Trial Information

Sequential Preoperative Ipsilateral Hepatic Vein Embolization After Portal Vein Embolization to Induce Further Liver Regeneration in Patients With Hepatobiliary Malignancy

To prospectively assess the effect of ipsilateral HVE after PVE on liver volume change, this
study was designed to continue for 12 months, from March 2007 to February 2008.

This study protocol was approved by our institutional review board, under the condition
that, for patient safety, more than one occurrence of accidental coil migration into the
heart or lung would lead to study discontinuation. The clinical significance of this risk
had not been fully assessed, although it might not be seriously harmful. In addition,
informed consent and permission for each PVE and HVE were obtained separately from each
patient and/or his/her family members.

The indications for right PVE are patients undergoing right hepatectomy or more extensive
liver surgery for hepatobiliary malignancy, but having small FLRs, with mean values less
than 40% of total liver volume. Patients with large liver masses are excluded because their
parenchymal resection rates were much lower than 60%. For patients with perihilar
cholangiocarcinoma, placement of multiple biliary drains was preferred to decompress the
entire biliary system, and the timing of PVE was set to when serum total bilirubin level
became lower than 5 mg/dL.

The right internal jugular vein was punctured with an 18-gauge needle and a 9-F long sheath
(Cook; Bloomington, IN) was inserted. The right hepatic vein (RHV) was selected using a 5-F
cobra catheter (Cook) and a 0.035-inch guide wire (Terumo; Tokyo, Japan). Insertion of the
guide wire toward the dorsal side was checked with a right lateral view to confirm that it
was correctly inserted into the RHV. A 9-F sheath was inserted at the proximal portion of
the RHV, followed by placement of a Tulip filter (retrievable vena cava filter; Cook) or a
Trap-Ease filter (Cordis; Miami, FL) to prevent migration of deployed coils during
embolization of the RHV. The cobra catheter was then advanced into the RHV and the main RHV
branches were embolized with coils 8 to 12 mm in diameter (nester embolization coils; Cook).

Multidetector dynamic CT scans were routinely performed before PVE to assess gross liver
volume change and tumor progression, and CT scans were performed every week after PVE, HVE,
and hepatectomy. All CT images were reconstructed as sections 3 mm thick. The CT images were
stored in a Picture Archiving and Communication System (PACS; Petavision; Asan Medical
Center, Seoul, Korea), enabling image processing and various measurements including
volumetry. In patients undergoing combined caudate resection, the volume of the caudate lobe
was not included in the FLR volume. TLV and FLR volume before PVE were used as the baseline
liver volumes for liver size comparison.

To assess the histological changes in the livers, 1 cm-sized pieces of liver tissue were
excised from the ventral margins of the right posterior section, right anterior section, and
left lateral section just after laparotomy. These samples were immediately fixed with 4%
paraformaldehyde phosphate solution.

Immunohistochemical stainings were performed using antibody against albumin to assess the
synthetic function of the hepatocytes, antibody against proliferating cell nuclear antigen
(anti-PCNA) to assess cell replication, and antibody against cleaved caspase-3 to assess
apoptosis. Apoptosis was also assayed by terminal deoxynucleotidyl transferase-mediated
dUTP-digoxigenin nick-end labeling (TUNEL) staining. Western blots using antibodies against
the acute phase proteins TNF-α, caspase-3, Bax, and Bcl-2 were performed to assess the
status of proinflammatory cytokine responses. PCNA-positive and caspase-3-positive events
were counted in five randomly selected high-power fields on microphotographs.

Specimens for histological examination and histomorphometric analysis were stained with
hematoxylin and eosin (H-E). For hepatocyte counts, 10 different HPFs in the same slide were
randomly selected.