AJR 2000; 175:1673-1675
© American Roentgen Ray Society
Intrahepatic Metastasis in Hepatocellular Carcinoma Through Reversed Hepatic Venous Flow
Su Kyung An1,
Jin Wook Chung1,
Tae Kyoung Kim1,
Hyun Beom Kim2,
Joon Koo Han1,
Byung Ihn Choi1 and
Jae Hyung Park1
1
Department of Radiology, Seoul National University College of Medicine and the
Institute of Radiation Medicine, SNUMRC, 28 Yongon-dong, Chongno-Gu, Seoul,
110-744, Korea.
2
Department of Radiology, Hallym University Sacred Heart Hospital, 896
Pyungchon-dong, Anyang-city, Kyungki-do, 431-070, Korea.
Received February 24, 2000;
accepted after revision May 15, 2000.
Address correspondence to J. W. Chung.
Introduction
Hepatocellular carcinoma frequently manifests as multiple lesions in the
liver. The multiplicity of the lesions has been explained by a multicentric
origin of hepatocellular carcinoma
[1] and intrahepatic spread
through the portal vein [2]. We
present a case of hepatocellular carcinoma with an unusual pathway of
intrahepatic metastasis: retrograde seeding through the hepatic
vein.
Case Report
A 59-year-old man visited our hospital with a chief complaint of dark
yellowish urine. Physical examination revealed atrophic skin and
telangiectasia on the face and neck. Laboratory tests disclosed the following
abnormalities: serum aspartate aminotransferase level of 510 U/L, serum
alanine aminotransferase level of 1228 U/L, and positive serologic test for
hepatitis-B surface antigen. The serum level of 
-fetoprotein was 37
ng/mL. Contrast-enhanced helical CT revealed a 6-cm mass in the anterior
superior segment of the right lobe of the liver without evidence of venous
invasion. Percutaneous needle biopsy confirmed the diagnosis of hepatocellular
carcinoma. The patient was referred to our department for transcatheter
arterial chemoembolization.
On celiac arteriography, a hypervascular mass was present in the right lobe
of the liver that is supplied by the anterior superior segmental branch of the
right hepatic artery (Fig. 1A). A mixture of an iodized oil (Lipiodol; Andre Guerbet, Aulnay-sous-Bois,
France) and doxorubicin hydrochloride (ADM; Dong-a Pharmacy, Seoul, Korea) was
infused through the feeding artery followed by embolization with absorbable
gelatin sponge particles (Gelfoam; Upjohn, Kalamazoo, MI). After three
sessions of chemoembolization through the same feeding artery for 5 months, no
radiologic evidence of tumor vascularity was visible on hepatic arteriography
(Fig. 1B) or contrast-enhanced
helical CT. The serum level of -fetoprotein also decreased below 5
ng/mL. On follow-up hepatic arteriography performed 9 months after the last
treatment, marginal tumor recurrence was detected
(Fig. 1C)
. At that time, the
portal and hepatic veins were widely patent, and no evidence of arteriovenous
shunt was seen on CT or angiography. The patient was treated with three
additional sessions of chemoembolization through the right hepatic artery and
four sessions of percutaneous ethanol injection therapy. The serum level of
-fetoprotein continuously remained below 5 ng/mL.
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Fig. 1B. —Hepatocellular carcinoma in 59-year-old man. Celiac
arteriogram obtained after three sessions of transcatheter arterial
chemoembolization shows localized accumulation of iodized oil
(arrows) in tumor. Note no evidence of residual tumor
vascularity.
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Fig. 1C. —Hepatocellular carcinoma in 59-year-old man. Follow-up celiac
arteriogram obtained 9 months after last treatment shows marginal tumor
recurrence (arrows), but there was no evidence of hepatic vein
invasion and arteriovenous shunt.
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Fig. 1D. —Hepatocellular carcinoma in 59-year-old man. Celiac arteriogram obtained 10 months after further chemoembolization and percutaneous ethanol injection therapy for recurrent tumor (29 months after initial treatment) shows additional accumulation of iodized oil in recurrent tumor and no residual tumor vascularity (arrows).
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Four years after the initial treatment, contrast-enhanced helical CT showed
an enhancing mass along the middle hepatic vein
(Fig. 1E). Hepatic
arteriography revealed tumor thrombi with a typical appearance in a branch of
the middle hepatic vein (Fig.
1F), and these thrombi extended into the main trunk of the middle
hepatic vein. There was retrograde opacification of the peripheral branches of
the middle hepatic vein and the corresponding liver parenchyma due to
arteriohepatic venous shunt associated with tumor thrombi
(Fig. 1F). No evidence of
portal venous invasion of hepatocellular carcinoma could be seen on
angiography or CT. Chemoembolization was performed at the right anterior
segmental branch and the left medial segmental branch of the hepatic artery.
On follow-up hepatic arteriography and CT performed 7 months later, multiple
small nodular tumors developed in the area exactly matching the territory of
the middle hepatic vein opacified through the arteriohepatic venous shunt
(Figs. 1G and
1H). In spite of repeated
chemoembolization, the patient died of variceal bleeding 5 months after the
last imaging study.
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Fig. 1E. —Hepatocellular carcinoma in 59-year-old man.
Contrast-enhanced helical CT scan obtained 4 years after initial treatment,
which included seven sessions of transcatheter arterial chemoembolization and
four sessions of percutaneous ethanol injection therapy, shows enhancing mass
along middle hepatic vein (arrows).
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Fig. 1F. —Hepatocellular carcinoma in 59-year-old man. Early phase of
celiac arteriogram obtained 1 month after E shows tumor thrombi in middle
hepatic vein with "thread and streaks" appearance (solid
arrows). Note retrograde opacification of peripheral branches of middle
hepatic vein and corresponding liver parenchyma through arteriohepatic venous
shunt (open arrows).
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Fig. 1G. —Hepatocellular carcinoma in 59-year-old man. Follow-up
hepatic arteriogram (G) and CT scan (H) obtained 7 months after
F show multiple small nodular tumors in area matching territory of
middle hepatic vein opacified by arteriohepatic venous shunt.
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Fig. 1H. —Hepatocellular carcinoma in 59-year-old man. Follow-up
hepatic arteriogram (G) and CT scan (H) obtained 7 months after
F show multiple small nodular tumors in area matching territory of
middle hepatic vein opacified by arteriohepatic venous shunt.
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Discussion
Hepatocellular carcinomas manifested as multiple nodules in the liver have
been regarded as multicentric in origin or intrahepatic metastases through the
portal vein. Mitsunobu et al.
[3] provided strong supporting
evidence of intrahepatic metastases of hepatocellular carcinoma through the
portal vein in a study of 231 liver specimens of resected hepatocellular
carcinomas. Strong statistical correlation was seen between the presence of
intrahepatic metastasis and the frequency of vascular invasion. Direct
injection of radiopaque material into 23 resected tumors and percutaneous
injection in eight unresectable lesions revealed that the portal vein might
act as an efferent vessel of tumor. Moreover, macroscopic tumor thrombi were
found in the portal vein in 16.4% of the patients.
The frequency of hepatic vein invasion in hepatocellular carcinoma is much
lower than that of portal vein invasion. A retrospective study by Mathieu et
al. [4] of 134 patients with
hepatocellular carcinoma revealed hepatic venous involvement in 5.9% of the
patients. Okuda et al. [5]
reported angiographic visualization of tumor growth in the hepatic vein in
nine (6.3%) of 141 patients. Whereas portal venous thrombi are stacked in the
peripheral branches of the portal vein, small tumor thrombi in the hepatic
vein might be washed into the systemic circulation by continuous hepatofugal
flow at its early stage, increasing the chance of extrahepatic metastasis
[6]. Therefore, if the vein is
patent, it is unlikely that intrahepatic metastases through the hepatic vein
can occur. However, if the tumor thrombus in the hepatic vein occludes hepatic
venous outflow, the flow direction of the occluded hepatic vein may reverse,
and intrahepatic metastases of the tumor through the hepatic vein may
occur.
In the present case, tumor thrombi in the middle hepatic vein occluded its
main trunk, and the associated arteriohepatic venous shunt resulted in
reversal of the flow direction of the occluded hepatic vein. This fact was
clearly shown by hepatic arteriography
(Fig. 1F). On 7-month follow-up
hepatic arteriography, tumor implantation in the territory of reversed hepatic
venous flow was proved angiographically
(Fig. 1G). Because there was no
evidence of portal vein invasion of the tumor and the area of tumor recurrence
was well matched with the area with reversed flow direction of the hepatic
vein, we believe that recurred tumors were metastasized through the hepatic
vein.
In conclusion, hepatic vein invasion and resultant hemodynamic alterations
should be considered as one of the causes of intrahepatic metastasis in
hepatocellular carcinoma.
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Introduction
Case Report
