Predisposing Factors of Bile Duct
Injury After transcatheter
arterial chemoembolization
(TACE) for Hepatic Malignancy
Cardiovasc Intervent Radiol (2002)
Jeong-Sik Yu, South Korea
Abstract
• The purpose of this study was to investigate the
predisposing factors of bile duct injury after
transcatheter arterial chemoembolization(TACE)
for treatment of hepatic malignancy.
• Transcatheter arterial chemoembolization
(TACE) has been generally used for the
treatment of hepatocellular carcinoma and less
frequently for other malignant tumors in the liver
Abstract
• As a complication of TACE, bile duct injury has
been reported intermittently since the
introduction of hepatic arterial embolization
therapy.
• The incidence of bile duct injury after TACE or
hepatic arterial infusion chemotherapy was
12.5% in an autopsy series,
• However, the incidence was very low (in the
range of 0.9%–2.1%) of those in some largeseries follow-up CT studies.
Materials and Methods
• From Dec. 1995 to Nov. 1998 a total of 346
consecutive patients underwent one or more
sessions of TACE for the control of liver
malignancy, including hepatocellular carcinoma
(n=328), cholangiocarcinoma(n= 5), primary
malignant fibrous histiocytoma (n= 1),
metastases from stomach cancer (n =4),
colorectal cancer (n=3), pancreatic cancer (n
=1), gallbladder cancer (n =1),malignant
gastrointestinal stromal tumor (n =1), and
gastrointestinal carcinoid tumor (n =2).
Materials and Methods
• The routine protocol of TACE in our institution
includes 1–20 mL of iodized oil and 10–50 mg of
doxorubicin hydrochloride emulsion,If
possible,the emulsion was injected exclusively
into the tumor feeding segmental or
subsegmental arterial branches followed by
administration of gelatin sponge.
Materials and Methods
• Among the 346 patients, 965 post-TACE followup CTs of 274 patients with detailed records of
TACE, and more than 1-year serial follow-up CT
records were available for a retrospective search
of computerized reports.
• 40 patients had intrahepatic bile duct dilatation,
intraparenchymal fluid collection, or cyst
formation with or without segmental/lobar
parenchymal infarct or atrophic changes.
• The hard copy images of the follow-up CTs and
pre-TACE CTs of the 40 selected patients were
reviewed by two radiologists to determine
whether the CT findings were directly related to
theTACE procedure.
The imaging criteria for diagnosis of
TACE induced bile duct injuries
• disproportionately dilated bile ducts with lobar or
segmental distribution, which were newly
developed after TACE, and a newly developed
cystic lesion accompanied by segmental bile
duct dilatation, with or without surrounding
hyperemia.
• 15 patients had newly developed cystic lesions,
suggesting TACE-induced biloma in addition to
abnormal bile duct dilatations (Fig. 1) another 16
patients showed newly developed abnormal bile
duct dilatations without the cystic lesion (Fig.2).
• The bile duct dilatations in 7 patients were thought
to have been induced by a direct tumor invasion or
by the compression effect of large tumors, and the
cystic lesions in 2 patients were thought to be due
to preexisting simple cysts. These nine patients
were excluded from this study.
Fig. 1. A 49-year-old man with a metastatic tumor from gastric
adenocarcinoma on segment 8 in right lobe of liver.Four-week followup CT after segmental chemoembolization shows a newly developed
cystic lesion suggesting biloma (arrowheads) associated with
irregular, speckled accumulationsof high-density iodized oil in right
lobe of the liver.
Fig. 2. A 57-year-old man with a metastatic tumor from gastric
adenocarcinoma on segment 5 in right lobe of the liver. Three-week
follow-up CT after subsegmental chemoembolization shows a
newly developed segmental bile duct dilatation (arrowheads)
associated with a surrounding, wedge-shaped, inhomogeneous
accumulation of high-density iodized oil.
The factors chosen for comparative
analysis were as follows:
①final diagnosis of the treated tumor.
②Child-Pugh class as a parameter of the liver
profile.
③presence of a grossly detectable portal vein
thrombosis.
④total number of TACE procedures.
⑤selectivity of injection of embolic materials.
⑥amount of the iodized oil, and the use of gelatin
sponge particles.
• For patients with more than one TACE session,
the records of th last session just before the
development of bile duct injury were used.
• In the control group patients with more than one
TACE session, the records at the time of the
most selective TACE were used for comparison.
• The likelihood ratio chi-square test or Fisher’s
exact test with chi-square approximation was
used to comparethe incidence of bile duct
injuries for each assumptive factor.
Results
• With respect to the final diagnoses of the treated tumors,
7 (38.9%) of 18 patients with non-hepatocellular tumors
showed TACE-induced bile duct injuries, which is
significantly higher (p＜0.01) than the 9.7% of patients
with hepatocellular carcinoma (Table 1).
• 29(15.2%) of 191 Child-Pugh class A patients including
all of the non-hepatocellular tumors and hepatocellular
carcinoma patients with or without cirrhosis showed bile
duct injuries, and this incidence was significantly higher
(p＜0.01) than 2 (2.7%) of 74 Child-Pugh class B and C
patients with advanced liver cirrhosis (Table 1).
Table (1)
Results
• The incidences of bile duct injuries with (7/62,
11.3%) or without (24/203, 11.8%) the presence
of gross portal vein thromboses were very
similar, and portal vein thromboses did not
influence the chance of developing bile duct
injuries in this study (p =1.00).
• TACE that included gelatin sponge embolization
following iodized oil and doxorubicin
hydrochloride emulsion appeared to have a
higher incidence of bile duct injuries, however,
the difference was not statistically significant
(p =0.27).
Results
• The amount of iodized oil administered versus
the level of TACE are summarized in Table 2
• The mean amount of iodized oil used in patients
without bile duct injury was slightly higher than in
patients with bile duct injuries.There was no
relationship between the amount of iodized oil
used and bile duct injury in this study.
Table(2)
Discussion
• the incidence of TACE-related bile duct injury
was significantly higher in our patients with
Child-Pugh class A than in those with poor liver
profiles with advanced cirrhosis (Child-Pugh
class B orC). This result implies that the bile
ducts in the advanced cirrhotic liver are more
resistant to ischemic injury from the same
amount of iodized oil and subsequent gelatin
sponge block.
Results
• Regarding the total number of TACE
procedures, patients who underwent five or
more sessions of TACE showed a higher rate of
bile duct injuries (Table 1). However, the
incidence among patients with up to four TACE
sessions and those with five or more sessions
was not significantly different (p= 0.30). The
chance of bile duct injury was significantly higher
(p=0.01) after subsegmental or segmental TACE
than after lobar or more proximal TACE (Table
1).
final diagnosis of the treated tumor
• The high incidence of bile duct injury in nonhepatocellular carcinomapatients also implies
that the selective TACE, in the otherwise normal
liver, may occlude the nonhypertrophied
peribiliary plexus and result in ischemic injury.
incidence of TACE-induced bile
duct is different
• In the present study, 31 (11.3%) out of 274
patients showed TACE-induced bile duct
injuries, an incidence much higher than in
previous reports based on CT evidence but
comparable with an autopsy series(12.5%).
• differences in the patient population and the
TACE technique(The patient populations in
previous reports were limited to patients with
hepatocellular carcinomas arising in cirrhotic
livers and highly selective embolization of the
noncirrhotic liver.
highly selective embolization
• The synergistic effect of highly selective
embolization of the noncirrhotic liver would
increase the chance of ischemic bile duct
injuries due to complete cessation of blood flow
in the capillaries regardless of the total volume
of iodized oil injected into the tumor feeder in
each patient.
• In other words, cirrhotic changes of the liver
parenchyma and selectivity of the catheter tip
during the TACE are more important than the
total volume of the injected iodized oil.
• In the present study, despite the absence
of statistical validation, the percentage of
TACE-induced bile duct injury was higher
in patients with additional gelatin sponge
embolization.
portal vein thrombosis
• There was no significant functional impairment
after TACE in our patients with portal vein
thrombosis. it did not influence the incidence of
bile duct injuries in our study.
• In patients with portal vein thrombosis ,a
compensatory increase of hepatic arterial flow
would induce hypertrophy of the peribiliary
plexus.therefore, portal vein thrombosis may not
be a predisposing factor to bile duct injury.
The number of repeated TACE
• The number of repeated TACE procedures is
one of the well-known predisposing factors to
bile duct injuries,In this study, however, there
could be a possibility of masking the higher
incidence of bile duct injury in patients with
repeated TACE due to the other predisposing
factors.
Conclusion
• the chance of bile duct injury after TACE is
increased in the noncirrhotic liver with a good
liver function by selective embolization of distal
arterial branches.
• While not statistically significant, the additional
use of gelatin sponge fragments, and the
repeated number of TACEs, are also believed to
potentially exacerbate ischemic bile duct injury.
• A prospective study of TACE-induced bile duct
injury is needed to establish other possible
factors predisposing to bile duct ischemia.
Thank you for your attention