Journal of Gastroenterology and Hepatology (2000) 15, 346348

prevent pulmonary infarction and/or to ameliorate TT-

related symptoms, such as oedema and ascites.
10,11
However, the effects of such a surgical procedure will
be transient and limited, unless new extension of the
TT is prevented by successive treatments for hepatic
tumours. Liver transplantation is another surgical treat-
ment for HCC, but the unfavourable outcomes
reported in advanced HCC do not encourage liver
transplantation for patients with HV-TT, given the
serious shortage of donor organs.
12
The prognosis of patients after these surgical treat-
ments is generally poor, even when hepatic resection
with removal of TT is successfully performed.
911
The
prognosis of such resected patients has been reported
to depend on the extension of TT through the HV
and/or coexistence of portal vein TT (PV-TT).
13,14
Patients with HV-TT alone show a better prognosis
than those with TT extending into the IVC; the
outcome of patients with IVC-TT is extremely poor
because of early distant-organ metastasis.
13
The prog-
nosis of patients with HV-TT can also differ consider-
ably, depending on whether they have TT in the PV; the
prognosis of patients with TT in both the PV and HV
is much poorer, probably because they are also at high
risk for intrahepatic metastasis through PV-TT.
14
Most patients with HV-TT are not treated surgically
because of concomitant liver dysfunction, but receive
non-surgical treatment. In some patients, only palliative
treatments may be offered due to the advanced stage of
HCC in the liver. Non-surgical treatments include tran-
scatheter arterial embolization (TAE), chemotherapy,
and radiation therapy. Successful non-surgical treat-
ments may allow a small subset of patients with initially
unresectable HCC to become candidates for surgical
treatment.
15
Moreover, given marked tumour regres-
sion, the surgical procedure required for radical resec-
tion may become less invasive. However, at present,
little anti-tumour effects can be expected from any non-
surgical treatments in patients with HV-TT.
See article in J. Gastroenterol. Hepatol. 1999; 14: 9227.
Recently, screening of high-risk populations for hepa-
tocellular carcinoma (HCC) by using ultrasonography
and serum alpha-fetoprotein levels has facilitated the
early detection of HCC. However, at the time of diag-
nosis, some HCC patients still have advanced disease
with hepatic vein tumour thrombus (HV-TT). Hepato-
cellular carcinoma has a tendency to involve vascular
structures in the liver, such as the portal veins (PV) and
the hepatic veins (HV). Although HCC involvement of
the HV is less frequently observed compared with that
of the PV, tumour thrombus (TT) extending into the
inferior vena cava (IVC) and right atrium (RA) through
the HV has been encountered.
1
Despite the progress of
therapy for HCC, HCC patients with HV-TT generally
have an extremely poor prognosis.
A certain number of patients with HV-TT may
develop secondary BuddChiari syndrome, pulmonary
infarction, and/or lung metastasis, especially when TT
extend into the IVC.
2
Further extension of HCC into
the RA can cause cardiac failure and ball valve throm-
bus syndrome.
3
Because of the advances in imaging
modalities, tumour growth through the HV can be diag-
nosed with certainty. On angiography, the threads and
streaks sign, indicating feeder vessels of the TT, may be
observed from the HV to the IVC and the RA.
4
In
recent years, ultrasonography and computed tomogra-
phy have become the most useful and most commonly
used modalities for the diagnosis of HV-TT.
5
Magnetic
resonance imaging may offer further detailed informa-
tion on TT, such as the presence of vascular lumens
between the TT and IVC wall.
6
In HCC patients with HV-TT, hepatic resection with
removal of the TT is the only radical treatment that may
facilitate prolonged survival, although such extensive
surgery is applied only to patients with sufcient hepatic
reserve to tolerate surgery.
79
Tumour thrombus
removal without hepatic resection is also carried out to
EDITORIAL
How to manage hepatic vein tumour thrombus in
hepatocellular carcinoma
SHUICHI OKADA
Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
Correspondence: Dr S Okada, Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1
Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Email: sokada@ncc.go.jp
Accepted for publication 12 October 1999.
2000 Blackwell Science Asia Pty Ltd
Management of hepatic vein thrombus in HCC 347
Transcatheter arterial embolization, either alone or in
combination with intra-arterial chemotherapy, has a
marked anti-tumour effect against HCC because this
neoplasm receives its blood supply through the hepatic
artery.
16,17
The effect of TAE is dependent on the growth
pattern of HCC; the effect is more apparent in nodular
lesions, while inltrative HCC does not respond as well
as nodular HCC.
18
The anticancer effect of TAE in
HCC patients with HV-TT is usually limited, although
HV-TT is also fed from tumour vessels derived from
the hepatic artery. The possible reason for this refrac-
toriness of HV-TT to TAE is that most such cases show
an inltrative growth pattern macroscopically.
19
Seg-
mental TAE, which has recently been reported to show
a marked anti-tumour effect against PV-TT, should also
be evaluated in patients with HV-TT, as it can enhance
the anti-tumour effect and can be performed more
safely than conventional TAE.
2022
Chemotherapy for HCC, either systemically or intra-
arterially, has been of limited value in clinical practice,
because only a small portion of patients will obtain
meaningful palliation.
6,2327
In particular, patients with
quite advanced HCC are inappropriate candidates for
systemic chemotherapy, because the disease is more
refractory to chemotherapy at that stage.
28
However,
hepatic intra-arterial infusion (HAI) may have to be
tested in patients with HV-TT, as HAI has been
reported to show promising results in HCC patients
with TT in the main portal branch.
29
Radiation therapy
may be a good palliative therapy, either alone or in
combination with other treatments for HCC with TT
extending through the HV; radiation therapy for TT
may induce tumour regression, resulting in palliation of
TT-related symptoms.
3032
This is the background to the paper by Kashima et al.
published in a recent issue of the Journal of Gastroen-
terology and Hepatology.
33
They treated ve patients with
advanced HCC showing extensive tumour growth
through the HV by HAI by using aclarubicin, mito-
mycin C and lipiodol. Although two patients died of
cancer within several weeks after HAI, the remaining
three demonstrated remarkable tumour regression. As
a result, two of these three patients could undergo
potentially curative resection, and surgical specimens
revealed coagulation necrosis (complete necrosis in one,
and partial in one) in both the hepatic tumours and the
TT. Furthermore, the prognoses of the three patients
were incredibly improved, even though all patients had
TT in the IVC and/or the PV. Kashima et al. concluded
that HAI using these agents might be an effective treat-
ment for HCC with extensive tumour growth through
the HV.
However, several cautions are necessary in interpret-
ing the results by Kashima et al. First, the number of
patients enrolled in this trial was too small to accurately
evaluate the anti-tumour and adverse effects of HAI.
Moreover, according to intention-to-treat analysis,
these effects must be evaluated in all patients who
receive the therapy. Second, patient selection for HAI,
which was not described in detail in the paper, must
be optimized to achieve the potential benets of HAI
without inducing severe complications. The two
patients with early death after treatment might not have
been appropriate candidates for this therapy. Finally,
the HAI method somewhat varied with each patient, in
terms of the combined use of gelatin powder and mit-
omycin C. To dene the real role of this HAI in patients
with HV-TT, further trials, which include a large
number of patients, are mandatory.
Among HCC patients with HV-TT, disease status
(extension of TT and associated liver disease) varies
greatly with each patient. For patients who have less
advanced tumour stage and better liver function, surgi-
cal treatment is the treatment of choice. In particular,
patients with HV-TT alone may be the optimal candi-
dates for surgical treatment; HV-TT can be removed by
anatomical hepatic resection, and longer survival can be
expected with the removal of both the hepatic tumours
and HV-TT. In contrast, when TT extends into the
IVC, and/or PV-TT coexists with HV-TT, the indica-
tion for such surgical treatment should be considered
prudently. In these patients, a more drastic surgical pro-
cedure is required, and its effect on prognosis remains
to be elucidated.
13,14
However, surgical removal of TT
in the IVC and RA may be indicated only when hepatic
tumours are under control or will be effectively con-
trolled by non-surgical treatments.
Patients who are unsuitable for resection may be
enrolled in phase II trials to evaluate the anti-tumour
effect and toxicity of various non-surgical treatments,
if they are expected to be able tolerate treatment.
Although none of the non-surgical treatments currently
shows reliable anti-tumour effects in patients with HV-
TT, TAE may be the most promising method of achiev-
ing signicant tumour necrosis. However, for patients
with TT in the main portal branch or poor hepatic
reserve (Childs grade C), TAE is not applicable. Such
patients may undergo chemotherapy, especially HAI,
in a clinical trial. Radiation therapy for TT may also
be performed either alone or in combination with other
non-surgical treatments to palliate TT-related symp-
toms. In addition, patients in this unresectable group
who request treatment may be treated with more exper-
imental therapies in a phase I setting.
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