Objectives: The aim of this study was to evaluate the success rate
in ultrasonography-guided ethanol ablation (EA) of benign, predominantly solid
thyroid nodules and to assess the value of colour Doppler ultrasonography in
prediction of its success.
Methods: From January 2008 to June 2009, 30 predominantly solid
thyroid nodules in 27 patients were enrolled. Differences in the success rate
of EA were assessed according to nodule vascularity, nodule size, ratio of
cystic component, amount of injected ethanol, degree of intranodular
echo-staining just after ethanol injection and the number of EA sessions.
Results: On follow-up ultrasonography after EA for treatment of
thyroid nodules, 16 nodules showed an excellent response (90% or greater
decrease in volume) and 2 nodules showed a good response (50–90% decrease in
volume) on follow-up ultrasonography. However, 5 nodules showed an incomplete
response (10–50% decrease in volume) and 7 nodules showed a poor response (10%
or less decrease in volume). Statistical analysis revealed a significant
association of nodule vascularity (p=0.002) and degree of intranodular echo-staining just
after ethanol injection (p=0.003) with a successful outcome; however, no such
association was observed with regard to nodule size, ratio of cystic component,
amount of infused ethanol and the number of EA sessions. No serious
complications were observed during or after EA.
Conclusion: The success rate of EA was 60%, and nodule vascularity
and intranodular echo-staining on colour Doppler ultrasonography were useful in
predicting the success rate of EA for benign, predominantly solid thyroid nodules.
Technique of ethanol ablation
Written informed
consent was obtained from all patients prior to each EA. EA was performed on an
out-patient basis by a radiologist according to the following method. The
operator used an empty 10-ml plastic syringe attached to either a conventional
21- or 23-gauge needle (23 gauge
for a purely solid nodule or a predominantly solid nodule with a smaller cystic
component, and 21 gauge for a predominantly solid nodule with a larger cystic
component). During the entire procedure, the operator manoeuvred the
ultrasonography probe with his left hand and the syringe–needle unit with his
right hand. The ultrasonography probe was adjusted for centring the target
nodule on the ultrasonography monitor.
The needle was
inserted rapidly almost perpendicular to the neck while the operator applied
positive pressure to the syringe piston using the thumb of his right hand in
order to prevent an influx of blood into the needle lumen. The method of ethanol
instillation differed according to whether the nodule was purely solid or
predominantly solid. In the case of a purely solid nodule, absolute ethanol
(99.9%) injection was administered directly.
Adequate coverage
of the target nodule, as indicated by its echogenicity (called intranodular
echo-staining), was achieved by adjusting the injection of ethanol under
ultrasonography guidance; the needle–syringe unit was then rapidly withdrawn
and the procedure was completed. In cases where the predominantly solid nodule
contained a cystic component, the cystic component was punctured and almost
completely aspirated, and an appropriate amount of ethanol was instilled. After
replacement of the needle into the solid component of the target nodule
by adjustment of the needle position, an appropriate amount of ethanol, which
was in proportion to nodule size and echo-staining of the solid portion of the
nodule, was infused. A single-puncture technique was used with no local
anaesthesia. In all cases the amount of injected ethanol did not exceed 10ml.
Any patient experiencing a sensation of drunkenness after EA was not allowed to
drive herself/himself home. Additional EA was performed 1–2 months after the
initial EA when the outcome of EA was determined to be unsuccessful on
follow-up ultrasonography. The amount of infused ethanol, degree of
intranodular echo-staining just after ethanol injection and presence of pain or
other complications during or after the procedure were recorded for each
patient.
Ultrasonography follow-up
Nodule
volume was calculated during the latest thyroid ultrasonography before EA and
during the final follow-up thyroid ultrasonography after EA. The difference in
nodule volume was used as a criterion for determination of the success or
failure of EA for treatment of thyroid nodules.
The other
factor was the absence of, or marked reduction in, nodule vascularity. The
outcome of EA was classified as follows, according to the decrease in nodule
volume and nodule vascularity: poor response ( <10% decrease in volume,
regardless of nodule vascularity), incomplete response (10–50% decrease in
volume, regardless of nodule vascularity), good response (50–90% decrease in
volume and decreased vascularity) and excellent response (> 90% decrease in
volume and scanty vascularity). On real-time colour Doppler ultrasonography,
nodule vascularity on the same-day ultrasonography, just before ethanol
injection, and that of the last follow-up ultrasonography after EA were
compared. Also, nodule volume measured on the same-day ultrasonography just
before ethanol injection and that of the last follow-up ultrasonography after
EA were compared. Furthermore, the success rate of EA was compared across the
nodule size, ratio of the cystic component, amount of infused ethanol, degree
of intranodular echo-staining by injected ethanol and the number of sessions of
EA. Intranodular echo-staining was roughly estimated on the basis of real-time
ultrasonography just after EA and classified as follows: no staining (nearly
complete washout of injected ethanol), poor staining ( <10% of the injected
area), mild staining (10–50% of the injected area) and moderate staining
( > 50% of the injected area) (Figure 1).
Discussion
Owing to its ease
of use, safety, low cost and effectiveness, EA is the first-choice tool for use
in the treatment of benign cystic thyroid nodules [17–26].
However, the
efficacy and results of EA for the treatment of solid or predominantly solid
thyroid nodules have been variable according to studies (Table 1) [2–14]. RFA
or laser ablation has recently become a safe modality for use as an appropriate
alternative to clinical follow-up, radioiodine therapy, surgery and EAtreatment
of benign solid thyroid nodules [27–30]. RFA has proven to be a feasible and effective
tool for treatment of solid nodules; however, its disadvantage lies in the high
cost when compared with EA. Baek et al [29] suggested that RFA for the
treatment of benign, predominantly solid thyroid nodules is effective for the
reduction of nodule volume and relief of nodule-related clinical problems; they
demonstrated a high success rate (100%) and a high mean volume reduction rate
(79.7%) during a 6-month period of ultrasonography follow-up. In the present
study, the mean success rate (60%) and volume reduction rate (64.3%) of EA were
lower than those reported by Baek et al [29].
In this study, a
significant relationship was observed between nodule vascularity and the
success rate of EA. EA of predominantly solid thyroid nodules with high vascularity
on colour Doppler ultrasonography showed worse results than those with low
vascularity. In addition, venous washout of injected ethanol was frequently observed
during EA of solid thyroid nodules with high vascularity. We found that poor
venous washout of injected ethanol during EA was closely related to good intranodular
echo-staining and good results, whereas moderate venous washout was closely
related to poor intranodular echo-staining and poor results. Consequently,
intranodular echo-staining is closely related to the success rate of EA. It may
be hypothesised that effective ethanol ablation is possible only when the ethanol
stays within the thyroid nodule and there is no venous washout of the injected
ethanol. A long stay of ethanol with little washout can have an effect on
sclerotic mechanisms of ethanol, which include coagulative necrosis,
small-vessel thrombosis and haemorrhagic infarction [31]. Therefore, EA may
become the first-line treatment when a symptomatic solid thyroid nodule shows
low- or isovascularity in colour Doppler ultrasonography.
Only one or two
EA sessions were conducted for each nodule in this study. We restricted
additional EA sessions in case of a significant appearance of venous washout of
the injected ethanol during the procedure or poor intranodular echo-staining
immediately after ethanol injection; therefore, no more than two EA sessions were
conducted. Furthermore, depending on nodule vascularity, degree of intranodular
echo-staining and an unsuccessful result on follow-up ultrasonography, an additional
EA session or RFA can be decided upon; thus, three or more EA sessions can be
avoided.
The fact that EA
of large solid thyroid nodules is less successful than EA of small ones is
generally accepted [5, 8, 9, 14, 24]; however, other studies have demonstrated safe
and effective techniques for treatment of large (.30ml) hyperfunctioning
nodules [12]. Some investigators have emphasised that a higher dose of ethanol
per session is more important than nodule size and could be significantly
related to EA success [12]. However, we believe that intranodular echo-staining
of the injected ethanol with no washout is more important than nodule size or
the amount of ethanol injected per session.
Kim et al [13]
insisted that the volume of instilled ethanol showed significant correlation
with the volume reduction rate of cysts, but not that of solid nodules. The percentage
of cystic components in the thyroid nodule has been shown to be closely
associated with successful EA [14]. However, in the present study, nodules with
a higher percentage of cystic components did not show good results in
comparison with nodules with a lower percentage of cystic components. If the
procedure were applied to predominantly solid thyroid nodules with low vascularity
and high echo-staining without venous washout, we could expect a higher success
rate before and during EA. Using this guideline for the selection of thyroid
nodules, we could improve the therapeutic results of benign predominant thyroid
nodules by choosing the most efficient therapeutic modality.
Ablation
mechanisms of ethanol include coagulative necrosis and small-vessel thrombosis
with haemorrhagic infarction [31]. An ablated portion of the nodule is replaced
by a granulation tissue, followed by progressive shrinkage. Except for
transient neck pain and discomfort, there was no occurrence of serious
complications of EA in our study. We think that the most serious complication
is necrosis of the adjacent normal soft and nerve tissue by leakage of injected
ethanol [11, 15, 32]. To avoid complications, substantial experience and a
precise ultrasound-guided injection are required. For reduction of side
effects, the amount of ethanol injected during each session did not exceed 10
ml in our study. There is no definite guideline for an adequate amount of
ethanol injected; in other studies, the maximum amount of ethanol injected per
session varied from 7 to 14ml without serious complication [9, 11, 12].
There were
several limitations to our study. First, the sample size was small and the
range of nodule sizes or configurations broad. Therefore, large-scale studies
are recommended in the future. Second, objective quantification of nodule
vascularity, intranodular echo-staining and venous washout of injected ethanol
was not performed. These were estimated and subsequently classified by the ultrasonography
operator. Finally, a thyroid scan was not performed before EA.
In summary, the
success rate of EA was 60%, and EA of predominantly solid nodules was more
effective in less vascular and more echo-staining thyroid nodules than in more
vascular and less echo-staining ones.
Therefore, colour
Doppler ultrasonography may be an useful tool for the prediction of treatment
outcomes for EA of benign, predominantly solid thyroid nodules.
