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This study investigates the predisposing factors of bile duct injury after transcatheter arterial chemoembolization (TACE) for the treatment of hepatic malignancy. The incidence of bile duct injury after TACE was analyzed using follow-up CT studies.
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Predisposing Factors of Bile DuctInjury 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 large-series 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 feedingsegmental or subsegmental arterial branches followed byadministrationof gelatin sponge.
Materials and Methods • Among the 346 patients, 965 post-TACEfollow-up CTs of 274 patients with detailedrecords of TACE, and more than 1-year serial follow-up CT recordswere available for a retrospective search of computerized reports. • 40 patients had intrahepatic bile duct dilatation, intraparenchymalfluid collection, or cyst formation with or without segmental/lobar parenchymal infarct or atrophic changes. • The hard copyimages of the follow-up CTs and pre-TACE CTs of the 40 selectedpatients were reviewed by two radiologists todetermine whether the CT findings were directly related to theTACE procedure.
The imaging criteria for diagnosis of TACEinducedbile duct injuries • disproportionately dilatedbile ducts with lobar or segmental distribution, which werenewly developed after TACE, and a newly developed cystic lesionaccompanied bysegmental bile duct dilatation, with orwithoutsurrounding hyperemia.
15 patients had newly developed cysticlesions, suggesting TACE-induced biloma in addition to abnormalbile duct dilatations (Fig. 1)another 16 patients showednewly developed abnormal bile duct dilatations without the cysticlesion(Fig.2). • The bile duct dilatations in 7 patientswere thought to have been induced by a direct tumor invasion or bythe compression effect of large tumors, and the cystic lesions in 2 patients were thought to be due topreexisting simplecysts. Thesenine patients were excluded from this study.
Fig. 1. A 49-year-old man with a metastatic tumor fromgastric adenocarcinoma on segment 8 in right lobe of liver.Four-week follow-up CT after segmental chemoembolizationshows 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 fromgastric adenocarcinoma on segment 5 in right lobe of theliver. Three-week follow-up CT after subsegmental chemoembolizationshows a newly developed segmental bile ductdilatation (arrowheads) associated with a surrounding,wedge-shaped, inhomogeneous accumulation of high-densityiodized oil.
The factors chosen for comparative analysis were as follows: ①final diagnosis of the treated tumor. ②Child-Pugh class as aparameter of the liver profile. ③presence of a grossly detectable portalvein 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 thlast session just before the development of bile duct injury wereused. • In the control group patients with more than one TACEsession, the records at the time of the most selective TACE wereused for comparison. • The likelihood ratio chi-square test or Fisher’sexact test with chi-square approximation was used to comparethe incidence of bile duct injuries for each assumptive factor.
Results • With respect tothe final diagnoses of the treated tumors, 7 (38.9%) of 18patients with non-hepatocellular tumors showed TACE-inducedbile duct injuries, which is significantly higher (p＜0.01) than the 9.7% of patients withhepatocellular carcinoma(Table 1). • 29(15.2%) of 191 Child-Pughclass A patients including all of the non-hepatocellular tumorsand hepatocellular carcinoma patients with or withoutcirrhosis showed bile duct injuries, and this incidence wassignificantly higher (p＜0.01) than 2 (2.7%) of 74 Child-Pugh class B and C patients with advanced liver cirrhosis(Table 1).
Results • The incidences of bile duct injuries with (7/62, 11.3%) orwithout (24/203, 11.8%) the presence of gross portal veinthromboses were very similar, and portal vein thrombosesdid not influence the chance of developing bile duct injuriesin this study (p =1.00). • TACE that included gelatin sponge embolization following iodized oil and doxorubicin hydrochlorideemulsion appeared to have a higher incidence ofbile duct injuries, however, the difference was not statisticallysignificant (p =0.27).
Results • The amount of iodized oil administered versus the level ofTACE are summarized in Table 2 • The mean amount ofiodized oil used in patients without bile duct injury wasslightly higher than in patients with bile duct injuries.Therewas no relationship between the amount of iodized oil usedand bile duct injury in this study.
Discussion • the incidenceof TACE-related bile duct injury was significantly higher inour patients with Child-Pugh class A than in those with poorliver profiles with advanced cirrhosis (Child-Pugh class B orC). This result implies that the bile ducts in the advancedcirrhotic liver are more resistant to ischemic injury from thesame amount of iodized oil and subsequent gelatin spongeblock.
Results • Regarding the total number ofTACEprocedures, patients who underwent five or moresessions of TACE showed a higher rate of bile duct injuries(Table 1). However, theincidence among patients with up tofour TACE sessions and those with five or more sessions wasnot significantly different (p= 0.30). The chance of bileduct injury was significantly higher (p=0.01) after subsegmentalor segmental TACE than after lobar or more proximalTACE (Table 1).
final diagnosis of the treated tumor • The highincidence of bile duct injury in non-hepatocellular carcinomapatients also implies that the selective TACE, in the otherwisenormal liver, may occlude the nonhypertrophiedperibiliary plexus and result in ischemic injury.
incidence of TACE-induced bile duct is different • In the present study, 31 (11.3%) out of 274 patientsshowed TACE-induced bile duct injuries, an incidence muchhigher than in previous reports based on CT evidence but comparable with an autopsy series(12.5%). • differences in the patient populationand the TACE technique(The patient populations in previous reports were limited to patients with hepatocellular carcinomasarising in cirrhotic livers and highly selective embolization of the noncirrhotic liver.
highly selective embolization • The synergistic effect ofhighly selective embolization of the noncirrhotic liver wouldincrease the chance of ischemic bile duct injuries due tocomplete cessation of blood flow in the capillaries regardlessof the total volume of iodized oil injected into the tumorfeeder in each patient. • In other words, cirrhotic changes ofthe liver parenchyma and selectivity of the catheter tip duringthe TACE are more important than the total volume ofthe injected iodized oil.
In the presentstudy, despite the absence of statistical validation, the percentageof TACE-induced bile duct injury was higher inpatients with additional gelatin sponge embolization.
portal vein thrombosis • There was no significantfunctional impairment after TACE in our patients withportal vein thrombosis. it did not influence the incidence of bileduct injuries in our study. • In patients with portal vein thrombosis ,a compensatory increase of hepatic arterial flow wouldinduce hypertrophy of the peribiliary plexus.therefore, portal vein thrombosis may not be apredisposing factor to bile duct injury.
The number of repeated TACE • The number of repeated TACE procedures is one of thewell-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 patientswith repeated TACE due to the other predisposingfactors.
Conclusion • the chance of bile duct injury after TACEis increased in the noncirrhotic liver with a good liverfunction by selective embolization of distal arterial branches. • While not statistically significant, the additional use of gelatinsponge fragments, and the repeated number of TACEs, are alsobelieved to potentially exacerbate ischemic bile duct injury. • A prospective study of TACE-induced bile duct injury isneeded to establish other possiblefactors predisposing tobile duct ischemia.
