Satoshi Kobayashi, Japan

AJG,1993

Postmortem survey of bile duct necrosis and

biloma in hepatocellular carcinoma after tran

scatheter arterial chemoembolization therap

y: relevance to microvascular damages of p

eribiliary capillary plexus

Purpose

①determining the incidence of bile duct necrosis and biloma in HCC after transcatheter arterial embolization therapy (TAE) or hepatic arterial infusion chemotherapy (HAI).

②clarifying the relationship between these duct injuries and the peribiliary capillary plexus (PBP).

Introduction

• The liver is dually supplied by hepatic arterial and portal venous blood, whereas HCC is mainly supplied by the former;

• The biliary tree is supplied primarily by hepatic arterial branches which give off a vascular plexus around the bile ducts ( PBP).

Meterials and Methods

• The control group (48): ①HCC+history+cirrhosis, ②HCC+cirrhosis, ③cirrhosis, ④nomal liver ;

• The test group(56): HCC+historry+cirrhosis. (hisstorry=TAE or HAI).

• Both of the two groups collected more than 5 liver specimens.

• In the test and control groups with a history of TAE, gelfoam added by lipiodol and anticancer drugs was used as the embolus (chemo-embolization).

Tissues process

• All of these specimens were fixed in 10% neutral formalin and embedded in paraffin. More than 20 serial sections, 5 um thick, were cut, and some of them were processed for routine stainings including (H&E) and Mallory's azan. The rest were used for the endothelial stainings (immunohistochemistry).

Classification of intrahepatic biliary tree

The intrahepatic biliary tree was divided into bil

e ductules, interlobular bile ducts（ 20-80u

m） , septal bile ducts（＞ 80um） ,and lar

ge bile ducts.

Classification of PBP

Around the septal and large bile ducts, there are small vessels regularly arranged just beneath the bile duct epithelium (inner layer of PBP) and those in the periductal tissue (outer layer of PBP)(Fig. 1).

The numerical changes of the inner layer vessels of PBP were evaluated semiquantitatively in comparison to normal counterparts. That is, the bile ducts were graded into three groups: ①no or mild reduction,②moderate reduction, ③marked reduction.

Fig.1

Survey of bile duct necrosis and biloma in autopsy livers

• Bile duct necrosis and biloma were grossly surveyed in the 104 consecutive autopsy livers of HCC from 1982 to 1992 in our laboratory (male=81 , female=23 ; mean age=62.7 yr).

• All of these cases were complicated by cirrhosis.

The definition of bile duct necrosis and biloma

• bile duct necrosis was defined as coagulation necrosis of bile duct with or without the adjacent portal elements imbibed deeply by bile, and grossly appeared as a loose tissue deeply imbibed by bile and contained vague outlines of bile ducts and other elements of portal tracts. (Figs. 2 and 3)

• Biloma was defmed as a round,softened lesion with bile imbibition .

Figs. 2 and 3

Statistics

• The incidence of bile duct injuries and the degree of reduction ofthe PBP vessels were examined by Fisher's exact probability test and by Wilcoxon's rank sum test;

• P values < 0.05 were considered significant.

Results

• Among the 104 autopsy cases of HCC, 56 cases had a history of TAE and/or HAI. Bile duct necrosis had 7 cases (12.5%) of the 56 cases, but was not found in the remaining 48 cases without such history (p < 0.02).

• Main clinicopathological fmdings of these 7 cases are shown in Table 1.

Table 1

Pathologic changes

• Histometric study disclosed that the diameter of the affected bile ducts was more than 200 um.

• Within these necrotic bile ducts, the inner and outer layer vessels of PBP were lost or showed coagulation necrosis (Fig. 4). Bile duct epithelium adjacent to the necrosis showed variable regenerative and regressive changes.

• Some arteries which were variably involved in the necrotic process of bile duct necrosis showed coagulation necrosis and thrombosis (Fig. 4).

Fig. 4

Histology of the PBP

• The inner layer vessels were markedly reduced in the livers with a history of TAE or HAI (Figs. 5 and Figs.6), whereas the number of outer layer vessels was not constant.

• In the cases of HCC with TAE or HAI therapy and bile duct necrosis and/or biloma, about one-half of the nonnecrotic bile ducts in the vicinity of the necrotic bile ducts showed marked reduction of the inner layer vessels (Fig. 6).

Figs. 5 and Figs.6

Statistical results

• The degree of reduction in the inner layer vessels of PBP in individual cases is shown in Table 2.

Table 2

Discussion

• The present study discovered :bile duct necrosis or biloma in cirrhotic livers with HCC was exclusively found in the patients with a history of HAI or TAE(12.5%).It is of interest that such complications were not detected or suspected antemortem in these cases.

• These injuries selectively affected the septal and large bile ducts in which the PBP is well organized into the inner and outer layers. Therefore, the possibility that this two-layer pattern is constitutively related to the occurrence of these complications was examined in this study.

The inner layers of PBP around the septal and large bile ducts were preserved in cirrhotic livers or without a history of TAE in HCC.

Marked reduction of the inner layer vessels might be due to TAE or HAI, thus the inner layer of PBP may have been damaged during these therapies (gelfoam, lipiodol, or anticancer drugs? —remains unsettled ).

• Arterial necrosis found in the border of bile duct necrosis is due to contiguous extension of necrotic process of bile ducts.

• Tears or necrosis of biliary epithelial layer due to unidentified causes during or after these therapies may be responsible for leakage of corrosive bile juice.

• Chemical toxicity of anticancer drugs added to TAE or used in HAI may be related to the initiation of biliary.

Conclusion

• These microvascular injuries seem necessary but were insufficient for the induction of these biliary injuries, because the inner layer vessels were also markedly reduced in the HCC cases with a history of TAE, but with no such injuries.

Thank you for your attention