choledochoduodenal fistula after the placement of a

□ CASE REPORT □

Choledochoduodenal Fistula after the Placementof a Partially Covered Metal Stent for

Unresectable Pancreatic Cancer

Daisuke Masuda, Takeshi Ogura, Akira Imoto, Saori Onda, Tatsushi Sano, Wataru Takagi,

Atsushi Okuda 1, Toshihisa Takeuchi, Shinya Fukunishi,

Takuya Inoue and Kazuhide Higuchi

Abstract

A 75-year-old Japanese man with type 2 diabetes mellitus suffered from unresectable pancreatic head can-

cer and was admitted to our institution due to acute cholangitis. A partially covered metal stent was placed at

that time. 11 months later, he was readmitted for acute cholangitis. Upper endoscopy revealed complete stent

distal migration and a small hole on the oral side of the ampulla. While attempting cannulation into the hole,

an upstream biliary tract was revealed. Accordingly, we diagnosed the patient to have a choledochoduodenal

fistula. After metal stent removal and balloon dilation, we placed two 7 Fr plastic stents, which successfully

relieved the patient’s cholangitis.

Key words: choledochoduodenal fistula, biliary stricture, metal stent migration, acute cholangitis,

unresectable pancreatic cancer

(Intern Med 55: 1591-1597, 2016)(DOI: 10.2169/internalmedicine.55.6060)

Introduction

Choledochoduodenal fistula (CDF) - a type of internal

bilioenteric fistula - is an abnormal connection between the

common bile duct and the duodenum (1). The primary

causes of CDF are choledocholithiasis and a penetrating

peptic ulcer (2, 3). CDF is also a relatively rare, delayed

complication of metal stent placement, which has been re-

ported to be caused by bile duct wall injury due to stent mi-

gration or the sharp end of the metal stent with a poor prog-

nosis (4-9). We herein present a rare case of CDF after the

placement of a partially covered metal stent for distal com-

mon bile duct obstruction in a patient with unresectable pan-

creatic cancer.

Case Report

In September 2008, a 75-year-old Japanese man with type

2 diabetes was referred and admitted to our institution due

to a high fever and jaundice. On physical examination his

conscious was clear, blood pressure was 98/56 mmHg, pulse

was 125 beats/min, and body temperature was 40.2°C. His

skin and eyes showed yellow pigmentation. Laboratory tests

on admission revealed the following results: leukocyte

count, 16,280/μL; C-reactive protein (CRP) level, 3.1 mg/

dL; total bilirubin level, 4.0 mg/dL; aspartate aminotrans-

ferase (AST) level, 341 IU/L; alanine aminotransferase

(ALT) level, 261 IU/L; lactate dehydrogenase (LDH) level,

288 IU/L; alkaline phosphatase (ALP) level, 1,296 IU/L;

and gamma-glutamyl transpeptidase (GGT) level, 711 IU/L.

Levels of cancer antigen (CA) 19-9, serum glucose, and he-

moglobin A1c (HbA1c) were elevated at 2,484 IU/L, 394

mg/dL, and 9.5%, respectively. Renal dysfunction was not

observed.

Ultrasonography showed intrahepatic bile duct dilation

and a hypoechoic lesion on the head of the pancreas. Dy-

namic computed tomography (CT) and magnetic resonance

The Second Department of Internal Medicine, Osaka Medical College, Japan

Received for publication June 26, 2015; Accepted for publication December 22, 2015

Correspondence to Dr. Daisuke Masuda, [email protected] and [email protected]

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Figure　1.　Enhanced computed tomographic images. (a) Pneumobilia can be observed in the intra-hepatic duct (red arrows) 9 month after the first stent insertion. (b) The covered SEMS (black arrow) can be seen outside the common bile duct, thus stent migration was suspected. (c) Multiple liver me-tastases are present (yellow arrows) with pneumobilia (red arrow).

aa

bb cc

imaging (MRI) further revealed a 40 mm, irregular, mar-

ginal, poorly enhanced mass on the head of the pancreas,

which had invaded into the distal bile duct, superior mesen-

teric vein, and artery. Magnetic resonance cholangiopancrea-

tography (MRCP) revealed an obstruction of the common

bile and main pancreatic ducts. According to the laboratory

results and imaging findings, acute cholangitis with sepsis

due to a biliary tract obstruction was diagnosed. We per-

formed urgent endoscopic retrograde cholangiopancreatogra-

phy (ERCP) with successful selective biliary cannulation

and endoscopic prosthesis. Blood and bile cultures revealed

Gram-negative enteric bacteria. After an improvement of

acute cholangitis, we performed ERCP again for biliary

brush cytology, which revealed positive results. Therefore,

we diagnosed the patient with unresectable pancreatic head

cancer and placed a partially covered, self-expandable metal

stent (SEMS) (10 mm×60 mm covered WALLSTENT; Bos-

ton Scientific Japan, Tokyo, Japan) in the distal bile duct.

However, a few days after stent placement, the metal stent

had proximally migrated. Thus, we inserted an additional

SEMS through the previous SEMS, using the “stent through

stent” method, which successfully relieved the patient’s

acute cholangitis and jaundice.

Nine months later, cholangitis appeared again during che-

motherapy (gemcitabine, 1,000 mg/m2). Conservative treat-

ment was performed for acute cholangitis because enhanced

CT revealed pneumobilia in the intrahepatic duct and we be-

lieved that the covered SEMS were not obstructed or had

migrated (Fig. 1a). Eleven months after the first SEMS in-

sertion, the enhanced CT revealed suspected stent migration

to the duodenum and multiple liver metastases with pneu-

mobilia in the intrahepatic duct (Fig. 1b, c). CT and MRCP

showed an obstruction of the common bile and main pancre-

atic ducts, as well as a bar-shaped high intensity signal out-

side the biliary tract (Fig. 2). According to these findings,

stent distal migration was suspected. Upper endoscopy con-

firmed that the covered WALLSTENT had completely mi-

grated to the duodenum (Fig. 3a) and revealed a small hole

on the oral side of the ampulla (Fig. 3b). Duodenal stenosis

due to cancer invasion was also noted on the anal side of

the small hole and around the ampulla. When we attempted

to perform cannulation through the small hole, a proximal

biliary tract was revealed (Fig. 4). Therefore, we diagnosed

the patient has having a CDF, which had a negative biopsy

result, and identified that the orifice of the CDF was con-

nected to the proximal edge of the biliary stricture. We re-

moved the covered SEMS using biopsy forceps and a re-

trieval basket and placed two 7 Fr double-pigtail plastic

stents through the CDF after balloon dilation of the CDF

(Fig. 5) without any adverse events. The patient’s cholangitis

Intern Med 55: 1591-1597, 2016 DOI: 10.2169/internalmedicine.55.6060

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Figure　2.　Magnetic resonance cholangiopancreatography shows obstruction of the common bile and main pancreatic ducts, as well as a bar-shaped high intensity signal (red arrows) outside the biliary tract. The CDF cannot be seen, however, it is indicated by the yellow arrow and line.

was successfully relieved with this endoscopic treatment,

however, he died because of his worsened condition due to

the progression of pancreatic cancer 2 months later after re-

intervention without another interventional treatment. We

retrospectively evaluated the CT image (Fig. 6), and the

covered SEMS remained in the bile duct without migration

3 months after the first insertion, however, 9 months later

the SEMS migrated to the duodenum, and the size of the

primary pancreatic cancer was gradually reduced.

Discussion

Various etiologies of CDF have been reported, such a

penetrating peptic ulcer (1), choledocholithiasis (2), hepato-

biliary (5, 8, 9) and pancreatic cancer (6, 7), and iatrogenic

injury, including that by an endoscopic prosthesis (4-9).

CDF is a relatively rare, delayed complication of metal stent

placement, which is related to bile duct wall injury due to

stent migration or the sharp end of the metal stent (9). CDF

cases associated with SEMS were identified in the PubMed

database using the search terms “choledochoduodenal fis-

tula” and “self-expandable metallic stent,” or “metal stent,”

and 6 additional cases were found (hereafter referred to as

reference cases). The characteristics of these 6 cases and the

present case are shown in Table. Five CDFs were located at

the bulbus with a large ulcer, however, only 2 cases of small

CDF occurred, including the present case, and were located

at the descending portion of the duodenum. The inserted

stents were a WALLSTENT for 2 cases and the WallFlex

stent for 1 case, and the Niti-S uncovered stent for 1 case,

in addition to our present case, which were inserted by the

“stent through stent” method. The WALLSTENT has a high

axial force, which is the recovery force that leads to

straightening of a WALLSTENT; therefore, a bile duct with

a high axial force tends to kink at the proximal edge of the

straightening stent (10, 11), and this stent has a sharp end.

This force and the sharp end of the stent are thought to in-

jure the bile duct at the proximal edge of the stent and form

a CDF. Indeed, in this present case, the CDF connected to

the bile duct around the proximal edge. Moreover, the in-

serted stents in present case completely migrated distally,

and many investigators have reported covered metal stent

migration. Nakai et al. (11) reported that chemotherapy and

a covered SEMS with a low radial force were significant

risk factors for covered metallic stent migration in patients

with a distal malignant biliary obstruction due to pancreatic

cancer. Although the WALLSTENT also has a high radial

force, in addition to a high axial force, chemotherapy was

thought to reduce the size of the primary pancreatic cancer

lesion because of necrosis and reduction of extra compres-

sion to the biliary tract from primary pancreatic cancer

(Fig. 6), which may have resulted in radial force reduction.

Chemotherapy was also reported to be a factor of forming

a CDF (6). According to the reference cases, chemotherapy

was performed for 3 of 6 cases, in addition to the present

case. Chemotherapy was thought to result in necrosis of the

primary pancreatic cancer lesion and around invasive tissues

and organs, thus the bile duct wall was also vulnerable be-

cause of invasion. Cancer invasion to the common bile duct

and duodenum is another factor for the formation of a CDF.

The association between CDF and cancer, including ampul-

lary, duodenal, gallbladder, biliary, and pancreatic cancers, is

rare (12). For 1 of the 6 reference cases, the result of a bi-

opsy at the CDF was positive. In the present case, pancre-

atic cancer directly invaded both the duodenum on the anal

side of the ampulla and the distal biliary tract, and the CDF

was connected to the proximal edge of the distal bile duct

obstruction, however, the biopsy of the duodenum at the

CDF was negative. Although chemotherapy might influence

the formation of a CDF, cancer invasion was not speculated

to be a factor due to the negative biopsy results in the pre-

sent case.

Increased intraductal pressure of the biliary tract is an-

other factor of forming a CDF. Severe cholangitis, espe-

cially, caused from a bile duct obstruction due to distal mi-

gration of a covered SEMS influenced vulnerable bile duct

walls by increasing the intraductal biliary pressure. Accord-

ing to Lee et al. (9), the formation and rupture of a cystic

lesion between the common bile duct and the duodenum fol-

lowing a bile duct obstruction could create a CDF. Although

those findings could not be observed with CT, the biliary

pressure was speculated to be increased because of severe

acute cholangitis due to the migration of a covered SEMS in

the present case. The mechanism of forming a CDF could

not be verified, however, bile duct injury due to a high axial

force and sharp end of a SEMS, chemotherapy, and acute

cholangitis due to SEMS migration were likely involved in

the present case.

It is difficult to diagnose and detect a CDF, and it is typi-

cally detected incidentally on endoscopy. Abdominal pain, a

high fever, jaundice, nausea, and vomiting can be symptoms,

however, many cases of CDF will present with no or non-

specific symptoms. According to the reference cases and our


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Figure　3.　(a) An upper endoscopic image shows that the covered SEMS completely migrated from the bulb to the descending portion of the duodenum.The ampulla of Vater is indicated by the white circles. (b) An upper endoscopic image after SEMS removal shows a small hole (white arrow) on the oral side of the ampulla and bile juice flowing from the hole.

aa bb

Figure　4.　Endoscopic (a) (b) images and fluoroscopic (c) image during ERCP. (a) A small hole (white arrow) on the oral side of the ampulla is seen and the ampulla of Vater is recognized on the anal side of the small hole (green arrow). (b) (c) Following cannulation of the small hole under fluoro-scopic guidance, cholangiography was revealed.

aa bb

cc

present case, cholangitis and bleeding from a CDF as initial

symptoms was observed for 3 cases each; 3 cases had ‘tarry

stool’, ‘hematemesis’ and ‘melena’ as symptoms of bleeding

in large CDF at the bulbus; and 1 case of large CDF and 2

cases of small CDF had cholangitis. CT revealed pneumo-

bilia in some cases of CDF (13, 14) due to a connection be-


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Figure　5.　Endoscopic (a) and fluoroscopic (b) images during stent placement. Two double pig-tail type plastic stents are placed after balloon dilation of the CDF.

aa bb

Figure　6.　Change in the CT images of the SEMS inserted on the first admission, 3 months later, and 9 months later. The primary pancreatic cancer is indicated with red arrows. CT images show the SEMS inserted on the first admission, 3 months later, and 9 months later. The SEMS is seen in the bile duct 3 months after insertion, but it is outside of the bile duct 9 months later. The size of the primary pancreatic cancer is reduced.

tween the duodenum and biliary tract, although it is a com-

mon finding when there is no metal stent occlusion. In the 6

reference cases, pneumobilia was observed for 1 large CDF

case, not including the present case.

Conventional surgical treatment has generally been per-

formed for large symptomatic CDFs (1). However, following

a report by Tanaka et al. in 1983, endoscopic treatment has

become the first choice (2). Endoscopic treatment is per-

formed to prevent acute cholangitis (15, 16), especially if

the CDF can be healed with re-insertion of a covered metal

stent (15) or through endoscopic closure (17). In cases of

both duodenal and biliary obstruction caused by pancreatic


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Table.　Characteristics of CDF Cases Associated with SEMS.

Nd: not description

cancer, the use of a double stent method has been recently

reported (18-20). Mutignani et al. (18) classified three types

of bilio-duodenal obstruction according to the duodenal

stricture in relation to the papilla. According to these crite-

ria, the present case was thought to be compatible with type

II, which affects the second part of the duodenum with in-

volvement of the papilla. Approaching the papilla by insert-

ing a duodenoscope through the duodenal stent and biliary

cannulation and inserting the delivery system of SEMS

through the mesh of the duodenal stent are necessary fol-

lowing duodenal stenting under fluoroscopic guidance for

the placement of a biliary metal stent in cases of type II

bilio-duodenal stricture, however, these procedures are gen-

erally difficult through the mesh of the stent. Among the

reference cases, the cases of large CDF at the bulbus were

treated with EMS exchange from the ampulla, insertion of a

duodenal stent, or embolization of the feeding artery for

bleeding, however, the CDFs remained. The small CDF case

at the duodenal descending portion was treated with ENBD,

which resulted in the disappearance of the CDF. None of the

reference cases of CDF had duodenal obstruction. Double

metal stenting has been recently performed for duodenal and

biliary obstruction and is another treatment option for a

CDF. However, we previously did not select a metal stent

for use except in cases of malignant biliary stricture, includ-

ing CDF. Furthermore, CDF cases associated with SEMS

placement in advanced cancer have a poor prognosis (4-6),

and a long-term survival is not expected. As long stent

patency was not needed, we inserted 2 plastic stents from

the CDF with the successful relief of cholangitis. Indeed,

the prognosis of CDF associated with EMS was poor for 3

cases because all cases were unresectable pancreatic cancer,

biliary cancer, or other organ metastatic cancer. Three of the

5 cases of large CDF at the bulbus and the present case of

small CDF ultimately died due to bleeding, hepatorenal syn-

drome, or cancer progression. Our case died due to the pro-

gression of primary pancreatic cancer 2 months after re-

intervention.

In conclusion, CDF is a rare complication after metal

stent placement, and a small CDF at the duodenal descend-

ing portion is especially rare with successful relief of acute

cholangitis. Endoscopic stent placement through the CDF

may be the first choice of treatment for acute cholangitis.

The authors state that they have no Conflict of Interest (COI).

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choledochoduodenal fistula after the placement of a

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