Fatal Bile Duct Necrosis: A Rare Complication of Transcatheter Arterial Chemoembolization in a Patient with Endocrine Hepatic Metastasis

We report the first case of fatal bile duct necrosis following transcatheter arterial chemoembolization (TACE) in a 58-year-old woman. The patient underwent two TACEs to treat hepatic metastases from an ileal endocrine tumor. Persistent cholestasis occurred after the second procedure, leading to the diagnosis of bile duct necrosis confirmed by liver biopsy. The patient died of liver failure with encephalopathy six months after the second TACE. Even though this complication is very rare, physicians should consider this diagnosis in patients who develop chronic, marked cholestasis following a TACE procedure

Hepatic proliferation and angiogenesis markers are increased after portal deprivation in rats: a study of molecular, histological and radiological changes.

To determine the pathogenesis of liver nodules, and lesions similar to obliterative portal venopathy, observed after portosystemic shunts or portal vein thrombosis in humans.We conducted an experimental study comparing portacaval shunt (PCS), total portal vein ligation (PVL), and sham (S) operated rats. Each group were either sacrificed at 6 weeks (early) or 6 months (late). Arterial liver perfusion was studied in vivo using CT, and histopathological changes were noted. Liver mRNA levels were quantified by RT-QPCR for markers of inflammation (Il10, Tnfa), proliferation (Il6st, Mki67, Hgf, Hnf4a), angiogenesis: (Vegfa, Vegfr 1, 2 and 3; Pgf), oxidative stress (Nos2, and 3, Hif1a), and fibrosis (Tgfb). PCS and PVL were compared to the S group.Periportal fibrosis and arterial proliferation was observed in late PCS and PVL groups. CT imaging demonstrated increased arterial liver perfusion in the PCS group. RT-QPCR showed increased inflammatory markers in PCS and PVL early groups. Tnfa and Il10 were increased in PCS and PVL late groups respectively. All proliferative markers increased in the PCS, and Hnf4a in the PVL early groups. Mki67 and Hnf4a were increased in the PCS late group. Nos3 was increased in the early and late PCS groups, and Hif1a was decreased in the PVL groups. Markers of angiogenesis were all increased in the early PCS group, and Vegfr3 and Pgf in the late PCS group. Only Vegfr3 was increased in the PVL groups. Tgf was increased in the PCS groups.Portal deprivation in rats induces a sustained increase in intrahepatic markers of inflammation, angiogenesis, proliferation, and fibrosis

Results of mRNA quantification by RT-QPCR.

<div><p>Aligned dot plots with bars at median for the expression of inflammatory (<i>Tnfa</i>, <i>Il10</i>), proliferative (<i>Hgf</i>, <i>Il6st</i>, <i>Mki67</i>, <i>Wnt2</i>, <i>Hnf4a</i>), Oxidative stress (<i>Nos2&3</i>), angiogenetics (<i>Vegfa</i>, <i>Flt1/VEGFR-1</i>, <i>Kdr/Vegfr2</i>,<i>Flt4/Vegfr3</i>), and fibrotic (<i>Tgfb</i>) mRNA markers by RT-QPCR according to the Delta-Delta Method (Sham = 1) at 6 weeks and 6 months.</p> <p>PCS: Portacaval shunt.</p> <p>PVL Portal vein ligation.</p> <p>S: Sham.</p> <p>*: significant difference.</p></div

Results of imaging evaluation of the three experimental groups.

<div><p>Aligned dot plots with bar at median for the expression of hepatic arterial fraction,blood perfusion, and total blood flow at 6 weeks and 6 months. Hepatic arterial fraction is significantly increased in the rats with portacaval shunts. At 6 weeks and 6 months, and total blood flow is decreased in both PCS and PVL at6 months compared to Shams.</p> <p>PCS: Portacaval shunt.</p> <p>PVL: Portal vein ligation.</p> <p>S: Sham.</p> <p>*: significant difference.</p></div

Gene, protein and the corresponding primers used for RT-QPCR studies.

<p>Gene, protein and the corresponding primers used for RT-QPCR studies.</p

Western blot of <i>Hif1a</i> protein in the liver at 6 weeks (6W) and 6 Months (6M) in Sham (S), Portacaval shunt (PCS), and Portal vein Ligation (PVL) rats.

<p>Nuclear (NUCL) and cytoplasmic (CYT) protein were fractioned and assayed for Histon 3 to serve as a nuclear marker and Actin to serve as a protein marker. There is no staining for Hif1a in each 6 weeks and 6 months groups.</p

Methods for Perfusion CT scan.

<p>Perfusion CT scan (left) and time-density curves of vascular ROIs after contrast material injection (right). A: sham group; B: portocaval shunt; C: portal vein ligation. Note the portal cavernoma on rats with total portal vein ligation (Green arrow).</p

Distribution of the remaining rats, available for experiments between PCS, PVL, and S groups in early and late sub-groups.

<p>Distribution of the remaining rats, available for experiments between PCS, PVL, and S groups in early and late sub-groups.</p