AJR 2003; 180:159-162
© American Roentgen Ray Society
Percutaneous Acetic Acid Injection for Hepatocellular Carcinoma: Using CT Fluoroscopy to Evaluate Distribution of Acetic Acid Mixed with an Iodinated Contrast Agent
Lionel Arrivé1,
Olivier Rosmorduc2,
Hervé Dahan1,
Laetitia Fartoux2,
Laurence Monnier-Cholley1,
Maïté Lewin1,
Raoul Poupon2 and
Jean-Michel Tubiana1
1 Service de Radiologie, Hôpital Saint-Antoine, 184 Rue du Faubourg Saint
Antoine, 75012 Paris Cedex, France.
2 Service d'Hépato-Gastro-Entérologie, Hôpital
Saint-Antoine, 75012 Paris Cedex, France.
Received December 7, 2001;
accepted after revision June 18, 2002.
Address correspondence to L. Arrivé.
Abstract
OBJECTIVE. The purpose of our study is to evaluate the distribution
of acetic acid mixed with iodinated contrast agent during percutaneous acetic
acid injection on CT fluoroscopy for hepatocellular carcinoma.
CONCLUSION. Monitoring acetic acid distribution on CT fluoroscopy
can detect extratumoral diffusion and may optimize the distribution of acetic
acid in hepatocellular carcinoma.
Introduction
Percutaneous ethanol injection is considered to be an effective alternative
to surgical resection for patients with cirrhosis and single hepatocellular
carcinoma [1]. Recent
experience reported from Japan with acetic acid injection into hepatocellular
carcinoma has shown encouraging results
[2]. More recently, Liang et
al. [3] suggested the safety
and efficacy of single-session percutaneous acetic acid injection.
However, time-dependent local intrahepatic recurrence of hepatocellular
carcinoma is frequent after percutaneous ethanol injection and percutaneous
acetic acid injection [1,
2]. Homogeneous distribution of
the contrast agent in the lesion is a prerequisite for effective therapy.
Therefore, the distribution of inhomogeneous contrast agent in the lesion may
be a limiting parameter for therapy response
[4]. Assessing the distribution
of contrast agent in the target area is one of the major difficulties of
percutaneous ethanol injection or percutaneous acetic acid injection. In
addition, uncontrolled spread of ethanol or acetic acid injection may be a
potential hazard of this treatment
[5].
When percutaneous ethanol injection or percutaneous acetic acid injection
is performed under sonographic guidance, a markedly hyperechoic or
heterogeneous focus usually appears immediately after the injection, which
sometimes may interfere with visualizing the exact extent of diffusion and
needle position. Therefore, an injection of a small volume of contrast agent
is usually performed per session, and repetition of sessions necessitates a
long treatment period [1]. CT
has been a guidance technique for percutaneous intervention for more than 20
years. As an interventional guidance tool, CT has been limited by a lack of
real-time capability in contrast to sonography. Recently, real-time CT
fluoroscopy has been used for different thoracic and abdominal applications,
including percutaneous ethanol injection
[6].
Our present prospective study was designed to evaluate the distribution of
acetic acid mixed with iodinated contrast agent during single-session
percutaneous acetic acid injection on CT fluoroscopy for hepatocellular
carcinoma.
Subjects and Methods
Patients
Forty-two patients who had cirrhosis and a total of 45 hepatocellular
carcinomas smaller than 5 cm in diameter underwent percutaneous acetic acid
injection with CT fluoroscopic guidance and monitoring. Thirty-two men and 10
women who ranged in age from 36 to 85 years old (mean age, 68 years) were
included in this study. Informed consent was obtained from each patient. The
cause of liver cirrhosis was alcohol intake in 19 patients, hepatitis C
infection in 14 patients, alcohol intake and hepatitis C infection in four
patients, and other causes in five patients.
The diagnosis of hepatocellular carcinoma was determined clinically in 29
patients (visualization of a de novo lesion on sonography by the same operator
and typical MR imaging appearance or 
-fetoprotein level > 500 ng/mL)
and histologically in 13 patients.
Procedure
The CT scanner used was a third-generation Somatom Plus 4 model with a
vision fluoroscopic CT option (Siemens Medical Systems, Erlangen, Germany).
Images were reconstructed and displayed at six frames per second. An in-room
mobile monitor with "last image hold" was used to view the
real-time images. The percutaneous acetic acid injection procedure was
performed while the patient was under general sedation and additional local
anesthetic. A 22-gauge Chiba end-hole needle 15-20 cm long (Becton Dickinson,
Franklin Lakes, NJ) was used for the puncture. A freehand technique was used
under CT fluoroscopic guidance. The needle was positioned in the center of the
lesion. The stylet was withdrawn, and the needle was connected via an
extension tube to a syringe filled with a mixture of 50% acetic acid and
nonionic contrast material (iohexol 300 [Omnipaque]; Nycomed Amersham,
Buckinghamshire, United Kingdom) at a ratio of 5:1. The theoretic volume of
50% acetic acid for the injection was calculated with
 |
where V is the volume of acetic acid and R is the radius of
the lesion in centimeters [2].
However, whatever the size of the lesion, a minimal volume of 3 mL of 50%
acetic acid was injected. Acetic acid was slowly injected under CT monitoring.
An intermittent, discontinuous CT fluoroscopic technique allowed monitoring of
acetic acid diffusion in the lesion.
If some areas of the lesion were not covered by the mixture of acetic acid
and contrast material, the needle was repositioned to optimize the
distribution. The objective was to obtain an even distribution of acetic acid
to cover the whole lesion. To detect acetic acid leaks, we performed
intermittent CT fluoroscopy at multiple levels combined with dynamic manual
table movement from the lower to the upper margin of the lesion. If CT
monitoring detected acetic acid escaping from the lesion, the injection was
stopped, and the needle position was adjusted.
The following data were prospectively recorded for the analysis of
diffusion of acetic acid: size, location of the lesions, and total injected
volume of acetic acid; mean distance of the skin or lesion and the number of
passes needed to ensure that the needle was positioned in the center of the
lesion; number of needle positions needed to optimize acetic acid
distribution; fluoroscopic time; procedure time, defined as the total time
between beginning local anesthesia and completion of percutaneous acetic acid
injection; examination time, defined as the total time between the first and
the last acquisition of the CT image; distribution of acetic acid through the
lesion complete, more than 75%, or less than 75%; and acetic acid leaks into
either peritumoral liver parenchyma, vessels, bile ducts, or the free
peritoneum.
Results
Fifty-seven sessions of percutaneous acetic acid injection were performed
in 42 patients and 45 hepatocellular carcinomas with an average size of 2.6 cm
(range, 1.2-5.0 cm). Lesions were located in the right lobe of the liver in 30
patients and in the left lobe of the liver in 15 patients. The average amount
of injected acetic acid was 8 mL (range, 3-30 mL). The mean distance of the
target lesion from the skin's surface was 5.9 cm (range, 2-10 cm). The average
number of needle passes from the skin to the lesion to ensure that the needle
was positioned in the center of the lesion in each procedure was 2.4 (range,
1-7). To improve acetic acid distribution, we required one to 10 (mean, 2.5)
needle repositionings in the lesion. In all patients, precise evaluation of
acetic acid distribution throughout the lesion was feasible by means of CT
fluoroscopic monitoring. The average CT fluoroscopic time was 2 min 5 sec
(range, 52 sec—4 min 20 sec), the average procedure time was 14 min
(range, 7-26 min), and the average examination time was 35 min (range, 18
min—1 hr 2 min).
An even distribution of acetic acid throughout the lesion to cover the
whole lesion was obtained in 30 sessions
(Fig. 1A). More than 75% of the
whole lesion was covered in 16 sessions
(Fig. 2). In the other 11
sessions, less than 75% of the whole lesion was covered, leaving more than 25%
of the lesion untreated (Fig.
3). We did not find any correlation between homogeneity of acetic
acid diffusion and tumor size. In all sessions, CT fluoroscopic monitoring
allowed effective repositioning to optimize the distribution of contrast agent
in the lesion (Fig. 4).
View larger version (174K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 1A. —85-year-old woman with hepatocellular carcinoma. CT
fluoroscopy image shows homogeneous distribution of acetic acid in lesion at
first positioning and injection. Despite peripheral location of lesion and
presence of perihepatic ascites, no extrahepatic leak was observed.
|
|
View larger version (145K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 2. —67-year-old woman with hepatocellular carcinoma. CT
fluoroscopy image obtained with three repositionings shows near homogeneous
distribution (>75%) of acetic acid in lesion. At first needle positioning,
tip of needle was pushed outside deeper border of lesion, and peritumoral leak
(arrow) was observed. Needle was pulled back, but leak persisted. No
further leak was observed after needle was repositioned.
|
|
View larger version (148K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 3. —60-year-old woman with hepatocellular carcinoma. CT
fluoroscopy image shows inhomogeneous distribution (<75%) of acetic acid in
lesion despite seven repositionings. Leak of acetic acid into peritoneum
(arrow) at periphery of lesion is shown.
|
|
View larger version (151K):
[in this window]
[in a new window]
[as a PowerPoint slide]
|
Fig. 4. —67-year-old woman with hepatocellular carcinoma. CT
fluoroscopy image shows heterogeneous distribution of acetic acid in semilunar
left part of lesion. Repositioning of needle tip centered in right untreated
part of lesion was performed to obtain homogeneous distribution.
|
|
Acetic acid leaks outside the lesion were encountered in 35 of 57 sessions.
Because different patterns of leaks were sometimes observed during the same
session, the total number of leaks was greater than 35. An analysis of
patterns of leaks was easily performed by CT fluoroscopic monitoring. Acetic
acid leaks in the peritumoral liver parenchyma were observed in 11 patients
(Figs. 1B and
2). Acetic acid leaks were
observed in distal bile ducts (n = 8), small portal veins (n
= 11), and small hepatic veins (n = 9)
(Fig. 5). Acetic acid leaks
were observed in the right portal vein in two patients and in the main bile
duct in three patients (Fig.
6). Extrahepatic leaks were observed in 10 patients in a
subcapsular location (n = 7) and in free peritoneum (n = 3)
(Fig. 3). However, as soon as a
leak was shown, injection was discontinued, and the needle was repositioned in
the lesion.
Discussion
We found that CT fluoroscopy was accurate for assessing the acetic acid
distribution in the lesion and detecting extratumoral leaks. Several factors
such as tumor consistency and heterogeneity, degree of vascularization, and
internal septa may limit the therapeutic effect of percutaneous acetic acid
injection [4]. By means of
pharmacokinetic imaging of 11C ethanol with positron emission
tomography, Dimitrakopoulou-Strauss et al.
[7] showed inhomogeneous drug
distribution in seven of eight patients undergoing percutaneous ethanol
injection. Therefore, precise monitoring of acetic acid distribution is
important, and homogeneous tumoral distribution is a prerequisite for
effective therapy. We did not find any correlation between homogeneity of
acetic acid diffusion and tumor size.
CT-guided ethanol injection has been suggested as one option in the
treatment of hepatocellular carcinoma to monitor diffusion of ethanol in the
tumor. Redvanly et al. [8] used
CT guidance to inject a large amount of ethanol. However, the injections were
performed without imaging monitoring, and several CT scans were obtained to
determine the position of the needle tip after puncture. Recently, real-time
CT fluoroscopy has been used for different thoracic and abdominal
applications, including percutaneous ethanol injection
[6]. Takayasu et al.
[9] suggested that using CT
fluoroscopy allowed single-session percutaneous ethanol injection for
treatment of hepatocellular carcinoma.
Usually, percutaneous ethanol injection and percutaneous acetic acid
injection are performed under sonographic guidance. Benefits claimed for
sonography include real-time monitoring, portability of the technology, and
low cost [1]. Sonography may
sometimes be limited for monitoring ethanol or acetic acid injection because a
markedly hyperechoic area appears immediately after injection. The hyperechoic
area may sometimes interfere with visualizing the exact extent of distribution
and needle position [4]. As a
result, a small volume of contrast agent injected per session necessitates
repetition of sessions and a relatively long treatment period. In addition,
sonography may be suboptimal to detect extratumoral leaks, especially in bile
ducts, portal vessels, and free peritoneum. Tapani et al.
[10] found, in studying the
accuracy of sonography in showing the spread of ethanol in pig livers, that
the distribution of ethanol to cover the lesion was overestimated and that
major leaks of ethanol outside the lesion were not detected.
The uncontrolled spread of ethanol or acetic acid may be a potential hazard
of this treatment. Peritumoral leaks may not necessarily be deleterious and
may even prevent local recurrences if leakage is uniform around the lesion. In
fact, peritumoral leakage is usually heterogeneous (Figs.
1A,1B
and 2). Leakage of acetic acid
into the systemic circulation via the hepatic veins has two potential
consequences: first, to decrease the concentration of acetic acid in the
tumor; and second, to expose the patient to the direct toxic effect of acetic
acid. Acute renal failure has already been reported as a complication of
acetic acid poisoning and as a complication of one case of percutaneous acetic
acid injection for hepatocellular carcinoma
[11]. Leakage of acetic acid
into the peritoneal space may result in localized peritonitis as reported by
Koda et al. [12]. In addition,
both hepatic infarction and liver perforation have already been reported
[3,
12]. To our knowledge, biliary
complications of percutaneous acetic acid injection have never been reported.
However, because the cytotoxic mechanisms of acetic acid are similar to those
of ethanol and result in coagulative necrosis of cells, cholangitis may occur
as a consequence of acetic acid leaks into bile ducts after percutaneous
acetic acid injection, as already reported after percutaneous ethanol
injection [5]. In our study,
detection of extratumoral leaks was facilitated by the combination of
intermittent CT fluoroscopy and manual table movement.
Our study was performed using a freehand technique, which may require
several punctures to achieve the desired location and may expose the
operator's hands to radiation. However, needle puncture—assisting
equipment has already been used and allowed accurate needle insertion and
minimal radiation exposure
[9].
Acknowledgments
We thank Pascale Dono for her assistance with preparation of this
article.
References
- Livraghi T, Giorgio A, Marin G, et al. Hepatocellular carcinoma and
cirrhosis in 746 patients: long-term results of percutaneous ethanol
injection. Radiology
1995;197:101
-108[Abstract/Free Full Text]
- Ohnishi K, Yoshioka H, Ito S, Fujiwara K. Prospective randomized
controlled trial comparing percutaneous acetic acid injection and percutaneous
ethanol injection for small hepatocellular carcinoma.
Hepatology
1998;27:67
-72[Medline]
- Liang HL, Yang CF, Pan HB, et al. Small hepatocellular carcinoma:
safety and efficacy of single high-dose percutaneous acetic acid injection for
treatment. Radiology
2000;214:769
-774[Abstract/Free Full Text]
- Bartolozzi C, Lencioni R. Ethanol injection for the treatment of
hepatic tumours. Eur Radiol
1996;6:682
-696[Medline]
- Koda M, Okamoto K, Miyoshi Y, Kawasaki H. Hepatic vascular and bile
duct injury after ethanol injection therapy for hepatocellular carcinoma.
Gastrointest Radiol
1992;17:167
-169[Medline]
- Daly B, Templeton PA. Real-time CT fluoroscopy: evolution of an
interventional tool. Radiology
1999;211:309
-315[Free Full Text]
- Dimitrakopoulou-Strauss A, Strauss LG, Gutzler F, et al.
Pharmacokinetic imaging of 11C ethanol with positron emission tomography in
eight patients with hepatocellular carcinomas who were scheduled for treatment
with percutaneous ethanol injection. Radiology
1999;211:681
-686[Abstract/Free Full Text]
- Redvanly RD, Chezmar JL, Strauss RM, Galloway JR, Boyer TD,
Bernardino ME. Malignant hepatic tumors: safety of high-dose percutaneous
ethanol ablation therapy. Radiology
1993;188:283
-285[Abstract/Free Full Text]
- Takayasu K, Muramatsu Y, Asai S, Muramatsu Y, Kobayashi T. CT
fluoroscopy-assisted needle puncture and ethanol injection for hepatocellular
carcinoma: a preliminary study. AJR
1999;173:1219
-1224[Abstract/Free Full Text]
- Tapani E, Vehmas T, Taavitsainen M. Ultrasound monitoring of
experimental ethanol injection into pig liver. Acad
Radiol 1994;1:21
-24[Medline]
- Van Hoof M, Joris JP, Horsmans Y, Geubel A. Acute renal failure
requiring haemodialysis after high doses percutaneous acetic acid injection
for hepatocellular carcinoma. Acta Gastroenterol Belg
1999;62:49
-51[Medline]
- Koda M, Tanaka H, Murawaki Y, et al. Liver perforation: a serious
complication of percutaneous acetic acid injection for hepatocellular
carcinoma. Hepatogastroenterology
2000;47:1110
-1112[Medline]
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
Top
Abstract
Introduction
