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Ischemic b ile d uct i njury as a s erious c omplication a fter TACE in p atients with HCC. Kim, Hae Kyung Korea J C linical G astroenterology 2001. Introduction.
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Ischemic bile duct injury as a serious complication after TACE in patientswith HCC Kim, Hae Kyung Korea J Clinical Gastroenterology 2001
Introduction • TACE has been widely used as an effective palliative treatment modality for patients with unresectable HCC. • Bile duct injuries also have beenreported, the exact incidence, pathogenesis, and clinicalsignificance remain to be clarified.
Aim • In this study, we evaluated the frequencies, patterns, and clinical implications ofischemic bile duct injuries after TACE in patients withHCC. • We also attempted to determine thepredisposing factors and possible pathogenic mechanisms and suggest measures to prevent these serious complications.
Materials • We retrospectively analyzed the medical records and radiologicfindings of 950 consecutive patients with HCC who had beentreated with TACE(807) or TACI(143).
TACE Methods • 10 mL of iodized oilmixed with cisplatin was injected via catheter,the tip of which was advanced into the proper hepaticartery. • This was followed by selective embolization of the feeding artery with gelatin sponge particles.( 5F 75-cm Rosch hepatic catheter and a microferret-18-infusion catheter).
TACI Methods • The remaining143 patients with main portal vein thrombosis were treated withTACI, which consists of the infusion of cisplatin alone withoutembolization.
Follow-up • Serum biochemistry, AFP, and CT were examined serially before and 4weeks after every treatment. • TACE wasrepeated every 12 weeks • TACI was repeated at 4-week intervals.
Result • 17 (2.1%) of the 807 patients treated with TACE developed biliary complications with no evidence of direct invasion of HCC. • Of the 17 patients: 14 were male and the mean age was 57 years. • Clinical characteristics of 17 patients are presented in Table 1.
Type of complication • Mild diffuse dilatations of the IHD :2 • The diffuse IHD dilatations were found incidentally on follow-up CT and required no treatment. • Focal strictures of CHD or CBD with marked secondary dilatation of the IHD: 3 • Subcapsular bilomas :12(averaged 6.8 cm in size)
Treatment of complication • All 3 patientswith focal strictures and 4 withbilomas had associated bacterial infections at presentation,which required urgent drainage procedures . • 2 patients with focal strictures of thelarge bile ducts required surgical management despite adrainage procedure. (a right lobectomy with hepaticojejunostomy).
Pathogenicmechanisms • The tissue showed a thick fibrous band at the stricture site of the CHD; • Epithelialcells of the bile duct weredenuded and the stricture site wasassociated with extensive periductal fibrosis.
Results • The median numbers of TACE tended to be greater in the patients with focalstricture than in those with bilomas (6.0 vs. 2.5; p=0.08). • None of 143 patients with HCC treated with TACI developed any ischemic biliary injury.
Discussion • We observed various patterns of bile duct changes afterTACE, which wecategorized as three types: biloma, focalstricture of large bile ducts, and diffusedilatation of IHD.
Serious biliary infections • Focal strictures of large bile ducts after ischemic injuriesare more likely to be associated with serious biliary infections than other patterns of biliary changes located in theperipheral bile ducts.
Post reported mechanisms • Gelfoam, lipiodol, cisplatin, or mechanicalvascular injuries during the procedure could induce the injuries. • Sclerosing cholangitis after treatment with hepatic arterial floxuridinechemotherapy. • In our study , cisplatin mayhave no effect on the development of biliary injury afterTACI.
Lipiodolhas been known to occlude such small peripheral vessels, especially at the level of peribiliary capillaryplexus. • Gelfoam can obliterate the larger andmore proximal feeding arteries of tumors.
Biloma formation • Biloma is an encapsulated collection of bile, which has been sealed off by the adhesive epithelialization process, resulting from direct injury to the biliary tree.
Mechanisms of biloma • Biloma induced after TACE seems tobe a consequence of occlusion of smallperipheral hepaticarteries with lipiodol, followed by bile duct epithelial necrosis. • Ischemic injury to such peripheral intrahepatic ducts seems tocause the leak of bile and formation of bile cysts.
Focal strictures formation • Focal strictures of large bile ducts seem to bethe result of repeated ischemia for prolonged periods byembolization with Gelfoam.There are two reason:
Reasons of focal strictures • ①Gelfoam can obliterate the larger andmore proximal feeding arteries of tumors, whereas lipiodol embolize only peripheral arterialbranches. • ②We have demonstrated that thepathologic features of a narrowed bile duct after repeatedTACE using Gelfoam were intense fibrosis and granulationtissue associated with denudation of epithelial layer.
Mechanisms of focal strictures • Thus, we speculated that repeated embolization with Gelfoam resulted in ischemic arteritis, followed by the chronic inflammation of large bile ducts,which eventually lead to focal extensive fibrosis.
The number of TACE • The number of TACE was greater in patients with focalstricture than in those with biloma. • This finding suggeststhat repeated direct mechanical injuries to vessel wallscaused by the catheter might play some role in the pathogenesis of focal strictures of the large bile duct.
Indication • When patients with HCC treated with TACE manifestprogressive obstructive jaundice while the tumors are stableor in remission. • one should suspect ischemic bile duct injuries, especially focal stricture of large ducts.
Prevention • The catheter should be inserted more selectively intothe peripheral arteries; • It is also necessary to perform theprocedure carefully, considering the amount and the size ofGelfoam particles and the individual characteristics of vascular anatomy.
Conclusion • Ischemic bile duct injuries were not uncommon in patients with HCC treated with TACE. • Bilomaseems to be associated with ischemic injuries of small bileducts that are probably caused by lipiodol rather than Gelfoam, • In contrast to focal strictures of large bileducts after repeated ischemia for prolonged periods by embolization with Gelfoam.
Suggestion • We suggest that most of the focalstrictures of large bile ducts andbilomas maybe complicated with serious biliary infections, which necessitate urgent biliary drainage procedures.
Suggestion • We also suggestthat adjustments in the amounts of lipiodol or Gelfoam andin the sites of embolization may reduce the risk of ischemicbiliary injuries after TACE in patients with HCC.