drjaihwan@gmail.com
W. H. Paik
e-mail: iatrus@hanmail.net
B. J. Song
e-mail: directxxx@naver.com
J. H. Hwang
e-mail: woltong@dreamwiz.com
J. K. Ryu
e-mail: jkr1965@medimail.com
Y.-T. Kim
e-mail: yongtkim@snu.ac.kr
Y. B. Yoon
e-mail: yyb10604@plaza.snu.ac.kr
J. Kim
Department of Internal Medicine, Kangwon National University
School of Medicine, Chuncheon, Korea
S. H. Lee (&) ? J. H. Hwang
Department of Internal Medicine, Seoul National University
Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam,
Gyeonggi-do 463-707, South Korea
e-mail: gidoctor@snubh.org
123
Surg Endosc (2012) 26:3293–3300
DOI 10.1007/s00464-012-2343-z
and Other Interventional Techniques

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cholangiopancreatography (ERCP) has an important role as
a useful interventional endoscopic method in the pancre-
aticobiliary system. However, complications after ERCP
are inevitable due to the essential characteristics of the
technique, and the rates of complications are known to be
4–16 % [5, 6]. In particular, perforation after ERCP, which
is a rare but serious complication, occurs in less than
0.1–1.1 % of patients [5, 6, 10].
In contrast to surgical repair, which is the traditional
approach [3], selective approaches to perforation associ-
ated with ERCP have been proposed in a few reports [1, 8,
11, 12, 14]. Based on these studies, there were some
guidelines about decisions regarding conservative versus
surgical management. Although perforation continues to
be, without a doubt, the most serious complication, many
patients have recovered from it without any serious inci-
dents due to such guidelines in addition to advances in
supportive management or surgical technique. However,
some patients experienced serious clinical outcomes, and
there are still many unknown factors associated with out-
come, regardless of surgery [1]. Therefore, assessment of
clinical course and management methods also should be
made. This study was designed to assess the clinical out-
comes of patients who experienced perforation after ERCP
and analyze what kind of clinical factors were associated
with them.
Materials and methods
Study population
A total of 8,613 ERCPs were performed at Seoul
National University Hospital from June 2001 to May
2011, and a total of 2,435 ERCPs were done at Seoul
National University Bundang
2003 to May 2011. Among these, we tried to find ERCP-
related perforation cases that had supporting evidence
with reports from radiology, endoscopy, or surgery.
Radiologic evidence was defined as pneumoperitoneum
or pneumoretroperitoneum on chest radiograph, abdomen
radiograph, or computed tomography (CT) in addition
to dye leakage or abnormal air on fluoroscopy during
ERCP. Endoscopic evidence was defined as identified
abdominal cavity via a perforated lumen by endoscope.
Surgical evidence was defined as confirmed perforation
by surgery and pathology (Fig. 1). We excluded sus-
pected cases without definite evidence in this study.
According to the above-mentioned definition, a total of
68 cases (0.62 %, 54 cases at Seoul National University
Hospital and 14 cases at Seoul National University
Bundang Hospital) of ERCP-related perforation were
identified in both hospitals.
HospitalfromMarch
ERCP and procedures
Intravenous midazolam was used for conscious sedation of
patients (3–5 mg with slow intravenous injection with
titration). All ERCP procedures were performed with
fluoroscopic assistance. The endoscopes used were JF-200,
JF-240, TJF-200, or TJF-240 (Olympus Optical Co. Ltd,
Tokyo, Japan). According to the purpose of ERCP as
diagnostic or therapeutic, diagnostic procedures in this
study included acquisition of a cholangiogram or pan-
creatogram, brush cytology, or forceps biopsy, and thera-
peutic procedures included endoscopic sphincterotomy,
stent insertion, stone removal, or endoscopic papillectomy.
Some patients underwent ERCP for both purposes. After
ERCP, the supine abdomen X-ray or simple chest X-ray for
detection of perforation was routinely performed.
Definition of events and clinical outcomes
Inthisstudy,anurgentcasemeantthatthepatientreceivedthe
procedure mainly because of cholangitis in the emergency
room.Adelayeddetectioninthisstudymeantidentificationof
perforationafter oralintakeoffoodorafter morethan12 hin
thecaseofnooralintake.Meanwhile,wedividedpatientsinto
twogroupsofgoodandpoorclinicaloutcomes. A group with
poorclinicaloutcomeswasdefinedasanaggregateofpatients
who died due to perforation, experienced prolonged hospital
stay without surgery for more than 1 month due to compli-
cations, or lost the chance of cure in the case of cancer. A
group with good outcomes was defined as an aggregate of
patients who recovered from perforation without any other
medical incidents stated above.
Evaluation of demographic and clinical variables
according to clinical outcomes
Demographics of patients, including sex, age, comorbidity,
and anatomical conditions, were noted. To evaluate the
Fig. 1 During 10 years, a total of 11,048 ERCPs were performed in
two tertiary medical centers. Among these, 68 patients (0.62 %) who
experienced perforation with radiologic, endoscopic, or surgical
evidence were identified
3294 Surg Endosc (2012) 26:3293–3300
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severityofcomorbidity,theCharlsoncomorbidityindexscore
was measured [4]. Clinical variables that could potentially
affect the outcome of the procedure, e.g., malignant cause,
urgency of procedure, or ERCP procedural time that was
recorded after patients were consciously sedated with intra-
venous midazolam, also were collected. Several well-known
clinical factors associated with perforation after ERCP,
including the time of detection, location of perforation, or
mechanism of perforation, were reviewed, and we also
assessed the symptoms and signs of patients. Among these,
abdominal pain was defined as pain so severe that patients
needed analgesics, and rebound tenderness was defined as
peritoneal irritation, which was documented by a physician.
We also assessed the management methods that were used
based on the clinical situations and decisions of physicians
after detection of perforation. The study was approved by the
institutionalreviewboardateachparticipatingmedicalcenter.
Statistics
Categorical variables were compared by the chi-square test
or Fisher’s exact test. Continuous variables were compared
by the Mann-Whitney U test. Using variables with P\0.1
for simple logistic regression analysis, step-wise multiple
logistic regression analysis was performed to identify
variables affecting the clinical outcomes. Two-sided
P values\0.05 were considered statistically significant. All
statistical analyses were performed by using the SPSS?
version 17.0 for Windows (SPSS Inc, Chicago, IL).
Results
Overall characteristics of patients
Of a total of 68 patients, females were predominant (39/68,
57.4 %), and the median age was 65.0 (range, 23–89) years.
The most common cause of ERCP was common bile duct
stonewithorwithoutcholangitis(n = 25,36.8 %).Twenty-
twopatients(32.4 %)underwentERCPduetomalignancies,
andthemostcommonmalignancywasextrahepaticbileduct
cancer (n = 9, 13.2 %). ERCP for therapeutic purpose was
performed in 76.5 % of patients, and 15.5 % of ERCP cases
were urgent. In less than half of the cases (45.6 %), the
procedure time took more than 30 min. Six patients had a
history of subtotal gastrectomy with Billroth II reconstruc-
tion, and 16 patients had periampullary diverticulum.
Among clinical manifestations after perforation, abdominal
painandreboundtendernessshowedasignificantlydifferent
distribution between the groups with good and poor out-
comes (P = 0.01). Compared with abdominal pain, which
two-thirds of patients experienced, only 15 % of patients
showed rebound tenderness.
In terms of management and clinical outcomes, only
nine patients (13.2 %) received emergent surgery without
statistical difference between the two groups. Twelve
patients who underwent conservative treatment (1 in the
group with poor outcomes and 11 in the group with good
outcomes) received elective surgery after recovery from
perforation. Biliary drainage was performed in 32 patients
(47.1 %), and both endoscopic and percutaneous biliary
drainage were used almost equally. However, percutaneous
drainage (PCD) of collected fluid was more necessary in
the group with poor outcomes (P = 0.01). According to the
definition of methods, duration of hospital stay and use of
intravenous antibiotics were longer in the group with poor
outcomes (P\0.01). There were four deceased patients in
the group with poor outcomes (Table 1).
Characteristics and mechanisms of perforations
Perforations were most frequently detected by fluoroscopy,
and 46 cases of perforations (67.6 %) were identified
during ERCP. After ERCP, CT was the most useful method
to detect perforation. Between the groups with good and
poor outcomes, there was a difference in the time of
detection with a borderline significance (during ERCP
vs. after ERCP, P = 0.05). In particular, in one patient who
experienced clinical deterioration after ERCP, perforation
was only found with explorative laparotomy, because
endoscopic or radiologic examination, including CT,
showed no evidence of perforation.
Regarding the location, the periampullary region was
the most common site, followed by the common bile duct.
However, perforation at the duodenal wall remote from the
ampulla was relatively frequent in the group with poor
outcomes, and there was a borderline significant difference
in the location between the duodenal wall remote from the
ampulla and other sites (P = 0.09). Regarding the mecha-
nism of perforation, an endoscopic sphincterotomy (EST)
and a catheter or guidewire were the common causes.
Similar to the location, perforation by endoscope was fre-
quent in the group with poor outcomes, and there also was
a borderline significant difference in mechanisms between
an endoscope and other mechanisms (P = 0.09).
In contrast to the median 14.5 h needed to detect per-
foration in the group with poor outcomes, the median time
to detect perforation in the group with good outcomes was
0 h, which meant detection during ERCP (P = 0.03).
However, there was no difference in the delayed detection
rate between the two groups (Table 2).
Prediction of patients with poor clinical outcomes
For analysis of clinical factors that were associated with
outcomes, we conducted a logistic regression analysis.
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By simple logistic regression analysis, the following vari-
ables were significantly or borderline significantly associ-
ated with poor outcomes (P\0.1): detection after ERCP,
perforation at duodenal wall remote from the ampulla,
perforation
decreased systolic blood pressure more than 20 %. Because
perforation by endoscope was significantly correlated with
perforation at the duodenal wall remote from the ampulla
by endoscope,reboundtenderness,and
Table 1 Overall characteristics of patients
Poor outcomes (n = 10) Good outcomes (n = 58)Total (n = 68)
P value
Sex (male, %) 6 (60) 23 (39.7)29 (42.6)0.31
Median age (yr)64.5 (40–86)65.5 (23–89) 65 (23–89)0.81
Malignancy (%) 4 (40)18 (31) 22 (32.4) 0.72
[0.99
[0.99
Therapeutic ERCP (%)
Urgent case (%)a
8 (80) 44 (75.9)52 (76.5)
1 (10)8 (13.8) 9 (15.5)
ERCP procedure
Sphincterotomy (standard/needle knife)4/3 (40/30) 26/11 (44.8/19)
16 (27.6)d
9 (15.5)d
30/14 (44.1/20.6)
20 (29.4)d
9 (13.2)d
[0.99
0.47
Stone removal 4 (40)
Balloon dilation
ERCP time[30 min
CBD dilation[1 cm
Comorbidities (%)
0 (0)
0.34
[0.99
0.73
5 (50 26 (44.8)31 (45.6)
5 (50)35 (60.3)40 (58.8)
4 (40) 15 (25.9)
5 (8.6)b
19 (27.9)0.45
Diabetes0 (0)
5 (7.4)
Liver cirrhosis 2 (20)6 (10.3)
3 (5.2)b
8 (11.8)
Cardiovascular disease 1 (10)
4 (5.9)
Chronic renal failure1 (10) 1 (1.7)2 (2.9)
COPD 0 (0)1 (1.7) 1 (1.5)
Charlson comorbidity index score (median) 2 (0–8)1 (0–8)1 (0–8) 0.31
Anatomical conditions of difficult cannulation (%)
STG BII1 (10) 5 (8.6) 6 (8.8)
[0.99
0.43 PAD 1 (10)15 (27.8) 16 (25.0)
Symptom and signs after perforation
Abdominal pain 10 (100)35 (60.3)45 (66.2)0.01
Rebound tenderness
Decreased sBP[20 % than usual
Increased HR[20 % than usual
Fever[38 ?C
Initial treatment (%)
5 (50) 5 (8.9)10 (15.2)0.01
2 (20) 1 (1.7) 3 (4.4) 0.05
6 (60.0) 20 (34.5) 26 (38.2)0.17
5 (50.0) 22 (37.9)27 (39.7)0.50
0.61
Conservative treatment8 (80.0)51 (87.9)59 (86.8)
Emergent surgery2 (20.0)
3 (30.0)c
7 (12.1)9 (13.2)
32 (47.1)c
Biliary drainage (%)
29 (50.0)0.31
[0.99
[0.99
0.01
\0.01
\0.01
ERBD2 (20.0)16 (27.6)18 (26.5)
PTBD2 (20.0)13 (22.4) 15 (22.1)
Percutaneous drainage (%)5 (50.0)6 (10.3)11 (16.2)
Hospital stay (median, day)37.5 (7–80)12.5 (0–69)13.0 (0–80)
Duration of intravenous antibiotics (median, day) 36.0 (7–73) 9.5 (0–43)11 (0–73)
Mortality (%)4 (40.0) 0 (0.0)4 (5.9)
ERCP endoscopic retrograde cholangiopancreatography, CBD common bile duct, COPD chronic pulmonary obstructive disease,
STG BII subtotal gastrectomy with Billroth II reconstruction, PAD periampullary diverticulum, sBP systolic blood pressure, HR heart rates,
ERBD endoscopic retrograde biliary drainage, PTBD percutaneous transhepatic biliary drainage
aUrgent case meant that the patient received procedures mainly because of cholangitis in the emergency room
bOne patient had both diabetes and cardiovascular disease
cOne patient received both ERBD and PTBD
dThree patients received both stone removal and balloon dilation
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(P\0.001, data not shown), we finally incorporated per-
foration by endoscope, rather than the location of perfo-
ration, into a step-wise multiple logistic regression analysis
with other variables. As a result, only perforation by
endoscope and rebound tenderness showed statistically
significant association with poor outcomes (odds ratio: 13.7
and 7.3, respectively; Table 3).
Discussion
Perforation associated with ERCP is the most serious
complication to avoid, because it can potentially threaten
the life of patients. Consequently, studies regarding this
complication should be necessary; however, there have
been only a few reports with a limited number of cases,
mainly because of its rarity. Furthermore, most studies
focused on the risk factors or managements [2, 6, 8, 13];
there was limited study about the clinical outcomes of these
patients. Based on this background, we purposed to evaluate
the clinical outcomes of patients from a large number of
cases and analyze the clinical factors associated with them.
In this study, the rate of perforation associated ERCP
during approximately 10 years was 0.62 % (68/11,048),
which was comparable to other studies, with rates of
approximately 0.1–1.0 % [6–8, 10]. Although nine patients
underwent emergent surgery, most of the patients (58/68,
85 %) fully recovered from this complication irrespective
of emergent surgery. As a result, perforation after ERCP
was a generally manageable complication; however, it
should be noted that there were four deceased patients
(5.9 %), a rate that was comparable to the 3–20 % rates of
other recent studies [1, 2, 8, 12, 14, 15].
To analyze the clinical factors associated with clinical
outcomes, we divided the patients into two groups and com-
pared the clinical parameters between them. As a result, some
clinical manifestations and the necessity of PCD were statis-
tically associated with the group with poor outcomes. How-
ever, abdominal pain was not a reliable symptom for poor
outcome, because it was nonspecific and frequently observed
in patients with perforation, which also was described in
another study [2]. By contrast, rebound tenderness should be
consideredtobeanalarmingsign,because itmeantperitoneal
irritation from peritonitis. The above study reported that
Table 2 Characteristics and
mechanisms of perforation
ERCP endoscopic retrograde
cholangiopancreatography,
CT computed tomography
aDuring ERCP versus After
ERCP
bDuodenal wall remote from
ampulla vs. other sites
cEndoscope vs. other
mechanisms
dDelayed detection meant
identification of perforation
after oral intake of food or after
more than 12 h in case of no
oral intake
Poor outcomes
(n = 10)
Good outcomes
(n = 58)
Total
(n = 68)
P value
Time of detection and initial detection method (%) 0.05a
During ERCPEndoscope 3 (30)11 (19) 14 (20.6)
Fluoroscopy1 (10)31 (53.4) 32 (47.1)
After ERCP Chest radiograph0 (0) 1 (1.7) 1 (1.5)
Abdomen radiograph0 (0) 3 (5.2)3 (4.4)
Abdomen CT5 (50)12 (20.7) 17 (25)
Explorative laparotomy1 (10) 0 (0)1 (1.5)
Location of perforation (%)0.09b
Duodenal wall remote from ampulla 3 (30)5 (8.6)8 (11.8)
Other sites
Duodenal periampullary region 4 (40)27 (46.6)31 (45.6)
Common bile duct1 (10)15 (25.9)16 (23.5)
Common hepatic duct0 (0)3 (5.2) 3 (4.4)
Gallbladder 1 (10) 2 (3.4)3 (4.4)
Jejunal afferent limb 1 (10) 3 (5.2)4 (5.9)
Gastroduodenal anastomosis0 (0) 1 (1.7)1 (1.5)
Unknown 0 (0)2 (3.4) 2 (2.9)
Mechanisms of perforation (%) 0.09c
Endoscope4 (40) 9 (15.5)13 (19.1)
Other mechanisms
Endoscopic sphincterotomy4 (40)21 (36.2)25 (36.8)
Catheter or guidewire1 (10) 22 (37.9)23 (33.8)
Resection by snare 0 (0) 2 (3.4)2 (2.9)
Unknown1 (1) 4 (6.9)5 (7.4)
Time to detect (median, hour)
Delayed detection (%)d
14.5 (0–175) 0 (0–816)0 (0–816)0.03
5 (50)13 (22.4)18 (26.5)0.12
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Table 3 Simple and multiple logistic regression analysis of clinical factors according to poor outcomes
Simple logistic regressionMultiple logistic regression
OR (95 % CI)
P valueOR (95 % CI)
P value
Age1 (0.9–1)0.79
Sex
Male1
Female2.3 (0.6–9)0.24
Malignancy
Benign1
Malignant0.7 (0.2–2.7)0.58
Purpose of ERCP
Diagnostic1
Therapeutic
Urgencya
1.3 (0.2–6.7)0.78
Scheduled1
Urgent0.7 (0.1–6.2)0.75
ERCP time
B30 min
[30 min
Comorbidities
1
1.2 (0.3–4.7)0.76
Without1
With1.9 (0.5–7.7)0.36
Anatomical condition of difficult cannulation
Normal1
STG BII 1 (0.1–10) 0.97
PAD0.3 (0–2.5)0.26
Time of detection
During ERCP11
After ERCP4.7 (1.2–19.1) 0.03 8 (0.8–84.7)0.09
Location
Other sites except duodenal
wall remote from ampulla
1
Duodenal wall remote from ampulla4.5 (0.8–23.3) 0.07
Mechanism
Other mechanisms except endoscope11
Endoscope3.6 (0.9–15.5)0.0813.7 (1.3–148.2) 0.03
Time to detect1 (1–1) 0.67
Abdominal pain
No 1.0
YesNA
[0.99
Rebound tenderness
No11
Yes
Decreased sBP[20 % than usual
No
10.6 (2.3–49.5)
\0.01 7.3 (1.2–44)0.03
11
Yes
Increased HR[20 % than usual
No
14.3 (1.2–175.7) 0.04 8.1 (0.5–124.2)0.13
1
Yes 2.9 (0.7–11.3)0.14
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peritonitisistheonlyfindingthatindicatesimmediatesurgical
exploration [2], and our study showed that it also was associ-
ated with a grave clinical course.
In terms of detailed characteristics and mechanisms of
perforation, detection during ERCP was possible in approxi-
matelytwo-thirds(n = 46,67.6 %)ofpatients,aratethatwas
comparabletothoseofpreviousstudies:67–78 %[1,8,9,12,
14, 15]. Like previous studies that reported that early recog-
nition may improve clinical outcomes [1, 11, 14], detection
during ERCP was associated with good clinical outcomes
with a borderline significance (P = 0.05), and the median
time to detection in the group with good outcomes was sig-
nificantly shorter than that in the group with poor outcomes
(0 h in group with good outcomes vs. 14.5 h in group with
poor outcomes, P = 0.03). Meanwhile, the group with poor
outcomes was borderline significantly associated with perfo-
ration at the duodenal wall remote from the ampulla and
perforation byendoscope (P\0.1),andthe twofactors were
strongly correlated with each other (P\0.001), findings that
agreed with studies [8, 11, 15]. Previous studies classified
perforations as follows: (1) periampullary perforation fre-
quentlycausedbysphincterotomyorcommonbileductinjury
mainly caused by catheter or guidewire that was manageable
bynonoperativemethods;and(2)bycontrast,lateralduodenal
wall injury mainly associated with bowing of endoscope or
endoscopetorqueagainstafixedstructurethatusuallyneeded
immediatesurgery[8,11,15].Inadditiontotheabovestudies,
our results also showed that the location and mechanism of
perforation were associated with both management methods
as well as clinical outcomes.
Compared with the previous studies that mainly focused
on the surgical aspects [2, 3, 15], we tried to find the
clinical outcomes after perforations in this study. It cannot
be denied that timely surgical intervention is critical;
however, it should be noted that emergent surgical inter-
vention did not mean a poor clinical outcome because of
advanced supportive care methods and surgical techniques.
Considering that perforation after ERCP is usually an
unexpected event despite several studies that reported the
risk factors [6, 8], the more important thing to consider is to
expect the clinical course and intervene it in a timely
fashion. In this aspect, our study showed that the peritoneal
irritation sign and perforation by endoscope are critical not
only as surgical indications but also as factors of grave
outcomes, including mortality, which are results that were
similar to those of another study [9]. Additionally, the
timing of detection, which also was reported in previous
studies [11], showed borderline significant association with
poor outcomes.
In this study, there were the following limitations. First,
this is a retrospective study, and the data were acquired
from two medical centers in a collaborative effort. Second,
the definition of the group with poor clinical outcomes was
somewhat arbitrary, because there was no consensus about
this. Despite such a limitation, however, this was one of the
studies with the largest number of cases regarding perfo-
ration associated with ERCP, and it may help us to predict
clinical outcomes and make a plan for them.
Conclusions
Perforation after ERCP was a rare but unavoidable com-
plication. Although most patients fully recovered from it
Table 3 continued
Simple logistic regression Multiple logistic regression
OR (95 % CI)
P value OR (95 % CI)
P value
Fever[38.0 ?C
No1
Yes 1.6 (0.4–6.3)0.47
Management
Conservative treatment1
Emergent surgery 1.8 (0.3–10.4)0.5
Biliary drainage
No1
Yes 0.4 (0.1–1.8)0.25
Percutaneous drainage
No1
Yes0.9 (0.2–4.6) 0.87
OR odds ratio, CI confidence interval, ERCP endoscopic retrograde cholangiopancreatography, STG BII subtotal gastrectomy with Billroth II
reconstruction, PAD periampullary diverticulum, NA not applicable, sBP systolic blood pressure, HR heart rates
aUrgent case meant that the patient received procedures mainly because of cholangitis at the emergency room
Surg Endosc (2012) 26:3293–33003299
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Page 8

without any other critical problems, some patients experi-
enced a grave clinical course, including mortality. Among
many clinical parameters, perforation by endoscope and
rebound tenderness was associated significantly with poor
clinical outcomes. Finally, watchful monitoring and a
timely intervention are mandatory in patients with such
clinical factors.
Acknowledgments
patients. Our study was not supported by any grant.
The authors appreciate all of the participating
Disclosures
with respect to this manuscript.
The authors declared no potential conflicts of interest
References
1. Assalia A, Suissa A, Ilivitzki A, Mahajna A, Yassin K,
Hashmonai M, Krausz MM (2007) Validity of clinical criteria in
the management of endoscopic retrograde cholangiopancreatog-
raphy related duodenal perforations. Arch Surg 142:1059–1064
2. Avgerinos DV, Llaguna OH, Lo AY, Voli J, Leitman IM (2009)
Management of endoscopic retrograde cholangiopancreatogra-
phy: related duodenal perforations. Surg Endosc 23:833–838
3. Booth FV, Doerr RJ, Khalafi RS, Luchette FA, Flint LM Jr
(1990) Surgical management of complications of endoscopic
sphincterotomy with precut papillotomy. Am J Surg 159:132–135
discussion 135–136
4. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new
method of classifying prognostic comorbidity in longitudinal
studies: development and validation. J Chronic Dis 40:373–383
5. Christensen M, Matzen P, Schulze S, Rosenberg J (2004) Com-
plications of ERCP: a prospective study. Gastrointest Endosc
60:721–731
6. Cotton PB, Garrow DA, Gallagher J, Romagnuolo J (2009) Risk
factors for complications after ERCP: a multivariate analysis of
11,497 procedures over 12 years. Gastrointest Endosc 70:80–88
7. Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers
WC, Liguory C, Nickl N (1991) Endoscopic sphincterotomy
complications and their management: an attempt at consensus.
Gastrointest Endosc 37:383–393
8. Enns R, Eloubeidi MA, Mergener K, Jowell PS, Branch MS,
Pappas TM, Baillie J (2002) ERCP-related perforations: risk
factors and management. Endoscopy 34:293–298
9. Fatima J, Baron TH, Topazian MD, Houghton SG, Iqbal CW, Ott
BJ, Farley DR, Farnell MB, Sarr MG (2007) Pancreaticobiliary
and duodenal perforations after periampullary endoscopic pro-
cedures: diagnosis and management. Arch Surg 142:448–454
discussion 454–445
10. Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME,
Dorsher PJ, Moore JP, Fennerty MB, Ryan ME, Shaw MJ, Lande
JD, Pheley AM (1996) Complications of endoscopic biliary
sphincterotomy. N Engl J Med 335:909–918
11. Howard TJ, Tan T, Lehman GA, Sherman S, Madura JA, Fogel E,
Swack ML, Kopecky KK (1999) Classification and management of
perforations complicating endoscopic sphincterotomy. Surgery
126:658–663 discussion 664–655
12. Kim JH, Yoo BM, Kim MW, Kim WH (2009) Management of
ERCP-related perforations: outcomes of single institution in
Korea. J Gastrointest Surg 13:728–734
13. Krishna RP, Singh RK, Behari A, Kumar A, Saxena R, Kapoor
VK (2011) Post-endoscopic retrograde cholangiopancreatography
perforation managed by surgery or percutaneous drainage. Surg
Today 41:660–666
14. Morgan KA, Fontenot BB, Ruddy JM, Mickey S, Adams DB
(2009) Endoscopic retrograde cholangiopancreatography gut per-
forations: when to wait! When to operate! Am Surg 75:477–483
discussion 483–474
15. Stapfer M, Selby RR, Stain SC, Katkhouda N, Parekh D, Jabbour N,
Garry D (2000) Management of duodenal perforation after
endoscopic retrograde cholangiopancreatography and sphincter-
otomy. Ann Surg 232:191–198
3300 Surg Endosc (2012) 26:3293–3300
123