Content uploaded by Kenichiro Okumura
Author content
All content in this area was uploaded by Kenichiro Okumura on Sep 23, 2018
Content may be subject to copyright.
CLINICAL INVESTIGATION
Comparison of Local Control in Transcatheter Arterial
Chemoembolization of Hepatocellular Carcinoma £6 cm With
or Without Intraprocedural Monitoring of the Embolized Area
Using Cone-Beam Computed Tomography
Shiro Miyayama •Masashi Yamashiro •Masahiro Hashimoto •
Nanako Hashimoto •Masaya Ikuno •Kenichiro Okumura •
Miki Yoshida •Osamu Matsui
Received: 14 March 2013 / Accepted: 12 May 2013
ÓSpringer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2013
Abstract
Purpose This study was designed to compare technical
success and local recurrence rates of transcatheter arterial
chemoembolization (TACE) for hepatocellular carcinoma
(HCC) with/without monitoring of embolized areas using
cone-beam computed tomography (CBCT).
Methods A total of 207 HCCs B6 cm were treated with
superselective TACE using digital subtraction angiography
(DSA) alone (DSA group, 98 tumors of 70 patients) or plus
CBCT monitoring (CBCT group, 109 tumors of 79
patients). Technical success of TACE was classified into
three grades according to 1-week CT; the tumor was
embolized with a safety margin (5-mm wide for tumors
\25 mm, and 10-mm wide for tumors 25Cand B60 mm;
grade A), without a margin in parts (grade B), or the entire
tumor was not embolized (grade C). Technical success and
local recurrence rates in the DSA and CBCT groups were
compared. Local recurrence rates of grade A and B tumors
were also compared.
Results The grade A/B/C tumors in the DSA and CBCT
groups were 64 (65.3 %)/25 (25.5 %)/9 (9.2 %) and 95
(87.2 %)/11 (10.1 %)/3 (2.8 %), respectively. Local
recurrence developed in 46/158 (29.1 %) grade A tumors
and 24/36 (66.7 %) grade B. There were significant dif-
ferences in technical success between the DSA and CBCT
groups (p\0.001) and local recurrence rates between
grade A and B tumors (p\0.001). The 1-, 2-, and 3-year
local recurrence rates in the DSA and CBCT groups were
33.3 and 22.3 %, 41.3 and 26.8 %, and 48 and 30.6 %,
respectively (p=0.0217).
Conclusion Intraprocedural CBCT monitoring of embol-
ized areas reduces the local tumor recurrence.
Keywords Hepatocellular carcinoma Transcatheter
arterial chemoembolization Monitoring of the embolized
area Cone-beam computed tomography Local recurrence
Introduction
The prognosis of patients with inoperable hepatocellular
carcinoma (HCC) has improved with advances in therapeutic
options such as local ablation therapies in addition to trans-
catheter arterial chemoembolization (TACE) [1–6]. Local
tumor control is important to prolong the life span of patients
with inoperable HCC [7]; therefore, advancement in TACE
technology may be directly connected with patient prognosis.
S. Miyayama (&)M. Yamashiro M. Hashimoto
N. Hashimoto M. Ikuno K. Okumura M. Yoshida
Department of Diagnostic Radiology, Fukuiken Saiseikai
Hospital, 7-1, Funabashi, Wadanaka-cho, Fukui 918-8503, Japan
e-mail: s-miyayama@fukui.saiseikai.or.jp
M. Yamashiro
e-mail: m-yamashiro@fukui.saiseikai.or.jp
M. Hashimoto
e-mail: mas-hashimoto@fukui.saiseikai.or.jp
N. Hashimoto
e-mail: na-hashimoto@fukui.saiseikai.or.jp
M. Ikuno
e-mail: m-ikuno@fukui.saiseikai.or.jp
K. Okumura
e-mail: o-kenichiro@fukui.saiseikai.or.jp
M. Yoshida
e-mail: mik-yoshida@fukui.saiseikai.or.jp
O. Matsui
Department of Radiology, Kanazawa University Graduate
School of Medical Science, 13-1, Takara-machi,
Kanazawa 920-8641, Japan
e-mail: matsuio@med.m.kanazawa-u.ac.jp
123
Cardiovasc Intervent Radiol
DOI 10.1007/s00270-013-0667-2
There are various TACE techniques, for example, the
use of different chemotherapeutic agents and embolic
materials, as well as different catheter positions and mag-
nitudes of embolization. In addition, a safety margin for the
treatment is also important to achieve complete tumor
remission [8]. It is reported that a combined computed
tomography (CT)-angiography system is useful not only
for detection of tumors but also for monitoring the em-
bolized area during TACE [4,5].
Cone-beam CT (CBCT) is a new technology to obtain
CT images using a C-arm angiography system equipped
with a flat panel detector (FPD) rotating around the patient.
Recently, this technology has been introduced into several
interventional procedures. CBCT has also been used in
TACE instead of conventional CT [8–15]; however, the
efficacy of CBCT for local tumor control is still uncertain.
Thus, the purpose of this study was to compare the tech-
nical success and local recurrence rates of TACE for HCC
B6 cm with or without intraprocedural monitoring of the
embolized area using CBCT.
Materials and Methods
Our institutional review board approved the use of proto-
type CBCT software (XperCT, Philips Healthcare, Best,
The Netherlands). The institutional review board also
approved this retrospective study, and no individual patient
consent was required. Written, informed consent was
obtained from each patient before the TACE procedure.
Patients
We defined superselective TACE as TACE performed at a
more distal level of the segmental artery of the hepatic artery.
In the present study, we selected newly developed HCC
lesions B6 cm that could be detected on digital subtraction
angiography (DSA) and treated with superselective TACE
alone. The diagnosis of HCC was made by imaging findings;
nodular staining and washout on dynamic CT and/or dynamic
magnetic resonance imaging (MRI), and nodular staining on
DSA and nodular perfusion defects on CT during arterial
portography (CTAP) using a conventional CT scanner or
CBCT. Between January 2004 and April 2006, 98 tumors in
70 patients were treated with superselective TACE using DSA
alone after CTAP that was performed in a CT room (DSA
group). Between January 2008 and December 2010, 109
tumors in 79 patients were treated with superselective TACE
using DSA plus intraprocedural monitoring of the embolized
area by CBCT with a 10.4-s scan and 512 9512 matrix
reconstruction (CBCT group). We excluded tumors for which
CBCT was performed during TACE but the embolized area
was not monitored with selective CBCT during hepatic
arteriography (CBCTHA) at the TACE point or CBCT
obtained immediately after injection of a mixture of iodized
oil (Lipiodol; Andre Guerbet, Aulnay-sous-Bois, France) and
anticancer agents (LipCBCT). We also excluded tumors that
were treated between June 2006 and May 2008 using CBCT
software with a 10.4- or 20-s acquisition and 256 9256
matrix reconstruction.
TACE Procedure
All TACE procedures were performed by using a micro-
catheter with a 2-F tip (Progreat a, Terumo Clinical Supply,
Kakamigahara, Japan) or a 1.8-F tip (Carnelian PIXIE, Tokai
Medical Products, Kasugai, Japan) through a 4F catheter. We
attempted superselective catheterization into tumor-feeding
branches in all cases; however, the catheter position was
controlled according to the tumor distributions and ana-
tomical variations. After injecting 0.5 mL of 2 % lidocaine
(Terumo, Tokyo, Japan), a mixture of 1–6 mL of iodized oil,
10–30 mg of epirubicin (Farmorbicin; Pfizer, Tokyo, Japan),
and 2–6 mg of mitomycin C (Mitomycin; Kyowa Hakko,
Tokyo, Japan) was slowly injected through the microcathe-
ter, followed by gelatin sponge particles (Gelfoam; Upjohn,
Kalamazoo, MI, or Gelpart; Nippon Kayaku, Tokyo, Japan)
that were crushed into approximately 0.2–0.5-mm particles
by pumping using a three-way stopcock valve and two 2.5-
mL syringes [16]. The total amount of iodized oil was
determined based on the tumor size (almost equal to the
diameter of the tumor). TACE was finished when the tumor-
feeding branch was completely obstructed and the tumor
stain disappeared on DSA.
CBCT Technique
An angiographic unit with a 38 930 cm
2
FPD (Allura
Xper FD20, Philips Healthcare) was used to obtain CBCT
images. In total, 312 projection images with X-ray
parameters of 120 kV and 200–300 mAs were obtained
with 207°rotation of the FPD around the patient for a 10.4-
s acquisition. Oxygen was administered to patients during
the procedure to minimize the discomfort of breath hold-
ing. Selective CBCTHA was performed 7 s after manual
injection of 2.5–5 mL of a half-diluted contrast material
(iopamiron 370 mg I/mL, Iopamiron 370, Bayer, Osaka,
Japan). LipCBCT was obtained after injection of a mixture
of 1–3 mL of iodized oil and anticancer agents through the
feeding branch. All CBCT images of 3-mm thickness were
observed using a workstation (Philips Healthcare).
Follow-up
Laboratory data, including serum total bilirubin (normal
range 0.2–1.0 mg/dL), aspartate aminotransferase (AST;
S. Miyayama et al.: Comparison of Local Effects in TACE With/Without CBCT Monitoring
123
normal range 10–40 U/L), alanine aminotransferase (ALT;
normal range 5–45 U/L), and prothrombin activity (PT;
normal range 70–130 %), were examined 1 day before
TACE, 1 day after TACE, 1 week after TACE, and every
1–3 months after TACE.
Unenhanced CT was obtained 1 week after TACE in all
patients to check for iodized oil distribution in the liver. All
patients were followed-up and dynamic CT and/or MRI
were performed every 2–3 months after the TACE proce-
dures to investigate any tumor recurrence. Local recurrence
was judged when an early-enhancing tumor without
iodized oil accumulation was observed in or adjacent to the
embolized tumor. Additional DSA and TACE were per-
formed for recurrent tumors, if possible.
Assessment
The v
2
test or unpaired ttests was used to evaluate sig-
nificant differences in the patient backgrounds in the DSA
and CBCT groups. The liver toxicity was evaluated using
the differences in the serum total bilirubin, AST, ALT, and
PT levels at 1 day after TACE compared with baseline in
the both groups and compared by the unpaired ttests.
We defined the embolized area as where iodized oil was
retained on 1 week after CT. The minimum safety margin
for the treatment was defined as a 5-mm wide for HCC
\25 mm and 10-mm wide for HCC C25 mm according to
a report by Sasaki et al. [17]. The technical success was
defined as achievement of a sufficient safety margin on
1 week after CT. According to these CT images, we clas-
sified technical success of TACE into three grades: (1)
grade A was defined as the embolized area included the
entire tumor with a circumferential safety margin; (2) grade
B was defined as the embolized area included the entire
tumor but the safety margin was not uniformly obtained
along all parts of the circumference; (3) grade C was
defined as the embolized area did not include the entire
tumor. The v
2
test was used to evaluate significant differ-
ences in the technical success of TACE in the DSA and
CBCT groups.
The local recurrence rates of tumors with grade A and
grade B were compared by the v
2
test. Cumulative local
recurrence rates in the DSA and CBCT groups were also
calculated by the Kaplan–Meier method and compared by
the log-rank test. Values of p\0.05 were considered
significant. Statistical calculations were performed using
software (StatView version 5.0; SAS, Cary, NC). The
conditions of local recurrent tumors were also analyzed
using serial CT, MRI, and DSA images.
Results
Results are summarized in Tables 1,2,3.
Patient Background
There were no significant differences in baseline patient
characteristics between the DSA and CBCT groups. The
tumor diameter of DSA group ranged from 7 to 54 mm
(mean, 22.2 ±10.1 mm) and that of the CBCT group
ranged from 8 to 60 mm (mean, 19.9 ±9.1 mm;
p=0.0855; Table 1).
Table 2 Grades of technical success of TACE in each group
Technical
success of
TACE
DSA
group
CBCT
group
Local
recurrence
(residual)
Grade A 64 (65.3 %) 95 (87.2 %) 46 (29.1 %)
Grade B 25 (25.5 %) 11 (10.1 %) 24 (66.7 %)
Grade C 9 (9.2 %) 3 (2.8 %) 12 (100 %)
Total 98 109 82 (39.6 %)
Table 1 Patient characteristics
of each group
HCV hepatitis C virus, HBV
hepatitis B virus, AST aspartate
aminotransferase, ALT alanine
aminotransferase
DSA group CBCT group pvalue
(n=70) (n=79)
No. of tumor 98 109
Sex (male/female) 39/31 47/32 0.6411
Age (year) 68.9 ±8.8 (40–86) 70.7 ±7.9 (46–89) 0.1505
Etiology (HCV/HB/others) 55/7/8 65/5/9 0.7102
Total bilirubin (mg/dL) 0.9 ±0.4 (0.4–2.5) 1.1 ±0.7 (0.3–3.4) 0.0914
AST (U/L) 53.8 ±30.5 (19–157) 51.9 ±29.2 (16–171) 0.4137
ALT (U/L) 46.7 ±27.9 (11–137) 45.3 ±32.7 (9–164) 0.7898
Prothrombin activity (%) 81.4 ±20.9 (41–130) 77.2 ±20.3 (34–130) 0.209
Child-Pugh class (A/B/C) 57/12/1 56/18/5 0.1879
Tumor size (mm) 22.2 ±10.1 (7–54) 19.9 ±9.1 (8–60) 0.0855
S. Miyayama et al.: Comparison of Local Effects in TACE With/Without CBCT Monitoring
123
Technical Success of TACE
Technical success in 159 tumors (76.8 %) was classified as
grade A, in 35 (16.9 %) as grade B, and in 13 (6.3 %) as
grade C (Figs. 1,2). Of 98 tumors in the DSA group,
technical success was classified as grade A in 64 (65.3 %),
grade B in 25 (25.5 %), and grade C in nine (9.2 %;
Fig. 1). In one tumor, TACE was performed through the
phrenic branch of the right internal mammary artery. Of
109 tumors in the CBCT group, technical success was
classified as grade A in 95 (87.2 %), grade B in 11
(10.1 %), and grade C in 3 (2.8 %; Fig. 2). In three tumors,
extrahepatic collateral vessels (two right inferior phrenic
arteries [IPA] and one left IPA) were sought and also
embolized according to CBCT findings. There was a sig-
nificant difference in the technical success of TACE
between the DSA and CBCT groups (p\0.001; Table 2).
The cause of grades B and C in the DSA group was
thought as missing some branches supplying the tumor and/
or safety margin. On the other hand, the causes of grade B
in the CBCT group were unsuccessful identification of a
feeding branch supplying the safety margin (n=5) or
insufficient evaluation of CBCT findings (n=8). In the
remaining four tumors, TACE was finished, although we
noticed that the safety margin was partially lacking because
the embolized area could become wider if additional TACE
Fig. 1 A 78-year-old man with HCCs treated with TACE using DSA
alone. ACT showed two tumors in the right lobe of the liver. BRight
hepatic arteriogram showed two tumor stains (arrows). CSelective
arteriogram of the anterior superior subsegmental artery of the right
hepatic artery showed a tumor stain. Arrow indicates the TACE point.
DSelective arteriogram of the paracaval branch of the caudate artery
of the liver also showed a tumor stain. TACE was performed at this
point. After TACE, the two tumor stains disappeared on DSA (not
shown). ECT obtained 1 week after TACE showed a defect of
iodized oil accumulation in one tumor (arrow). In another tumor, the
safety margin was not obtained at one dorsal part (arrowhead). FCT
obtained 3 months after TACE showed the tumor recurred at a site
without an adequate safety margin (arrow). Another tumor with
incomplete embolization was also enlarged (not shown)
Table 3 Procedural data and changes in laboratory data of each
group
DSA group CBCT group pvalue
(n=70) (n=79)
Dose of iodized oil (mL) 3.0 ±1.3 3.0 ±1.4 0.9456
Dose of epirubicin (mg) 16.7 ±6.9 15.5 ±7.2 0.325
Dose of mitomycin
C (mg)
3.4 ±1.4 3.1 ±1.4 0.1748
Total bilirubin (mg/dL)
a
0.2 ±0.4 0.1 ±0.3 0.4394
AST (U/L)
a
72.6 ±130.5 107.3 ±145.2 0.1219
ALT (U/L)
a
52.4 ±99.7 76.8 ±128.3 0.1936
Prothrombin
activity (%)
a
-(4.3 ±9.6) -(6.5 ±8.2) 0.1213
AST aspartate aminotransferase; ALT alanine aminotransferase
a
Difference of the serum level at 1 day after TACE compared with
baseline
S. Miyayama et al.: Comparison of Local Effects in TACE With/Without CBCT Monitoring
123
was performed. In one of three grade C tumors in the
CBCT group, a small tumor-feeding branch could not be
selected. TACE was finished because its parent artery
supplied a large area. In the remaining two tumors, TACE
was finished because we incorrectly thought that TACE
was completely performed due to overestimation of the
embolized area on LipCBCT by artifacts from densely
retained iodized oil.
Adverse Events of TACE
The most frequent adverse events observed in the present
study were fever, pain, and hepatic toxicity. There were no
statistically significant differences in changes in the serum
total bilirubin, AST, ALT, and PT levels 1 day after TACE
between the DSA and CBCT groups (total bilirubin,
0.2 ±0.4 mg/dL vs. 0.1 ±0.3 mg/dL [p=0.4394]; AST,
72.6 ±130.5 U/L vs. 107.3 ±145.2 U/L [p=0.1219];
ALT, 52.4 ±99.7 U/L vs. 76.8 ±128.3 U/L [p=0.1936];
and PT, -[4.3 ±9.6] % vs. -[6.5 ±8.2] % [p=0.1213],
respectively; Table 3). The laboratory data returned to the
baseline at 1 week after TACE in almost all patients. All
treatment-related adverse events were mild and within the
acceptable limits in both groups.
Local Tumor Control After TACE
The mean follow-up period with dynamic CT or MRI in the
DSA and CBCT groups was 44.1 ±25.9 (range, 8–105)
months and 34.3 ±15.5 (range, 4–61) months, respectively.
In total, 82 of 207 tumors (39.6 %) recurred after TACE.
In the DSA group, 48 tumors (49 %) recurred or had a
residual tumor portion 16.4 ±18.3 (range, 0–63) months
after TACE. In the CBCT group, 34 (31.2 %) recurred or
had a residual tumor portion 15.5 ±13.3 (range, 0–56)
months after TACE. The 1-, 2-, and 3-year local recurrence
rates in the DSA and CBCT groups were 33.3 and 22.3 %,
41.3 and 26.8 %, and 48 and 30.6 %, respectively (Fig. 3).
The cumulative local recurrence rates in the DSA group
were significantly higher than those of the CBCT group
(p=0.0217).
Regarding the technical success of TACE, 46 (29.1 %)
tumors with grade A recurred 16.7 ±16.6 (range, 3–65)
months after TACE and 24 (66.7 %) with grade B recurred
16.2 ±16.4 (range, 2–68) months after TACE. There was
a statistically significant difference in the local recurrence
rate after TACE between tumors with grades A and B
(p\0.001). All 12 grade C tumors also had a viable tumor
portion.
Fig. 2 A 73-year-old man with HCC treated by TACE under
monitoring of embolized areas using CBCT. ARight hepatic
arteriogram showed a tumor stain. BFirst, the branch of the posterior
superior subsegmental artery of the right hepatic artery (arrow in
Fig. 2A) was selected and a mixture of iodized oil and anticancer
agents was injected. CLipCBCT showed that the almost tumor was
included in the vascular territory but a small tumor portion at the left
side was not included (arrow). The safety margin was not also
obtained at the left side of the tumor. TACE was completed through
this vessel. DAnother branch of the anterior inferior subsegmental
artery of the right hepatic artery (arrowhead in Fig. 2A) was selected
and TACE was performed. ELipCBCT obtained immediately after
TACE showed that an adequate safety margin was obtained. FCT
obtained 1 week after TACE showed that the tumor was completely
embolized. GCT obtained 5 years and 3 months after TACE showed
that the tumor had decreased in size without recurrence
S. Miyayama et al.: Comparison of Local Effects in TACE With/Without CBCT Monitoring
123
Conditions of Local Recurrent Tumors
Of 46 recurrent tumors with grade A, iodized oil accumulated
in the tumor disappeared in19 tumors completely (n=11) or
partially (n=8). In 27 tumors, a viable tumor portion
developedadjacent to a tumor without an accumulated iodized
oil defect. Forty-three tumors were treated by additional
TACE and three were followed-up because of poor general
condition. On follow-up DSA, 30 were supplied by the ori-
ginal feeding branches, whereas 13 were supplied by the other
neighboring branches, including one middle colic artery.
Of 23 recurrent tumors with grade B, iodized oil accumu-
lated in the tumor completely disappeared in 4 tumors. In 19
tumors, a viable tumor developed adjacent to a tumor with or
without an accumulated iodized oil defect, at the site of an
inadequate safety margin (n=13; Fig. 1), at the site of a
complete safety margin (n=5), or surrounding the iodized oil
accumulated tumor (n=1). Twenty-one tumors were treated
by additional TACE and two were followed-up because of
poor general condition. On follow-up DSA, five tumors were
supplied by the original feeding branches, whereas 16 were
supplied by other feeding branches, including one left IPA.
All 12 grade C tumors were treated by additional TACE.
Four tumors were supplied by a small feeder arising from
the original feeding branch proximal to the previous TACE
point and eight were supplied by the other neighboring
hepatic arterial branches.
Discussion
Although TACE has widely been performed using DSA
alone, this method can fail to embolize the target tumors
completely. Combined CT-angiography system provides
sufficient information to perform complete TACE [4,5];
however, it is relatively expensive and requires a larger
room. CBCT is an alternative technology to obtain CT
images using an FPD-equipped C-arm system [8–15]. In
the literature, CBCT could provide information on chang-
ing the TACE procedures in 19–39 % of patients with HCC
that was planned with DSA alone [10,11]. Iwazawa et al.
[15] also reported that patients receiving CBCT-assisted
TACE had significantly higher overall and local progres-
sion-free survival rates than those receiving TACE with
DSA alone.
Local tumor control may be directly connected with the
prognosis of patients with inoperable HCC [7]. Histopa-
thologically, even small HCC lesions frequently have
capsular invasion and microsatellite lesions [17,18]. Sa-
saki et al. [17] reported that microsatellite lesions were
detected in 46 % of tumors B5 cm. These were observed in
7 (29.2 %) of 24 tumors \25 mm, and all but one of the
microsatellite lesions were located within 5 mm from the
main tumor. Therefore, we supposed that the safety margin
for the embolized area around a tumor \25 mm was at
least 5-mm wide. The safety margin around a tumor
C25 mm was at least 10-mm wide, and tumors located
outside of a 10-mm wide margin should be managed as
multicentrically developed tumors. The safety margin is
the most important factor for local control of HCC by
radiofrequency ablation (RFA) [19,20]. We consider that
embolization of the safety margin is also important for
local tumor control by TACE.
There are various causes of local tumor recurrence after
TACE. Missing a small tumor-feeder and insufficient
blockage of the feeding artery are the main technical fac-
tors and the presence of TACE-resistant tumor tissues is a
tumor-side factor [6,21–23]. In the present study, there
was a statistically significant difference in the technical
success rates of TACE between the DSA and CBCT
groups, and follow-up DSA showed a missing small feeder
in 10.1 % of tumors in the DSA group and 2.8 % of tumors
in the CBCT group. Recognition of a small feeder mainly
supplying the safety margin using DSA is difficult because
obvious tumor staining is not usually demonstrated even on
selective DSA. CBCT can depict whether the selected
branch is supplying the safety margin, although radiation
exposure and procedural time may increase. In the present
study, the local recurrence rates of tumors embolized with
an adequate safety margin were significantly lower than
those of tumors embolized without a circumferential safety
margin. Furthermore, tumors recurred more frequently at
sites where a safety margin was not obtained. This suggests
that security of the safety margin is an important factor to
reduce the local tumor recurrence after TACE. Security of
a circumferential safety margin is ideal; however, it is
Fig. 3 Local recurrence rates of the DSA and CBCT groups
calculated by the Kaplan–Meier method. The 1-, 2-, and 3-year local
recurrence rates in the DSA and CBCT groups were 33.3 and 22.3 %,
41.3 and 26.8 %, and 48 and 30.6 %, respectively. The cumulative
local recurrence rates in the DSA group were significantly higher than
those in the CBCT group (p=0.0217)
S. Miyayama et al.: Comparison of Local Effects in TACE With/Without CBCT Monitoring
123
sometimes invasive for patients with poor liver function
when the vascular territory of the residual feeder is large.
Performing additional TACE should be determined
according to a good balance of the vascular territory of the
feeding branch and the hepatic function reserve of each
patient. In the present study, TACE was reluctantly ended
without an adequate circumferential safety margin in six
tumors (5 with grade B and 1 with grade C) despite CBCT
monitoring, because it was estimated that a large area was
embolized by additional TACE. Control of the size of the
embolized areas by intraprocedural CBCT monitoring is
also important to avoid hepatic failure.
In 14 of 109 (12.8 %) tumors (11 with grade B and 3
with grade C), TACE was incomplete despite intraproce-
dural monitoring of the embolized area using CBCT,
although the incidence was low compared to that (22.5 %)
in a report by Iwazawa et al. [24]. Among these, eight
tumors with grade B and two with grade C were related to
inappropriate CBCT evaluation. CBCT images are low
contrast and motion artifacts mainly caused by inadequate
breath holding also reduce the image quality [14]. The
image artifacts can be reduced when a short-time acquisi-
tion protocol is used [13], and since 2010 we use a 5.2-s
scan protocol and 384 9384 matrix reconstruction in the
TACE procedure. In addition, some iodized oil injected
from the artery flows into the portal veins through the ar-
terioportal communications and tumor drainage [6,25,26].
It is frequently impossible to distinguish whether iodized
oil is distributed through the artery or the portal vein on
LipCBCT images obtained after when TACE is completed.
This may overestimate the embolized area during TACE.
Therefore, selective CBCTHA can demarcate the vascular
territory more precisely compared with LipCBCT. Lip-
CBCT should be obtained before the portal veins are
visualized with iodized oil, especially at the first embolized
branch of a tumor that is suspected of having multiple
feeders. We performed LipCBCT when 1–3 mL of a
mixture of iodized oil and anticancer agents was injected to
avoid overestimation of the embolized area.
Excessive advancement of a microcatheter has a risk of
missing a small feeder [6], and it occurred in 4.8 % of
tumors treated by DSA alone. In such tumors, an adequate
safety margin might be obtained when TACE was per-
formed at a more proximal level. However, we believe that
some tumor tissues supplied by both the arterial and portal
blood, such as a well-differentiated tumor portion, capsular
invasion, and microsatellite lesions, can be controlled only
when the both arterial and portal blood flow is blocked
[23]. It is essential to inject a mixture of iodized oil and
anticancer agents until overflow into the portal veins in
order to achieve complete tumor necrosis [26]; however,
such an embolization technique to a large area is invasive
and reduces hepatic function. For localized tumors,
therefore, we believe that TACE should be performed as
selectively as possible, although there is a risk of incom-
plete embolization [6].
Local tumor recurrence developed even in 29.1 % of
grade A tumors in the present study. In addition, in 14.3 %
of grade B tumors, the tumor recurred at a site where an
adequate safety margin was obtained. This is a limitation of
TACE and suggests that it may not consistently achieve
complete tumor necrosis even when it is successfully per-
formed [3,6]. As mentioned above, the causes of tumor
recurrence are wide-ranging and the security of the safety
margin is just one of these. This may explain why local
tumor recurrence develops more frequently after TACE
compared to RFA [3,4,6,18]. It is important to establish a
more effective TACE procedure, including the selection of
chemotherapeutic agents and embolic materials.
There are several limitations to the present study. First, we
did not consider the catheter position and magnitude of
TACE, which may strongly influence the therapeutic effects
as well as security of the safety margin [7]. Second, the
presence of TACE-resistant hypervascular HCC is well
known [27], and it may also influence the local tumor
recurrence rates. However, we cannot exclude such tumors
before TACE. Third, we did not evaluate the overall survival
rates because our cohort included several patients who had a
history of HCC treatment other than TACE. In addition, even
several patients in the CBCT group had other tumors that
were previously or simultaneously embolized without
monitoring of the embolized area using CBCT. From the
results of the present study, it could not be determined
whether the overall survival in the CBCT group was superior
to that of the DSA group. However, we believe that local
tumor control is one of the most important factors to improve
patient prognosis [7]. Finally, the CBCT protocol in the
present study was not the latest version. Further study is
needed to confirm the efficacy of CBCT in the superselective
TACE procedure using an up-to-date CBCT protocol. In
addition, now we use prototype TACE guidance software
using CBCT technology including auto-feeder detection
[28]. We believe that local effects of TACE may be improved
when such CBCT technology is routinely used.
In conclusion, intraprocedural monitoring of the em-
bolized area using CBCT improves the technical success of
TACE and reduces the local tumor recurrence rates com-
pared with TACE using DSA alone.
Conflict of interest None.
References
1. Yamada R, Sato M, Kawabata M et al (1983) Hepatic artery
embolization in 120 patients with unresectable hepatoma. Radi-
ology 148:397–401
S. Miyayama et al.: Comparison of Local Effects in TACE With/Without CBCT Monitoring
123
2. Uchida H, Ohishi H, Matsuo N et al (1990) Transcatheter hepatic
segmental arterial embolization using lipiodol mixed with an
anticancer drug and Gelfoam particles for hepatocellular carci-
noma. Cardiovasc Intervent Radiol 13:140–145
3. Matsui O, Kadoya M, Yoshikawa J et al (1993) Small hepato-
cellular carcinoma: treatment with subsegmental transcatheter
arterial embolization. Radiology 188:79–83
4. Takayasu K, Muramatsu Y, Maeda T et al (2001) Targeted
transarterial oily chemoembolization for small foci of hepato-
cellular carcinoma using a unified helical CT and angiography
system: analysis of factors affecting local recurrence and survival
rates. AJR Am J Roentogenol 176:681–688
5. Ishijima H, Koyama Y, Aoki J et al (1999) Use of a combined
CT-angiography system for demonstration of correlative anatomy
during embolotherapy for hepatocellular carcinoma. J Vasc Interv
Radiol 10:811–815
6. Miyayama S, Matsui O, Yamashiro M et al (2007) Ultraselective
transcatheter arterial chemoembolization with a 2-F tip micro-
catheter for small hepatocellular carcinomas: relationship
between local tumor recurrence and visualization of the portal
vein with iodized oil. J Vasc Interv Radiol 18:365–376
7. Morimoto M, Numata K, Sugimori K et al (2007) Successful
initial ablation therapy contributes to survival in patients with
hepatocellular carcinoma. World J Gastroenterol 13:1003–1009
8. Miyayama S, Yamashiro M, Okuda M et al (2009) Usefulness of
cone-beam computed tomography during ultraselective trans-
catheter arterial chemoembolization for small hepatocellular
carcinomas that cannot be demonstrated on angiography. Car-
diovasc Intervent Radiol 32:255–264
9. Hirota S, Nakao N, Yamamoto S et al (2006) Cone-beam CT with
flat-panel-detector digital angiography system: early experience
in abdominal interventional procedures. Cardiovasc Intervent
Radiol 29:1034–1038
10. Virmani S, Ryu RK, Sato KT et al (2007) Effect of C-arm
angiographic CT on transcatheter arterial chemoembolization of
liver tumors. J Vasc Interv Radiol 18:1305–1309
11. Wallace MJ, Murthy R, Kamat PP et al (2007) Impact of C-arm
CT on hepatic arterial interventions for hepatic malignancies.
J Vasc Interv Radiol 18:1500–1507
12. Kakeda S, Korogi Y, Ohnari N et al (2007) Usefulness of cone-
beam volume CT with flat panel detectors in conjunction with
catheter angiography for transcatheter arterial embolization.
J Vasc Interv Radiol 18:1508–1516
13. Miyayama S, Matsui O, Yamashiro M et al (2009) Detection of
hepatocellular carcinoma by CT during arterial portography using
a cone-beam CT technology: comparison with conventional
CTAP. Abdom Imaging 34:502–506
14. Miyayama S, Yamashiro M, Hattori Y et al (2011) Efficacy of
cone-beam computed tomography during transcatheter arterial
chemoembolization for hepatocellular carcinoma. Jpn J Radiol
29:371–377
15. Iwazawa J, Ohue S, Hashimoto N et al (2012) Survival after
C-arm CT-assisted chemoembolization of unresectable hepato-
cellular carcinoma. Eur J Radiol 81:3985–3992
16. Mori H, Saida Y, Wanatane Y et al (2000) Rapid production of
gelatin sponge particles for transcatheter arterial embolization:
pumping method. Nippon Acta Radiol 60:702–704 (in Japanese)
17. Sasaki A, Kai S, Iwashita Y et al (2005) Microsatellite distribu-
tion and indication for locoregional therapy in small hepatocel-
lular carcinoma. Cancer 103:299–306
18. Higashihara H, Okazaki M (2002) Transcatheter arterial chemo-
embolization of hepatocellular carcinoma: a Japanese experience.
Hepatogastroenterology 49:72–78
19. Nakazawa T, Kokubu S, Shibuya A et al (2007) Radiofrequency
ablation of hepatocellular carcinoma: correlation between local
tumor progression after ablation and ablative margin. AJR Am J
Roentgenol 188:480–488
20. Kim YS, Lee WJ, Rhim H et al (2010) The minimal ablative
margin of radiofrequency ablation of hepatocellular carcinoma
([2 and \5 cm) needed to prevent local tumor progression: 3D
quantitative assessment using CT image fusion. AJR Am J
Roentogenol 195:758–765
21. Ueda K, Saito K, Terada T et al (1991) Selective necrosis of
encapsulated malignant lesion within atypical adenomatous
hyperplasia of the liver following transarterial embolization. a
report of two autopsy cases. J Clin Gastroenterol 13:709–714
22. Takayasu K, Wakao F, Moriyama N et al (1993) Response of
early-stage hepatocellular carcinoma and borderline lesions to
therapeutic arterial embolization. AJR Am J Roentogenol
160:301–306
23. Miyayama S, Matsui O, Yamashiro M et al (2007) Iodized oil
accumulation in the hypovascular tumor portion of early-stage
hepatocellular carcinoma after ultraselective transcatheter arterial
chemoembolization. Hepatol Int 1:451–459
24. Iwazawa J, Ohue S, Kitayama T et al (2011) C-arm CT for
assessing initial failure of iodized oil accumulation in chemo-
embolization of hepatocellular carcinoma. AJR Am J Roentgenol
197:W337–W342
25. Terayama N, Matsui O, Gabata T et al (2001) Accumulation of
iodized oil within the nonneoplastic liver adjacent to hepatocellular
carcinoma via the drainage routes of the tumor after transcatheter
arterial embolization. Cardiovasc Intervent Radiol 24:383–387
26. Miyayama S, Mitsui T, Zen Y et al (2009) Histopathological
findings after ultraselective transcatheter arterial chemoemboli-
zation for hepatocellular carcinoma. Hepatol Res 39:374–381
27. Yamanaka K, Hatano E, Kitamura K et al (2012) Early evaluation
of transcatheter arterial chemoembolization-refractory hepato-
cellular carcinoma. J Gastroenterol 47:343–346
28. Miyayama S, Yamashiro M, Hashimoto M et al (2013)Identification
of small hepatocellular carcinoma and tumor-feeding branches with
cone-beam CT guidance technology during transcatheter arterial
chemoembolization. J Vasc Interv Radiol 24:501–508
S. Miyayama et al.: Comparison of Local Effects in TACE With/Without CBCT Monitoring
123
