Long-Term Efficacy of Ethanol Ablation as Treatment of Metastatic Lymph Nodes From Papillary Thyroid Carcinoma
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The Journal of Clinical Endocrinology & Metabolism, 2022, XX, 1–7
https://doi.org/10.1210/clinem/dgab907
Advance access publication 18 December 2021
Clinical Research Article
Long-Term Efficacy of Ethanol Ablation as Treatment
of Metastatic Lymph Nodes From Papillary Thyroid
Carcinoma
Downloaded from https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgab907/6469671 by guest on 26 January 2022
Pål Stefan Frich,1,5, Eva Sigstad,2 Audun Elnæs Berstad,1, Kristin Holgersen Fagerlid,1,
Trond Harder Paulsen,3, Trine Bjøro,4,5, and Liv Ingrid Flinder1
1
Division of Radiology and Nuclear Medicine, Department of Radiology, Oslo University Hospital, 0424 Oslo, Norway
2
Division of Laboratory Medicine, Department of Pathology, Oslo University Hospital, 0424 Oslo, Norway
3
Division of Cancer Medicine, Department of Breast and Endocrine Surgery, Oslo University Hospital, 0424 Oslo, Norway
4
Division of Laboratory Medicine, Department of Medical Biochemistry, Oslo University Hospital, 0424 Oslo, Norway
5
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0318 Oslo, Norway
Correspondence: Pål Stefan Frich, MD, Department of Radiology, The Norwegian Radium Hospital, Oslo University Hospital, P.O. Box 4953, Nydalen N-0424
Oslo, Norway. E-mail: paafri@ous-hf.no.
Abstract
Context: Ethanol ablation (EA) is considered an alternative to surgery for metastatic lymph nodes from papillary thyroid carcinoma (PTC) in
selected patients.
Objective: The aim of this study was to evaluate the long-term efficacy and safety of this treatment.
Design and Setting: Adult patients with PTC who had received EA in lymph node metastasis at a tertiary referral center, and were included in
a published study from 2011, were invited to participate in this follow-up study.
Methods: Radiologic and medical history were reviewed. Ultrasound examination of the neck was performed by radiologists, and clinical exam-
ination was performed by an endocrine surgeon. Response was reported according to predefined criteria for satisfactory EA treatment. Adverse
events associated with EA were evaluated. Cause of death was reported for deceased patients.
Results: From the 2011 study, 51 of 63 patients were included. Forty-four patients were reexamined (67/109 lesions) and 7 patients were de-
ceased. Median follow-up time from primary surgery was 14.5 years. Median follow-up from the latest performed EA in the 2011 study was
11.3 years. Local control was permanently achieved in most patients (80%). Recurrence within an ablated node was registered in 13 metastases
in 10 patients. Seven of these patients also had recurrent disease elsewhere in the neck. No major side effects were reported.
Conclusion: EA is a minimally invasive procedure with a low risk of complications. Our data suggest that EA is a safe and efficient treatment,
providing excellent results for a large group of patients in the long term.
Abbreviations. EA, ethanol ablation; FNAB, fine-needle aspiration biopsy; PTC, papillary thyroid carcinoma; Tg, thyroglobulin;US, ultrasound
Treatment of small neck lymph node metastases from papil- primary surgery. The benefits of prophylactic lymph node dis-
lary thyroid carcinoma (PTC) is challenging. Our institution section are still controversial, but it is usually recommended
introduced, among the first institutions worldwide, ultra- in cases with advanced stage primary tumor (T3-4) (7, 8).
sound (US)-guided ethanol ablation (EA) as an optional treat- Studies have demonstrated a risk of recurrence in neck
ment for neck lymph node metastases from PTC in 2004 after lymph nodes ranging from 5% to 21%, with most of the
promising results from ethanol ablations were published in cases occurring within 10 years after primary treatment (9-
2002 by Lewis et al (1). Our results from treatment with EA 11). High-resolution US, thorough morphologic evaluation
in a 5-year period (2004-2009) were presented by Heilo et al and sensitive assays for detection of thyroglobulin (Tg) in
in 2011 (2). fine-needle aspiration biopsy washouts (FNAB-Tg) can detect
Neck lymph node metastases are common and found in metastases as small as 2 to 3 mm. The availability of such
20% to 50% of patients with PTC at diagnosis (3). With the tools contributes to an increase in the number of lymph node
use of more sensitive diagnostic methods, studies have re- metastases detected early in the clinical course, leading to a
ported a frequency of micrometastasis (< 2 mm) approaching clinical dilemma when the appropriate therapeutic approach
90% (4, 5). The presence of lymph node metastases is con- should be determined (12).
sidered an independent risk factor for increased morbidity Patients with persistent or recurrent disease in the thy-
and locoregional recurrent disease, but the effect on survival roid bed or neck lymph nodes after thyroidectomy and ad-
is still controversial (6). Surgical extirpation is recommended juvant radioiodine therapy may have limited benefit of a
when lymph node metastases are present before or during second radioactive therapy (13). The standard treatment for
Received: 10 September 2021. Editorial Decision: 13 December 2021. Corrected and Typeset: 10 January 2022
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://
creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the
original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@
oup.com2 The Journal of Clinical Endocrinology & Metabolism, 2022, Vol. XX, No. XX
recurrent disease is still considered to be surgery, although
it is well known that repeated neck surgery can be technic-
ally challenging because of adhesions, fibrosis, and scar tissue
with disruption of the normal anatomy and tissue planes (14,
15). Therefore, localized treatments like thermal ablation and
ethanol ablation have been proposed as alternatives to sur-
gery in selected patients with a limited number of metastases
or a high risk of local or general complications related to sur-
gery (3).
In 2011, our institution published the results from treat-
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ment of 109 neck lymph node metastases in 63 patients with
PTC (2). According to predefined criteria, a total of 92 (84%)
of the lymph nodes were successfully treated in the study.
The mean follow-up was 38 months (range, 3-72). No major
complications related to the EA treatment were recognized.
Additional studies with promising results from EA of nodal
neck metastasis have later been published, but the data for
long-term follow-up are still sparse (16-20). In this article, we
present the results from a long-term follow-up survey of the
patients from the 2011 study (2).
Materials and Methods
The study was approved by the Regional Committee for
Medical and Health Research Ethics. The cause of death was
obtained from the Norwegian Cause of Death Registry for
deceased patients.
Patients
Patients previously treated with EA in our initial report (2)
were identified and invited to participate in the follow-up
study. Of the 63 participating patients, 7 were deceased. One
patient had surgery following the first study and was lost to
follow-up. Forty-four of 55 eligible patients were successfully Figure 1. Flow chart of included patients.
included and reexamined in this study (Fig. 1). The remaining
11 patients did not give their active consent for participa- US-guided FNAB smear and FNAB Tg needle-wash spe-
tion or did not respond to the invitation. Of the reexamined cimen, as described by Sigstad et al, was undertaken when-
patients, 59% were female. Median age at follow-up was ever lymph nodes suspicious for metastases were detected
63 years (range, 35-86). Median interval since primary sur- (12). EA procedure was performed when considered clinically
gery was 14.5 years (range, 10-36). indicated, usually after a multidisciplinary team meeting, as
described by Heilo et al (2). Patients were informed about
possible adverse events before the procedure. The proced-
Methods ures were performed without premedication and coagulation
All the included patients had undergone total or subtotal tests. Total volume of injected ethanol and side effects were
thyroidectomy in 1 or 2 steps, followed by 131I-ablation. All recorded. The patients were discharged a short time after the
the patients had 3 or fewer metastatic lymph nodes at the procedure.
time of inclusion in the first study (2). The patients in the The patients were examined and interviewed by experienced
current study were reexamined on an outpatient basis. Last endocrine surgeons. Details from the medical history, experi-
known status concerning the patient’s PTC was obtained ences with prior treatment, and side effects from EA were
from the patient’s medical record and the radiological (RIS/ reviewed. The included and deceased patients were staged ac-
PACS) system. The patients were examined with US using cording to the American Joint Committee on Cancer Tumor
a 12.5 MHz broadband linear US transducer on GE Logiq Node Metastasis, 8th edition (Table 1) (21). Blood samples
E9 (GE Healthcare, Milwaukee, WI, USA). The US examin- were obtained for biochemical analysis (S-TSH, S-freeT4,
ations were performed by radiologists (K.H.F., L.I.F.) with S-Tg, and S-Tg antibodies). The outcomes of EA were con-
more than 5 years of experience of neck US examinations. We sidered successful when 1 or more of previously published
evaluated all previously confirmed neck lymph node metas- criteria were fulfilled (Table 2) (2). Recurrent disease was con-
tasis and registered any new lymph nodes being suspicious of firmed by morphological confirmation of FNAB smear and/
metastasis. The anteroposterior, transverse, and longitudinal or Tg-FNAB values greater than S-Tg values (not corrected
diameters were recorded, as was the efficacy of previous EA for dilution) in FNAB needle-wash sample. Recurrent disease
and time to recurrence. Any adverse events associated with in a location where EA had not been performed was defined
EA were evaluated. as recurrence outside of previously EA-treated lesions. LesionThe Journal of Clinical Endocrinology & Metabolism, 2022, Vol. XX, No. XX 3
volumes were calculated with the formula for the volume of Table 2. Criteria for satisfactory ethanol ablation
an ellipsoid (V=4 /3 · π · a · b · c ). Mann-Whitney U test was
used to compare median volumes of lesions with durable re- 1 Complete lymph node disappearance
sponse to recurrent lesions. Disease-specific death was calcu- 2 Reduction of the anteroposterior lymph node
lated for the deceased patients. diameter to ≤ 4 mm without visible vascularization
Tg (both in serum samples and in FNAB needle-wash sam- 3 Normalization of lymph node size and appearance,
ples) was measured with an in-house Tg assay and human and in some nodes scar formation
TgAb (in serum samples) was analyzed using a competitive 4 No detectable malignant cells in the FNAB specimens
assay (Brahms Kryptor, Henningsdorf, Germany) as de- and no detectable Tg in FNAB needle wash
scribed by Broughton et al (22). In the in-house Tg-assay
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4 monoclonal antibodies (E44 RRID:AB_2894939, E45 Abbreviations: FNAB, fine-needle aspiration biopsy; Tg, thyroglobulin.
RRID:AB_2894941, I24 RRID:AB_2894937, and E40
RRID:AB_2894934) were used. The 44 reexamined patients in the current study repre-
sented 67 of the 109 lesions (62%) in our initial report. The
number of EA-treated lesions in each of the reexamined pa-
Results tients ranged from 1 to 4, with most of the patients having 1
Out of the 63 eligible patients, 7 had died since the end of the (64%) or 2 (23%) lesions treated with ethanol ablations. The
study by Heilo et al (2). The deceased patients represented 15 remaining 27 lesions were distributed in the 12 nonincluded
of the 109 EA-treated lesions in our initial report, with a me- patients in this follow-up study (median 2; range, 1-6) with
dian of 1 EA-treated lesion per patient (range, 1-4). Six of the 75% of these patients having 1 or 2 lesions treated by EA in
7 deceased patients (86%) were females. The median age at the initial report. Most reexamined lesions (40/67) were in the
death was 68 years (range, 55-82). Median time from primary lateral compartments, whereas 27 lesions were located in the
surgery to death was 11 years (range, 5-35). The distributions central compartment. The median number of EA in each of
of disease stage (I-IV) in the reexamined and deceased patients the reexamined lesions in the initial study was 2 (range, 1-6)
differed significantly (median stage I vs II, U = 76, P = 0.042). with the majority (88%) having 1 to 3 EA procedure(s). The
There was no significant difference in the distribution of tumor median follow-up time since the latest performed EA in the
stage (T) or nodal status (N) in the 2 groups (Table 1). Thyroid initial study was 124 months (range, 90-160). Most of the pa-
cancer was identified as cause of death in 42.9% (3/7) of the tients (80%) were treated with EA in a single neck field, 18%
deceased patients, giving a cause-specific death in 4.8% (43/63) were treated in 2 fields, and 1 patient was treated in the cen-
of the patients from the 2011 study. Two of the patients with tral field as well as both lateral neck fields. Almost all lesions
cause-specific death had stage II disease and the last patient had reexamined in this study (97%) had fulfilled 1 or more of
stage III disease. All 3 patients were > 55 years at the time of the defined response criteria at the end of the study by Heilo
diagnosis (median 59; range, 58-76). et al. At follow-up, a durable response was demonstrated in
54 metastases (81%), of which a great majority (49) were
Table 1. Distribution of TNM statusa and disease stage at initial diagnosis
nondetectable, whereas 2 and 3 lesions fulfilled response cri-
teria 2 and 3, respectively (Table 2). Consequently, no FNAB
Included Deceased Test of significanceb
was performed in these lesions.
patients patients We registered a total of 13 recurrent lesions (in 10 pa-
tients) at the ablation site of earlier EA-treated lymph nodes,
No. % No. % giving a recurrence rate at the ablation site of 19%. Most of
Primary tumor these lesions were in the lateral neck (10), whereas the re-
maining 3 lesions were in the central compartment. Seven of
T1 9 20.5 2 28.6 P = 0.811
these residual lesions had been detected in the time before
T2 8 18.2 2 28.6 U = 122
the follow-up examination in the current study. Of these 7
T3 10 22.7 2 28.6 lesions, 1 had response from additional EA (Fig. 2A-C), 4 le-
T4 6 13.6 1 14.3 sions were still receiving EA, and 1 lesion was followed by
Tx 11 25.0 0 0.0 active surveillance at the time of inclusion. One lesion had
Nodal status been surgically removed, and this patient had no sign of re-
N0 6 13.6 1 28.6 P = 0.936 current disease at the time of the follow-up examination. The
N1 30 68.2 6 71.4 U = 123 remaining 6 lesions were detected at the follow-up exam-
ination in the current study. Three of these lesions, in 2 pa-
Nx 8 18.2 0 0.0
tients, were referred to surgery after consensus meetings in
Stage
our multidisciplinary team. Two recurrent lesions detected at
I 34 81.0 2 28.6 P = 0.042* follow-up, 1 in each of 2 patients, were considered unsuitable
II 4 9.5 4 57.1 U = 76 for surgery because of the candidates’ age and comorbidity,
III 4 9.5 1 14.3 and a new EA was consequently performed. The remaining
IV 0 0.0 0 0.0 lesion will be followed by active surveillance. The time frame
Missing 2 - for EAs, time of recurrence, and actual status of the recur-
rences in EA-treated lesions are shown in Fig. 3. In the 13
Abbreviation: TNM, tumor, node, metastasis. recurrent lesions, about one-half (6) had a diameter ≥ 10 mm
*Statistical significance level P < 0.05. (median 13.5 mm; range, 10-18). There was no significant
a
American Joint Committee on Cancer, 8th edition. All patients were
staged as M0 (no distant metastases) at initial diagnosis. difference in the initial volume of the lesions having durable
b
Mann-Whitney U test, 2-sided. response (median 125.7 mL; range, 6.3-1809.6), compared4 The Journal of Clinical Endocrinology & Metabolism, 2022, Vol. XX, No. XX
with recurring lesions (median 205.3 mL; range, 25.1-622.0)
(U = 406, P = 0.38). The median number of ethanol ablations
was similar (2) for lesions having durable response (range,
1-5) and recurring lesions (range, 1-6). The rate of recurrence
was 19.1% (9/47) in the lesions that had been nondetectable
(fulfilling diagnosis criteria 1 at the termination of the study
by Heilo et al, and 23.5% (4/17) in the lesions fulfilling any
other of the given response criteria.
We mapped a total of 22 neck lymph node metastasis (in 13
patients) in locations outside of previously EA-treated lesions.
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Sixteen of the lesions were in the lateral compartments and 6
in the central compartment. Most of these new lesions (14/22)
were found in 7 of the 10 patients who also experienced re-
current disease at the ablation site. Response after EA was
achieved in 42.9% (6/14) of the lesions in this patient group.
The remaining 8 lesions were found in 6 patients who also
had durable response in all their EA-treated lesions from the
initial report. All the new lesions in these patients responded
to EA after a median number of injections of 1.5 (1-4); thus,
none of the patients in this group had detectable disease at the
follow-up examination. All patients in the latter group, with
durable response in all lesions, had stage I disease. This was
the fact for only one-half of the patients in the group with
recurrences in ablated nodes and inferior efficacy of EA in
new lesions (median 1.5; range, 1-3, 1 missing value). The dif-
ference in distribution of disease stage between the 2 groups
was not significant (U = 9.0, P = 0.180), however. There was
no significant difference in the distribution of disease stage
between the group of reexamined patients experiencing re-
current disease in the follow-up time (n = 15, 1 missing value)
and those who did not have any recurrences (n = 27, 1 missing
value) (U = 226.50, P = 0.357).
There was no sign of recurrent disease in the neck in 80%
of the patients (35/44) at the time of follow-up. Even though
all patients had undergone radioiodine ablation following ini-
tial surgery, 6 patients in the group without detectable disease
(n = 35) had elevated S-Tg values and negative S-Tg antibodies
at follow-up. The measured S-Tg was low (≤ 1 µg/L) for 4 of
these patients. For the remaining 2 patients, the values were
3.7 and 4.3 µg/L, respectively. Two patients had nondetectable
S-Tg-values because of positive S-Tg antibodies.
In the group in which recurrent disease was detected
(n = 9), elevated S-Tg values (range, 0.60-37 µg/L) were seen
in 6 patients. Two patients had undetectable S-Tg values and
negative S-Tg antibodies and 1 patient had undetectable S-Tg
value and positive S-Tg antibodies.
Discussion
We present the long-term results from the so-far largest pub-
lished patient group treated with EA for metastatic neck
lymph nodes in patients with PTC (15). Local control was
Figure 2. A 72-year-old male patient had received EA in a total of 6
achieved in most patients (80%), with a median follow up of metastatic neck lymph nodes. Five had fulfilled the response criteria, but 1
11.3 years. However, recurrence within an ablated node was lesion in the right lateral compartment was still under active EA treatment
found in 13 EA-treated metastases in 10 patients. More than at follow-up. B-mode ultrasound images are showing a successfully
one-half of these patients (7/10) also had recurrent disease treated residual lesion in the central compartment. The lesion (white open
outside of previously ablated lesions. The observation time arrow) was initially treated with a single injection of 0.3 mL ethanol (A).
in our material is markedly longer (11.3 years) than prior The lesion was considered successfully treated with a remaining residual
lesion of 4 × 4 × 4 mm with no visible vascularity after 4 months (B).
studies evaluating this treatment. Recurrence with growth of the lesion (white solid arrow) and reappearance
Since Lewis et al presented their results from EA in recur- of vascularization occurred 7 years after the initial ablation (C). The lesion
rent neck lymph node disease in 2002 (1), several studies was then treated with a total of 4 additional ethanol injections and has
have been published, suggesting a favorable outcome of this been persistently undetectable on later follow-up examinations.The Journal of Clinical Endocrinology & Metabolism, 2022, Vol. XX, No. XX 5
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Figure 3. The figure displays the time course of 13 recurrences found at the ablation site in 10 patients. The top line displays the number of years (Y)
of follow-up. The horizontal lines to the left represent time periods where the initial ethanol injections were performed. The horizontal lines to the right
display the time of recurrence and actual status of the recurrent lesions. Closed lines represent completed series of ethanol ablations, whereas open
lines are indicating ongoing treatment with ethanol ablations.
treatment (2, 16-20, 23-26). Size reduction is seen in > 90% comparable recurrence rate in these lesions compared with
of the treated lesions and a significant number of lesions the lesions with complete disappearance after EA treatment.
are not detectable on US after successful EA treatment. The It has been proposed that EA is more effective in treating
first published studies, up until 2011, reported low rates of tiny metastatic lesions. Strajina et al found significant differ-
local progression or recurrences within ablated nodes (1, 2, ences between the initial size of the lesions and the differences
23-26). These findings could be due to the relatively shorter in treatment response from EA (17). The initial diameter of
follow-up times compared with later case series. In a study the recurring EA-treated lesions in our material ranged from
from 2013, local progression was seen in 23.8% (5/21) of 4 to 18 mm, with about one-half the lesions (6/13) having a
the lesions after a mean follow-up of 38.5 months (range, diameter ≥ 10 mm. The recurring lesions in our material did
0-94) (20). This contrasts with the results published by Hay not have a significantly larger initial volume than the success-
et al the same year, in which no local progression within an fully treated lesions; however, the numbers are small and en-
ablated node was reported after a mean follow-up-time of cumbered with uncertainty.
65 months (range, 5-157) (19). The latter study found, how- Because EA represents a selective treatment of confirmed
ever, increasing size of 2/37 lesions in 1 patient during the lymph node metastases, resembling a “berry-picking” pro-
follow-up time, but these lesions were still considered suc- cedure, the risk of subsequent recurrences in locations out-
cessfully treated because of the lack of vascularization and side of the ablation sites are of concern. We detected “new”
undetectable S-Tg-level at 110 months. Strajina et al reported neck lymph node metastases in 27% (12/44) of the patients
progression within an ablated node in 16% of the EA-treated in our material. One-half of these also had recurrent disease
lateral neck lymph nodes (7/43) after a median follow-up of in 1 or more of the EA ablation sites. The other one-half
54 months (range, 6-102) (17). A recurrence rate of 19% of had persistent response in their EA-treated lesions while ex-
the treated lesions was found in the current study. The rate is periencing new lesions elsewhere in the neck. Two studies
within the range of the previously reported suggesting that reported the proportion of patients with “new” lesions to be
a prolonged observation time would not necessarily lead to 9% and 24%, respectively (17, 19). In light of the longer
an increasing number of recurrences (17, 20). Unfortunately, follow-up time in this case series, our results suggest that the
several of the patients in our study were not summoned for proportion of patients with new lesions outside the ablation
regular follow-up. Consequently, the time from the last pre- sites would not increase with time after diagnosis. The results
ceding EA to occurrence of recurrence was not assessable. are, however, not conclusive. Most of the new lesions in our
The number of complete disappearances in our long-term material were found in patients who also had recurrences at
follow-up was slightly higher (73%), but comparable to the the ablation site of lesions treated in the initial report. These
numbers previously reported. There has been some concern patients had a poorer efficacy of EA in the new lesions than
about the risk of residual tumor deposits in the lesions that the patients without recurrent EA-treated lesions, with dur-
show a decrease in size, but still are visible on US. Lim et al able response in less than one-half of the lesions. This con-
performed FNAB on all detectable lesions after EA and found trasts with Hay et al reporting successful EA treatment of 15
that tumor cells were present in 75% (15/20) of the cases, but lesions outside of the ablation site (19), which is consistent
no further increase in the size of these lesions were seen during with our results from EA in the new lesions in the group
the follow-up period (25). We found a slightly higher, but without recurrences within ablated lesions. The reason for6 The Journal of Clinical Endocrinology & Metabolism, 2022, Vol. XX, No. XX
the difference in efficacy between the 2 groups is not clear. Funding
All patients in the group with durable response in all their le-
This work was supported from The Radium Hospital
sions had stage I disease, whereas one-half of the patients in
Foundation (grant #192011) and Ødegaard and Frimann-
the group with recurrences in ablated nodes and inferior effi-
Dahls foundation (grant #8225).
cacy of EA in new lesions had disease stage II-III. This could
imply that more aggressive disease in these patients could
be a contributing factor to this effect, but the difference in Disclosures
distribution of disease stage between the 2 groups was not
The authors have nothing to disclose.
significant, however.
Surgery is still considered to be the treatment of choice
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for lymph node metastases from PTC, but there are still no Data Availability
randomized trials comparing EA and surgery. In a system- Some or all datasets generated during and/or analyzed during
atic review and pooled analysis by Fontenot et al in 2015, the current study are not publicly available but are available
the success rate of surgery was slightly higher than the suc- from the corresponding author on reasonable request.
cess rate for EA treatment (94.8% vs 87.5%) (27). They
found no significant difference in risk of recurrence in the References
treated lesion or elsewhere in the neck. The comparison be-
1. Lewis BD, Hay ID, Charboneau JW, McIver B, Reading CC,
tween the methods was complicated by an uneven distribu-
Goellner JR. Percutaneous ethanol injection for treatment of cer-
tion with more lesions in the central compartment treated vical lymph node metastases in patients with papillary thyroid car-
with surgery than EA. Despite surgery being the treatment cinoma. AJR Am J Roentgenol. 2002;178(3):699-704.
of choice, the indolent nature of the disease is making the 2. Heilo A, Sigstad E, Fagerlid KH, et al. Efficacy of ultrasound-guided
goal of managing recurrent or persistent lymph node metas- percutaneous ethanol injection treatment in patients with a limited
tasis a persistent matter of controversy. From the patient’s number of metastatic cervical lymph nodes from papillary thyroid
perspective, it seems like a reasonable strategy to get rid of carcinoma. J Clin Endocrinol Metab. 2011;96(9):2750-2755.
any sign of disease and prevent recurrences. The choice of 3. Haugen BR, Alexander EK, Bible KC, et al. 2015 American
treatment must be balanced against the risk for adverse ef- Thyroid Association management guidelines for adult patients with
thyroid nodules and differentiated thyroid cancer: the American
fects and complications from the treatment that might im-
Thyroid Association guidelines task force on thyroid nodules and
pair the patients function and/or quality of life, however.
differentiated thyroid cancer. Thyroid: Off J Am Thyroid Assoc.
Since the study by Heilo et al, there has been a change in the 2016;26(1):1-133.
approach to locoregional recurrences of PTC. Studies have 4. Arturi F, Russo D, Giuffrida D, et al. Early diagnosis by genetic
confirmed that a considerable number of tiny metastatic analysis of differentiated thyroid cancer metastases in small lymph
neck lesions do not progress, or possibly progress slowly nodes. J Clin Endocrinol Metab. 1997;82(5):1638-1641.
and without affecting the patient’s function or comprom- 5. Qubain SW, Nakano S, Baba M, Takao S, Aikou T. Distribution
ising neighboring structures (28-30). Thus, it has become of lymph node micrometastasis in pN0 well-differentiated thyroid
more acceptable to follow small and nonprogressive lesions carcinoma. Surgery. 2002;131(3):249-256.
by active surveillance. 6. Mansour J, Sagiv D, Alon E, Talmi Y. Prognostic value of lymph
node ratio in metastatic papillary thyroid carcinoma. J Laryngol
Our results support the present consensus that EA should
Otol. 2018;132(1):8-13.
be considered an alternative to repeated neck surgery in
7. Gambardella C, Tartaglia E, Nunziata A, et al. Clinical significance
selected patients with increased risk associated with surgery of prophylactic central compartment neck dissection in the treat-
and general anesthesia, as well as for patients refusing to ment of clinically node-negative papillary thyroid cancer patients.
undergo additional surgery. The treatment is shown to make World J Surg Oncol. 2016;14(1):247.
most of the lesions fulfill the response criteria. Furthermore, 8. Grubbs EG, Evans DB. Role of lymph node dissection in pri-
locoregional control in the neck region is achievable in most mary surgery for thyroid cancer. J Natl Compr Canc Netw.
patients, also in the long term. We achieved local control after 2007;5(6):623-630.
a limited number of injections for a limited period for most 9. Grant CS. Recurrence of papillary thyroid cancer after optimized
of the patients. The efficacy of EA in recurrences in previously surgery. Gland Surg. 2015;4(1):52-62.
10. Liu FH, Kuo SF, Hsueh C, Chao TC, Lin JD. Postoperative recur-
ablated nodes, as well as in new recurrent lesions in the same
rence of papillary thyroid carcinoma with lymph node metastasis. J
patients, was inferior to the overall efficacy. Based on our ex-
Surg Oncol. 2015;112(2):149-154.
periences, a lower threshold for the consideration of other 11. Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and
treatment alternatives than EA should be obtained in these medical therapy on papillary and follicular thyroid cancer. Am J
cases. We did not detect any major or persisting side effects in Med. 1994;97(5):418-428.
this long-term follow-up. The result is in accordance with sev- 12. Sigstad E, Heilo A, Paus E, et al. The usefulness of detecting
eral previous reports, concluding that EA could be considered thyroglobulin in fine-needle aspirates from patients with neck
a safe and well-tolerated treatment option (1, 2, 16-20, 23-26). lesions using a sensitive thyroglobulin assay. Diagn Cytopathol.
In a recent overview article, the authors favor the use of 2007;35(12):761-767.
EA for locally recurrent differentiated thyroid carcinoma in 13. Hirsch D, Gorshtein A, Robenshtok E, et al. Second radioiodine
treatment: limited benefit for differentiated thyroid cancer
nonsurgical candidates (31). However, they emphasize the
with locoregional persistent disease. J Clin Endocrinol Metab.
need for randomized controlled trials to clarify the true value
2018;103(2):469-476.
and risks of the treatment. 14. Lombardi CP, Raffaelli M, De Cre, C, Sessa L, Bellantone R.
In conclusion, EA is a safe and efficient treatment, pro- Morbidity of central neck dissection: primary surgery vs
viding excellent results for a large group of patients also in reoperation. Results of a case-control study. Langenbecks Arch
the long run. Surg. 2014;399(6):747-753.The Journal of Clinical Endocrinology & Metabolism, 2022, Vol. XX, No. XX 7
15. Shen WT, Ogawa L, Ruan D, et al. Central neck lymph node dissec- 24. Monchik JM, Donatini G, Iannuccilli J, Dupuy DE. Radiofrequency
tion for papillary thyroid cancer: comparison of complication and ablation and percutaneous ethanol injection treatment for recur-
recurrence rates in 295 initial dissections and reoperations. Arch rent local and distant well-differentiated thyroid carcinoma. Ann
Surg. 2010;145(3):272-275. Surg. 2006;244(2):296-304.
16. Vannucchi G, Covelli D, Perrino M, De Le, S, Fugazzola L. Ultrasound- 25. Lim CY, Yun JS, Lee J, Nam KH, Chung WY, Park CS. Percutaneous
guided percutaneous ethanol injection in papillary thyroid cancer ethanol injection therapy for locally recurrent papillary thyroid
metastatic lymph-nodes. Endocrine. 2014;47(2):648-651. carcinoma. Thyroid. 2007;17(4):347-350.
17. Strajina V, Dy BM, McKenzie TJ, et al. Treatment of lateral neck 26. Kim BM, Kim MJ, Kim EK, Park SI, Park CS, Chung WY.
papillary thyroid carcinoma recurrence after selective lateral neck Controlling recurrent papillary thyroid carcinoma in the neck
dissection. Surgery. 2019;165(1):31-36. by ultrasonography-guided percutaneous ethanol injection. Eur
18. Kim SY, Kim SM, Chang H, et al. Long-term outcomes of ethanol Radiol. 2008;18(4):835-842.
Downloaded from https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgab907/6469671 by guest on 26 January 2022
injection therapy for locally recurrent papillary thyroid cancer. Eur 27. Fontenot TE, Deniwar A, Bhatia P, Al-Qurayshi Z, Randolph GW,
Arch Otorhinolaryngol. 2017;274(9):3497-3501. Kandil E. Percutaneous ethanol injection vs reoperation for lo-
19. Hay ID, Lee RA, Davidge-Pitts C, Reading CC, Charboneau JW. cally recurrent papillary thyroid cancer: a systematic review
Long-term outcome of ultrasound-guided percutaneous ethanol ab- and pooled analysis. JAMA Otolaryngol Head Neck Surg.
lation of selected “recurrent” neck nodal metastases in 25 patients 2015;141(6):512-518.
with TNM stages III or IVA papillary thyroid carcinoma previously 28. Urken ML, Milas M, Randolph GW, et al. Management of
treated by surgery and 131I therapy. Surgery. 2013;154(6):1448- recurrent and persistent metastatic lymph nodes in well-
1454; discussion 1454-1445. differentiated thyroid cancer: a multifactorial decision-making
20. Guenette JP, Monchik JM, Dupuy DE. Image-guided abla- guide for the thyroid cancer care collaborative. Head Neck.
tion of postsurgical locoregional recurrence of biopsy-proven 2015;37(4):605-614.
well-differentiated thyroid carcinoma. J Vasc Interv Radiol. 29. Rondeau G, Fish S, Hann LE, Fagin JA, Tuttle RM.
2013;24(5):672-679. Ultrasonographically detected small thyroid bed nodules identified
21. Tuttle RM, Haugen B, Perrier ND. Updated American Joint after total thyroidectomy for differentiated thyroid cancer seldom
Committee on Cancer/tumor-node-metastasis staging system for show clinically significant structural progression. Thyroid: Off J
differentiated and anaplastic thyroid cancer (eighth edition): what Am Thyroid Assoc. 2011;21(8):845-853.
changed and why? Thyroid. 2017;27(6):751-756. 30. Robenshtok E, Fish S, Bach A, Dominguez JM, Shaha A,
22. Broughton MN, Nome R, Sandven I, Paus E, Bjoro T. Tuttle RM. Suspicious cervical lymph nodes detected after thy-
Characterization of a new highly sensitive immunometric assay roidectomy for papillary thyroid cancer usually remain stable
for thyroglobulin with reduced interference from autoantibodies. over years in properly selected patients. J Clin Endocrinol Metab.
Tumour Biol. 2016;37(6):7729-7739. 2012;97(8):2706-2713.
23. Sohn YM, Hong SW, Kim EK, et al. Complete eradication of met- 31. Paz-Fumagalli R, Li X, Smallridge RC. Ethanol ablation of neck
astatic lymph node after percutaneous ethanol injection therapy: metastases from differentiated thyroid carcinoma. Semin Intervent
pathologic correlation. Thyroid. 2009;19(3):317-319. Radiol. 2019;36(5):381-385.You can also read
