Fendo 13 921812
Fendo 13 921812
Fendo 13 921812
REVIEWED BY
for multifocal papillary
Lin Yan,
PLA General Hospital, China
Zhijiang Han,
thyroid microcarcinoma
Hangzhou First People’s Hospital,
China
Lu Zhang, Gui Ping Zhang, Wei Wei Zhan and Wei Zhou *
*CORRESPONDENCE
Wei Zhou Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai JiaoTong University,
[email protected] Shanghai, China
SPECIALTY SECTION
This article was submitted to
Thyroid Endocrinology,
a section of the journal Objective: The aim of this study was to evaluate the feasibility and efficacy of
Frontiers in Endocrinology
percutaneous laser ablation (PLA) for patients with multifocal papillary thyroid
RECEIVED 16 April 2022 microcarcinoma (PTMC).
ACCEPTED 26 July 2022
PUBLISHED 17 August 2022
Materials and methods: A cohort of patients who underwent ultrasound (US)-
CITATION
Zhang L, Zhang GP, Zhan WW and
guided PLA for primary PTMC were enrolled in this study. The patients were divided
Zhou W (2022) The feasibility and into a multifocal PTMC (multi-PTMC) group and a unifocal PTMC (uni-PTMC)
efficacy of ultrasound-guided group. Before PLA, conventional US and contrast-enhanced ultrasound (CEUS)
percutaneous laser ablation for
multifocal papillary thyroid were performed to evaluate the PTMC and cervical lymph nodes. The operation
microcarcinoma. time, energy, power, amount of isolation liquid, and complications during PLA
Front. Endocrinol. 13:921812.
doi: 10.3389/fendo.2022.921812
were recorded. Patients were followed up at 2 days, 1 month, 3 months, and 6
months, and every 6 months after that. Volume reduction rate (VRR), local tumor
COPYRIGHT
© 2022 Zhang, Zhang, Zhan and Zhou. recurrence, and lymph node metastasis after PLA were observed.
This is an open-access article
distributed under the terms of the Results: The study included 12 patients with 26 PTMCs and 60 patients with 60 PTMCs.
Creative Commons Attribution License
(CC BY). The use, distribution or The operationtime,total energy, and amountofisolationliquidinthe multi-PTMC group
reproduction in other forums is were more than those in the uni-PTMC group (p = 0.000, 0.007, and 0.020,
permitted, provided the original
respectively). The mean follow-up durations in multi-PTMC and uni-PTMC groups
author(s) and the copyright owner(s)
are credited and that the original were 19.75 ± 11.46 months (6–36 months) and 16.33 ± 10.01 months (4–40 months),
publication in this journal is cited, in with a similar VRR of the ablated lesions in the two groups. One and three cases with
accordance with accepted academic
practice. No use, distribution or newly developed PTMCs were observed in the multi-PTMC group and the uni-PTMC
reproduction is permitted which does group during follow-up, respectively. There was no regrowth of treated lesions, lymph
not comply with these terms.
node metastasis, or distant metastasis. At the end of the follow-up, all the ablated lesions
in the two groups completely disappeared or only remained scar strips.
Conclusion: PLA is a safe and effective technique for treating multifocal PTMC,
which might be an alternative technique for patients who are not eligible or are
unwilling to undergo surgery.
KEYWORDS
Background performed for all the patients before the PLA procedure, and
written informed consent was obtained after informing patients
Thyroid cancer is the most common malignant tumor among of the possible risks and complications of treatment.
endocrine neoplasms, of which papillary thyroid microcarcinoma The inclusion criteria were as follows: (1) all the nodules
(PTMC) accounts for more than 84% (1). The traditional treatment were diagnosed as PTC by FNAB, with no sonographic evidence
strategy for PTMC is hemithyroidectomy or total thyroidectomy. of capsular infiltration and extrathyroidal extension; (2) the
However, the proportion of thyroid cancer in female cases maximum diameter of the nodule was no more than 10 mm;
attributable to overdiagnosis from 2008 to 2012 was about 87% in (3) in the multi-PTMC group, the number of PTMC in every
China (2). This indicates that there might be overtreatment of patient was not less than two, and nodules were located in
PTMC in clinical practice (3). The 2015 American Thyroid unilateral or bilateral lobes; and (4) patients were not eligible or
Association Management Guidelines for Adult Patients with were unwilling to undergo surgery. The exclusion criteria were
Thyroid Nodules and Differentiated Thyroid Cancer suggested as follows: (1) combination with other types of thyroid
that an active surveillance approach can be considered in some malignancies, such as medullary carcinoma, undifferentiated
patients with low-risk PTMC (4); however, it would evoke major carcinoma, and thyroid metastatic carcinoma; (2) the nodule
anxiety if the tumor is left untreated, and repeated and regular was located in the isthmus; and (3) detection of metastatic lymph
ultrasound (US) examinations will be performed. Therefore, non- nodes in the neck or distant metastasis.
surgical thermal ablation treatments might be alternative methods
for these cases.
Percutaneous laser ablation (PLA) is the first reported
thermal ablation technology applied to PTMC (5). It can Preoperative evaluation
treat tumors by converting laser energy into thermal energy,
which causes coagulation and necrosis. PLA is regarded as a Medical history was obtained before PLA, and relevant
minimally invasive treatment for solitary tumor due to its examinations were performed, including thyroid function, liver
advantages of precise ablation range, high safety, minimal and kidney function, blood routine and virus indicators analysis,
trauma, and quick postoperative recovery (6–10). However, chest x-ray/CT, and electronic laryngoscopy. US was performed
previous studies mainly focused on the results of unifocal using a real-time US instrument (Mylab Twice and Mylab 9,
PTMC, rather than multifocal PTMC. The incidence of Esaote, Italy) equipped with multi-frequency linear probes (LA
multifocality in papillary thyroid cancer (PTC) is 32%–39%, 523, L4-15 and LA 332, L3-11). The number, location,
and it is often regarded as a risk factor, but the role in the characteristics, volume of thyroid nodules, and bilateral
prognosis remains unclear (11). The results of many studies on cervical lymph nodes were carefully evaluated on imaging.
the role of multifocality in the clinical outcome of PTC were Three radial lines were measured, including anteroposterior
inconsistent and even contradictory (12–15). Several studies diameter, transverse diameter, and longitudinal diameter
had been carried out on RFA for multifocal PTMC, and the (V = pabc/6, V: volume, a: anteroposterior diameter, b:
results showed that RFA might be a promising treatment for transverse diameter, and c: longitudinal diameter).
both unifocal and multifocal PTMC (16, 17). To the best of our
knowledge, few studies about PLA for multifocal PTMC have
been reported. Therefore, this study was conducted to evaluate
the feasibility and efficacy of PLA for patients with PLA procedure
multifocal PTMC.
The patient laid on the operating table in a supine position
with the neck extended. After local anesthesia was
administered with 2% lidocaine, 0.9% normal saline was
Materials and methods carefully injected into the space between the thyroid capsule
and surrounding vital organs (common carotid artery, trachea,
Patients esophagus, and recurrent laryngeal nerve) to achieve fluid
isolation. A 21G trocar was inserted into the tumor under US
This retrospective case–control study was approved by the guidance. A 300-mm optical fiber was inserted into the trocar
ethics committee of our hospital. Twelve patients with 26 while retracting the needle by 5 mm, exposing the tip of the
PTMCs and 60 patients with 60 PTMCs were treated with optical fiber to directly contact with the tumor. The treatment
PLA in our hospital between June 2018 and September 2021. instrument was a high-power semiconductor laser that could
All the nodules were confirmed by fine-needle aspiration biopsy continuously emit Nd-YAG laser at 1,064 nm (EchoLaser X4,
(FNAB). Relevant clinical and laboratory examinations were Esaote, Florence, Italy). Ablation was suspended when the
gasification and hypoechoic areas covered and completely Analysis and statistics
exceeded the edge of the lesion by at least 2 mm, and the
area of necrosis was assessed by contrast-enhanced ultrasound Data were analyzed using the statistical software SPSS,
(CEUS) within 30 min to determine whether supplementary version 19.0. Quantitative data that conformed to a normal
ablation was needed. At the end of the treatment, the laser was distribution were described as mean ± standard deviation (SD),
turned on while the trocar needle and optical fiber were and compared by independent samples t test. Quantitative data
withdrawn together to the outside of the thyroid envelope for that did not conform to a normal distribution were described as
ablating the needle tract. For multifocal PTMC, this procedure median (first quartile, third quartile), and compared by
was first performed for one nodule and successively repeated Mann–Whitney U test. Baseline characteristics of patients,
for the other nodules. preoperative sonographic features of conventional US and
CEUS, and new lesions after PLA were compared with Fisher
test. p < 0.05 was considered to indicate a significant difference.
CEUS evaluation
Before CEUS, the background gain was adjusted to the echo Results
of thyroid capsule just displayed, and the focus was placed on the
deep surface of the target lesion. A bolus of 2.0–2.4 ml Baseline characteristics of participants
microbubble contrast agent (Sonovue, Bracco, Milan, Italy)
was injected through the dorsal vein, followed by injecting Between June 2018 and September 2021, we included 12
5 ml of normal saline. The timer was started immediately, patients with multifocal PTMC and 60 patients with unifocal
lasting for 2 min. The whole process was recorded and stored PTMC who were treated with PLA in our hospital. The baseline
on the US instrument’s hard drive. CEUS was performed to characteristics of patients and preoperative ultrasonic
evaluate the perfusion intensity of every nodule before PLA and appearances of the PTMCs are listed in Table 1. In the multi-
volume of perfusion defect after PLA. PTMC group, every patient had two to four nodules, with
unilateral tumors in five cases and bilateral tumors in seven
cases. The mean maximum diameter in the multi-PTMC group
Therapy evaluation and follow-up was smaller than that in the uni-PTMC group (p = 0.010), but
the mean volume before PLA had no difference between the two
Complications, such as pain, bleeding, and nerve damage, groups (p = 0.059). The differences in the characteristics of
were evaluated after PLA. The efficacy of local treatment was conventional US and CEUS before PLA were not statistically
evaluated by conventional US and CEUS. Conventional US was significant (p > 0.05 for all).
performed at 30 min, 2 days, 1 month, 3 months, 6 months, and The treatment parameters during PLA, follow-up time,
every 6 months after that. Conventional US mainly focused on incidence of new PTMC, and lymph node metastases after PLA
the volume of the ablated area, tumor recurrence, and are listed in Table 2. There were statistically significant differences
metastasis. CEUS was performed within 30 min and 2 days in the energy, operation time, and amount of isolation liquid
after PLA. On CEUS, the extent of non-enhanced area after between the two groups (p < 0.05 for all). The differences in the
ablation was evaluated to confirm that we had achieved a greater power, complications, incidence of new PTMC, and follow-up
volume of necrosis than that of the nodule. We considered the time were not statistically significant (p > 0.05 for all). The mean
complete ablation based on the following imaging findings: (1) follow-up durations in multi-PTMC and uni-PTMC groups were
conventional US showed the extent of the ablated area beyond 19.75 ± 11.46 months (range, 6–36 months) and 16.33 ± 10.01
the tumor border; and (2) CEUS showed the extent of the months (range, 4–40 months), respectively.
perfusion defect area significantly greater than the primary All the patients tolerated the procedure well. In the uni-PTMC
lesion. In cases which incomplete ablation was observed, a group, one patient developed a hematoma during ablation, which
complementary ablation was performed immediately. Volume did not enlarge after 10 min of local compression, and the
reduction rate (VRR) at different follow-up periods after PLA hematoma was absorbed within a week. There were no
treatment was calculated. VRR = (V30min − Vfollow-up)/V30min complications such as hoarseness, skin burns, esophageal injury,
(V30min was the volume at 30 min after PLA, and Vfollow-up was tracheal injury, or infection in both groups. The overall
the volume at each time point of follow-up). US-guided FNAB complication rates in the multi-PTMC and uni-PTMC groups
was performed for lesions when the following items occurred were 0% and 1.7%, respectively, with no significant difference (p =
during follow-up: (1) detection of insignificant reduction or 1.000). During follow-up, there were one and three new PTMCs in
regrowth of the ablated area; (2) detection of new suspicious the multi-PTMC and uni-PTMC groups, respectively. One case in
nodules in thyroid during follow-up; and (3) detection of the multi-PTMC group was located in the right lobe, while two
suspicious cervical lymph nodes. cases in the uni-PTMC group were located in the ipsilateral lobe
TABLE 1 Characteristics of patients and PTMCs between the two TABLE 2 Characteristics during and after PLA between the two groups.
groups before PLA.
Characteristics of PLA multi-PTMC uni-PTMC p-value
Characteristics Nodules/Patients, n/N (%) p-value (N = 12) (N = 60)
FIGURE 1
The diagram displayed the VRR at each follow-up after PLA.
Tumor multifocality was suggested as an independent risk preliminarily verified according to the short-term follow-
factor for the recurrence of PTC after total thyroidectomy, but up results.
the difference was significant only in those patients with PTC Although both RFA and PLA can achieve good clinical
>1 cm but not in PTMC (11). In addition, multifocality was not outcomes for PTMC, many differences exist between the two
an exclusion criterion in the active surveillance protocol for low- techniques. First, heat-acting ends of PLA and RFA should be
risk PTMC in the United States, Canada, and South Korea (32– placed at the proximal and distal end of the nodule, respectively,
34). Moreover, some studies with long-term follow-up revealed before ablation, because the direction of heat propagation is
no significant differences in tumor size increase, lymph node mainly forward for PLA and backward for RFA. Second, in
metastasis, and extra-thyroidal invasion between unifocal and contrast to RFA, the temperature around optical fiber can reach
multifocal PTMC (35, 36). Although the current guidelines for over 200°C due to the absence of a cold circulation, allowing
the thermal ablation of PTMC did not recommend ablation of complete tumor inactivation through vaporization and
multifocal PTMC, several studies had been conducted on the carbonization. Third, compared to RFA, PLA results in a
clinical outcomes of RFA for multifocal PTMC (16, 17). A large smaller area of necrosis due to limited lateral spread of heat,
cohort study evaluated the efficacy of RFA in 432 patients with which might make it safer for nodules close to the recurrent
unifocal PTMC and 55 patients with multifocal PTMC, and the laryngeal nerve or dangerous areas.
results showed that multifocality had little effect on patient In 2011, the first case of PTMC treated by PLA was reported
outcomes (16). According to the results in our study, the (5), and a 10-year follow-up study of PLA in the treatment of
feasibility and efficacy of PLA for multifocal PTMC were solitary PTMC was published in 2021 (37). In the past 10 years,
TABLE 3 Volume changes and VRR of the ablated lesions between the multi-PTMC group and the uni-PTMC group.
FIGURE 2
(A) A 33-year-old female patient had bilateral hypoechoic lesions (arrowhead), which were confirmed as PTMCs by FNAB. (B) After both the
PTMCs underwent US-guided PLA, the ablated lesions appeared as well-defined heterogeneous echogenic areas on the grayscale US, with a
central hypoechoic ablated needle channel. (C) On the final follow-up, the two ablated lesions were almost completely absorbed, leaving only
scar strips (arrowhead).
many studies of PLA for unifocal PTMC have confirmed its high inactivation. Short-term and long-term studies showed that
safety and efficacy. Valcavi et al. (38) treated three patients with PLA for unifocal PTMC had the advantages of precise ablation
unifocal PTMC by PLA followed by surgical removal of the scope, high safety, low trauma, rapid postoperative recovery, and
thyroid gland. There was no thermal damage to the muscles, low recurrence rate (6, 8, 9, 37). There were no increases in
parathyroid gland, or the laryngeal recurrent nerve. The complication rate, recurrence rate, and metastasis rate of PLA
postoperative pathology showed tissue destruction and for unifocal PTMC compared with conventional surgery (26).
charring, with no tumor cell remnants, indicating complete However, the safety, clinical outcomes, and prognosis of PLA for
multifocal PTMC have not been studied. In the present study, adequately represent differences in the safety and efficacy after
US-guided PLA was performed for unifocal PTMC and PLA treatment between multifocal and unifocal PTMC. Third,
multifocal PTMC. Tumor reduction, new PTMC, and lymph the follow-up time was relatively short, and the long-term
node metastasis after treatment were compared between the two follow-up results were uncertain due to the indolent
groups to analyze the feasibility and effectiveness of PLA in characteristic of PTMC.
treating patients with multifocal PTMC. In conclusion, short-term follow-up showed that safety and
In this study, both multifocal and unifocal PTMC were efficacy of PLA in the treatment of multifocal PTMC are similar
mainly presented as solid, non-calcified, and taller-than-wide to those of unifocal PTMC. It may be an alternative technique
nodules with low blood supply on conventional US and for patients who are not eligible or are unwilling to
moderate perfusion intensity on CEUS before PLA. As the undergo surgery.
number of lesions increased, operation time, energy, and
amount of isolation liquid significantly increased. In terms of
complications, due to the increased number of punctures and Data availability statement
prolonged operation time, the multi-PTMC group was expected
to have a higher risk of complications such as bleeding; however, The original contributions presented in the study are
there was no difference in complications between the included in the article/supplementary material. Further
two groups. inquiries can be directed to the corresponding author.
The incidence of new PTMC and metastatic lesions after
thermal ablation was about 0–5.6% (39). Bilateral multifocality
was more aggressive than unilateral multifocality, but it was not Ethics statement
an independent prognosis factor (40). In 2021, one study
preliminarily evaluated the efficacy and safety of RFA for 47 This study was reviewed and approved by Ethics Committee
patients with 100 bilateral PTMCs, and the incidences of lymph of Ruijin Hospital, Shanghai Jiao Tong University School of
node metastasis and recurrence were 2.13% and 4.26%, Medicine. The patients/participants provided their written
respectively (17), which were not higher than the currently informed consent to participate in this study.
known incidences (37, 39). In this study, we included 7
(58.3%) patients with bilateral multifocal PTMCs. No lymph
node metastasis was detected, and one patient (8.3%) developed Author contributions
a new PTMC. However, there were no significant differences in
the incidences of new PTMC and lymph node metastasis LZ is the first author for performing PLA, data statistical and
between multi-PTMC and uni-PTMC groups over the similar writing this manuscript. GPZ is a co-author for her arrangement
follow-up period. of clinical data. WWZ is a co-author for his contribution in
In our study, the volume of the necrotic area increased on revision. WZ is the correspondence author for his organization,
postoperative day 2 in both groups, which might be attributed to coordination and revision of this manuscript. All authors
the formation of microthrombi in the edematous area contributed to the article and approved the submitted version.
surrounding the necrotic site, inducing further tissue damage
after PLA. The VRRs of the two groups gradually increased after
1 month until the ablated lesions almost disappeared, and the Conflict of interest
volume change curves were similar. Thus, the absorption rate in
the multifocal PTMC group was not significantly different from The authors declare that the research was conducted in the
that in the unifocal PTMC group according to the short-term absence of any commercial or financial relationships that could
follow-up. Although multifocal PTMC was not recommended as be construed as a potential conflict of interest.
an indication for thermal ablation therapy according to the
current guidelines and expert consensus, PLA is a potentially
effective technique for multifocal PTMC according to our Publisher’s note
results. Surgery remains the first line of treatment for
multifocal PTMC. However, with full informed consent, All claims expressed in this article are solely those of the
patients who refuse or are ineligible for surgery may choose authors and do not necessarily represent those of their affiliated
PLA as an alternative treatment with strict follow-up. organizations, or those of the publisher, the editors and the
Our study has some limitations. First, this was a reviewers. Any product that may be evaluated in this article, or
retrospective study, and selection bias could not be avoided. claim that may be made by its manufacturer, is not guaranteed
Second, the sample size was small, and our results may not or endorsed by the publisher.
References
1. Fagin JA, Wells SAJr. Biologic and clinical perspectives on thyroid cancer. 22. Yue W, Wang S, Yu S, Wang B. Ultrasound-guided percutaneous
New Engl J Med (2016) 375:1054–67. doi: 10.1056/NEJMc1613118 microwave ablation of solitary T1N0M0 papillary thyroid microcarcinoma:
2. Li M, Dal Maso L, Vaccarella S. Global trends in thyroid cancer incidence and initial experience. Int J Hyperthermia (2014) 30:150–7. doi: 10.3109/
the impact of overdiagnosis. Lancet Diabetes Endocrinol (2020) 8:468–70. 02656736.2014.885590
doi: 10.1016/S2213-8587(20)30115-7 23. Cho SJ, Baek SM, Lim HK, Lee KD, Son JM, Baek JH. Long-term follow-up
3. Lang BH, Wong CK. A cost-effectiveness comparison between early surgery results of ultrasound-guided radiofrequency ablation for low-risk papillary thyroid
and non-surgical approach for incidental papillary thyroid microcarcinoma. Eur J microcarcinoma: More than 5-year follow-up for 84 tumors. Thyroid (2020)
Endocrinol (2015) 173:367–75. doi: 10.1530/EJE-15-0454 30:1745–51. doi: 10.1089/thy.2020.0106
4. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, 24. Wang L, Xu D, Yang Y, Li M, Zheng C, Qiu X, et al. Safety and efficacy of
et al. 2015 American Thyroid association management guidelines for adult patients ultrasound-guided percutaneous thermal ablation in treating low-risk papillary
with thyroid nodules and differentiated thyroid cancer: The American thyroid thyroid microcarcinoma: A pilot and feasibility study. J Cancer Res Ther (2019)
association guidelines task force on thyroid nodules and differentiated thyroid 15:1522–9. doi: 10.4103/jcrt.JCRT_214_19
cancer. Thyroid (2016) 26:1–133. doi: 10.1089/thy.2015.0020 25. Zhang M, Tufano RP, Russell JO, Zhang Y, Zhang Y, Qiao Z, et al.
5. Papini E, Guglielmi R, Gharib H, Misischi I, Graziano F, Chianelli M, et al. Ultrasound-guided radiofrequency ablation versus surgery for low-risk papillary
Ultrasound-guided laser ablation of incidental papillary thyroid microcarcinoma: a thyroid microcarcinoma: Results of over 5 years' follow-up. Thyroid (2020) 30:408–
potential therapeutic approach in patients at surgical risk. Thyroid (2011) 21:917– 17. doi: 10.1089/thy.2019.0147
20. doi: 10.1089/thy.2010.0447 26. Zhou W, Ni X, Xu S, Zhang L, Chen Y, Zhan W. Ultrasound-guided laser
6. Peng K, Zhou P. Long-term efficacy of ultrasound-guided percutaneous laser ablation versus surgery for solitary papillary thyroid microcarcinoma: a
ablation for low-risk papillary thyroid microcarcinoma: A 5-year follow-up study. retrospective study. Int J Hyperthermia (2019) 36(1):897–904. doi: 10.1080/
BioMed Res Int (2021) 2021:6616826. doi: 10.1155/2021/6616826 02656736.2019.1649475
7. Ji L, Wu Q, Gu J, Deng X, Zhou W, Fan X, et al. Ultrasound-guided percutaneous 27. Xu B, Zhou NM, Cao WT, Gu SY. Comparative study on operative trauma
laser ablation for papillary thyroid microcarcinoma: a retrospective analysis of 37 between microwave ablation and surgical treatment for papillary thyroid
patients. Cancer Imaging (2019) 19:16. doi: 10.1186/s40644-019-0204-x microcarcinoma. World J Clin cases (2018) 6(15):936–43. doi: 10.12998/wjcc.v6.i15.936
8. Zhang L, Zhou W, Zhan W, Peng Y, Jiang S, Xu S. Percutaneous laser 28. Li J, Liu Y, Liu J, Yang P, Hu X, Qian L. A comparative study of short-term
ablation of unifocal papillary thyroid microcarcinoma: Utility of conventional efficacy and safety for thyroid micropapillary carcinoma patients after microwave
ultrasound and contrast-enhanced ultrasound in assessing local therapeutic ablation or surgery. Int J Hyperthermia (2019) 36:640–6. doi: 10.1080/
response. World J Surg (2018) 42:2476–84. doi: 10.1007/s00268-018-4500-6 02656736.2019.1626492
9. Zhou W, Jiang S, Zhan W, Zhou J, Xu S, Zhang L. Ultrasound-guided 29. Shen K, Wang HA-O, Xie Y, Zhu J, Zhu C, Ren A. Inconsistent results
percutaneous laser ablation of unifocal T1N0M0 papillary thyroid microcarcinoma: between the two studies comparing microwave ablation and surgery for papillary
Preliminary results. Eur Radiol (2016) 27:2934–40. doi: 10.1007/s00330-016-4610-1 thyroid microcarcinoma. Int J Hyperthermia (2020) 37:273. doi: 10.1080/
02656736.2020.1739346
10. Zhang L, Zhou W, Zhan W. Role of ultrasound in the assessment of
percutaneous laser ablation of cervical metastatic lymph nodes from thyroid 30. Xu D, Ge M, Yang A, Cheng R, Sun H, Wang H, et al. Expert consensus
carcinoma. Acta Radiol (2018) 59:434–40. doi: 10.1177/0284185117721261 workshop report: Guidelines for thermal ablation of thyroid tumors (2019 edition).
J Cancer Res Ther (2020) 16:960–6. doi: 10.4103/jcrt.JCRT_558_19
11. Choi WR, Roh JL, Gong G, Cho KJ, Choi SH, Nam SY, et al. Multifocality of
papillary thyroid carcinoma as a risk factor for disease recurrence. Oral Oncol 31. Mauri G, Hegedus L, Bandula S, Cazzato RL, Czarniecka A, Dudeck O, et al.
(2019) 94:106–10. doi: 10.1016/j.oraloncology European Thyroid association and cardiovascular and interventional radiological
society of Europe 2021 clinical practice guideline for the use of minimally invasive
12. Wang F, Yu X, Shen X, Zhu G, Huang Y, Liu R, et al. The prognostic value of treatments in malignant thyroid lesions. Eur Thyroid J (2021) 10:185–97.
tumor multifocality in clinical outcomes of papillary thyroid cancer. J Clin doi: 10.1159/000516469
Endocrinol Metab (2017) 102:3241–50. doi: 10.1210/jc.2017-00277
32. Sawka AM, Ghai S, Tomlinson G, Rotstein L, Gilbert R, Gullane P, et al. A
13. Lin JD, Chao TC, Hsueh C, Kuo SF. High recurrent rate of multicentric protocol for a Canadian prospective observational study of decision-making on
papillary thyroid carcinoma. Ann Surg Oncol (2009) 16:2609–16. doi: 10.1245/ active surveillance or surgery for low-risk papillary thyroid cancer. BMJ Open
s10434-009-0565-7 (2018) 8:e020298. doi: 10.1136/bmjopen-2017-020298
14. Grogan RH, Kaplan SP, Cao H, Weiss RE, Degroot LJ, Simon CA, et al. A 33. Kwon H, Oh HS, Kim M, Park S, Jeon MJ, Kim WG, et al. Active surveillance for
study of recurrence and death from papillary thyroid cancer with 27 years of patients with papillary thyroid microcarcinoma: A single center's experience in Korea. J
median follow-up. Surgery (2013) 154:1436–46. doi: 10.1016/j.surg.2013.07.008 Clin Endocrinol Metab (2017) 102:1917–25. doi: 10.1210/jc.2016-4026
15. Neuhold N, Schultheis A, Hermann M, Krotla G, Koperek O, Birner P. 34. Brito JP, Ito Y, Miyauchi A, Tuttle RM. A clinical framework to facilitate risk
Incidental papillary microcarcinoma of the thyroid–further evidence of a very low stratification when considering an active surveillance alternative to immediate
malignant potential: a retrospective clinicopathological study with up to 30 years of biopsy and surgery in papillary microcarcinoma. Thyroid (2016) 26:144–9.
follow-up. Ann Surg Oncol (2011) 18:3430–6. doi: 10.1245/s10434-011-1663-x doi: 10.1089/thy.2015.0178
16. Yan L, Zhang M, Song Q, Xie F, Luo Y. Clinical outcomes of radiofrequency
35. Sugitani I, Ito Y, Takeuchi D, Nakayama H, Masaki C, Shindo H, et al.
ablation for multifocal papillary thyroid microcarcinoma versus unifocal papillary
Indications and strategy for active surveillance of adult low-risk papillary thyroid
thyroid microcarcinoma: a propensity-matched cohort study. Eur Radiol (2022)
microcarcinoma: Consensus statements from the Japan association of endocrine
32:1216–26. doi: 10.1007/s00330-021-08133-z
surgery task force on management for papillary thyroid microcarcinoma. Thyroid
17. Yan L, Zhang M, Song Q, Xiao J, Zhang Y, Luo Y. The efficacy and safety of (2021) 31:183–92. doi: 10.1089/thy.2020.0330
radiofrequency ablation for bilateral papillary thyroid microcarcinoma. Front
36. Nagaoka R, Ebina A, Toda K, Jikuzono T, Saitou M, Sen M, et al.
Endocrinol (2021) 12:663636. doi: 10.3389/fendo.2021.663636
Multifocality and progression of papillary thyroid microcarcinoma during active
18. Kim JH, Baek JH, Lim HK, Ahn HS, Baek SM, Choi YJ, et al. 2017 thyroid surveillance. World J Surg (2021) 45:2769–76. doi: 10.1007/s00268-021-06185-2
radiofrequency ablation guideline: Korean society of thyroid radiology. Korean J
37. Kim HJ, Chung SM, Kim H, Jang JY, Yang JH, Moon JS, et al. Long-term efficacy
Radiol (2018) 19:632–55. doi: 10.3348/kjr.2018.19.4.632
of ultrasound-guided laser ablation for papillary thyroid microcarcinoma: Results of a
19. Yan L, Lan Y, Xiao J, Lin L, Jiang B, Luo Y. Long-term outcomes of 10-year retrospective study. Thyroid (2021) 31:1723–9. doi: 10.1089/thy.2021.0151
radiofrequency ablation for unifocal low-risk papillary thyroid microcarcinoma: a 38. Valcavi R, Piana S, Bortolan GS, Lai R, Barbieri V, Negro R. Ultrasound-
large cohort study of 414 patients. Eur Radiol (2021) 31:685–94. doi: 10.1007/ guided percutaneous laser ablation of papillary thyroid microcarcinoma: a
s00330-020-07128-6 feasibility study on three cases with pathological and immunohistochemical
20. Lim HA-O, Cho SA-O, Baek JH, Lee KD, Son CW, Son JM, et al. US-Guided evaluation. Thyroid (2013) 23:1578–82. doi: 10.1089/thy.2013.0279
radiofrequency ablation for low-risk papillary thyroid microcarcinoma: Efficacy 39. Min Y, Wang X, Chen H, Chen J, Xiang K, Yin G. Thermal ablation for
and safety in a Large population. Korean J Radiol (2019) 20:1653–61. doi: 10.3348/ papillary thyroid microcarcinoma: How far we have come? Cancer Manag Res
kjr.2019.0192 (2020) 12:13369–79. doi: 10.2147/CMAR.S287473
21. Teng DA-O, Li HQ, Sui GQ, Lin YQ, Luo Q, Fu P, et al. Preliminary report 40. Yan TA-O, Qiu W, Song J, Ying T, Fan Y, Yang Z. Bilateral multifocality, a
of microwave ablation for the primary papillary thyroid microcarcinoma: a large- marker for aggressive disease, is not an independent prognostic factor for papillary
cohort of 185 patients feasibility study. Endocrine (2019) 64:109–17. doi: 10.1007/ thyroid microcarcinoma: A propensity score matching analysis. Clin Endocrinol
s12020-019-01868-2 (Oxf) (2021) 95:209–16. doi: 10.1111/cen.14455