Comme間臨時

The Application of 2015 America盟芷hyroid Association Ma詛ageme盟t Guidelines for Adult Patients with Thyroid Nod祖les and Differentiated Thyroid Cancer in Taiwa盟and their Association with Computer-Aided Detection

a亞dDiag盟的is System

Tien-Chul1 Challg

Abstrad

Background. The 2015 American ThyroidAssociation (ATA) Management Guidelines for Adult Pa­

tients wíth Thyroid Nodules and Differentiated Thyroid Cancer were publìshed in the Joumal “Thyroid"

recently. Although the guidelines are important and most of them are compatible with our daily prac­

tice、 some of them are not so pτactical and aJso different 白'om the reaI situation in Taiwan. The aims

of this review were to point out them, to make some comments, and also to conelate the role of the

Computer-Aided Detectlon and Diagnosis System whích was inventeιin Taiwan.

Findings. The most important difference from the real sÏtuation in Taiwan was to neglect the manage因

此lent of th)'TOid lesions smaUer than 1 cm 111 diameter, and the timing in use of 18FDG_ PET in this nεw

guideline. In addition, although the usefulness of thyroid sonography was emphasized in the evalua­

tion of thyroid nodul肘， it could be better if findings could be applied more objectively with assis­

tance 0 1' computer-aided detection and diagnosis system.

Conclusio誼. Because of the low cost of medical ser明vice in Taiwan, we consider that even for small

thyroid lesions, especially fir剖， hard步 inegular in palpation, they should be examincd and managed as

soon as possible to preserve good li1'e quality based on the ATA's recommendation for surgical man­

agement. As fo1' thyroid sonography, the new 2015 ATA guidelines remind clinicians the importance

to screen nodules by sonographic findings, and computer-aided detection and diagnosis systems can

assist to attain the goal in a more objective way to screen the patients from fine-needle aspiration cy­

tology and to save work團loading.

[Fomlos J Endocrinol Metab 6: 白，帥， 2015]

KeyJ妙。rds: th.vroid nodule, th.Yl說d neoplasms, guideline, computer-assisted diagnos坊， Tai-wαn

Department of Intemal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicin皂， Taip缸， Taiwan Correspondence to: Dr. Tien-Chun Chang, Department of Intemal Medicine, National Taiwan University Hospit祉， 7 ，

Chung-Shan South Road, Taip缸， Taiwan. Tel: +886 2 2312 3456 ext. 65034 Fax: +88622593 0146 E-mail: tienchunchang@ntu.edu.tw

53

Tien-Chun Chang

Introduction

The 2015 American Thyroid Association 。在rA)Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer

were Epub ahead ofprint on October 14, 2015 in the Journal “Thyroid" 1 Long time has passed since

the last 耳üdeline been published in 20092 • The aim of the present paper was to evaluate the feasibili句lofimplementation of the new ATA Guidelines in Tai自

wan. The author also wants to explore the clinical use of a locally-invented computer且aided detection

and diagnosis system for thyroid nodules and neo­plasms3.

Size of thyroid lesions

Most of the new guidelines are applicable in

The cost of 18pDG世PET scan is very expensive, even in a medical-price controlled countηlike Tai­wan. The National Health Insurance Authority lim圖ited the use of 18PDG_PET scan to those with thyroid

lesions which do not uptake of 1311 in Taiwan. 1n the 2015 ATA guideline, 18pDG回PET scan is strongly recommended because focal 18PDG_PET uptake

accompanied by an ultrasound-collfirmed thyroid nodule cOllveys an increased risk of thyroid call­

cer. Nevertheless, USillg other methods, which are cheaper than the 18PDG_PET scan, are also useful for

the diagnosis of thyroid cancers. Palpation, thyroid

ultrasounds, alld fine-needle aspiration (B叫A) cytol­ogy are good tools helping us for the assessments of thyroid nodules. 1t is not necessa可 to do 18PDG_

PET scans as frequelltly as the new guidel血的問心

ommellded.

Taiwan, for example, the time of check且up serumτhyroid so口ography

thyroglobulin and calcitonin levels. However, a m吋or difference was recognized between the ATA

guidelines alld our daily practice in the management of thyroid lesions smaller than 1 cm in diameter. 引Te

disagree with the notion that only nodules greater than 1 cm in diameter should be evaluated. Espe­

cially when the nodule is finn, hard and irregular

under palpation, the chance of malignancy is high, noma坑前 the size of the nodule being greater than 1

Cl11 or not4 • 1n addition, l11alignant thyroid nodules grow 企orn srnall lesions. The rnanagements of thy­

roid neoplasrns should start when the lesion is sl11all.

At this stage, the patient could only receive thyroid

lobectorny, and life-long replacement with thyroxine

is possibly not needed. The surgery could be less

damage and preservation of the pa吐e肘's life quality

could be easily. Therefore, frorn the balance of clini­

cal cost and benef泣， it is reasonable to manage the patient even when the thyroid lesion is srnall.

The timing of performance of posi個

tron emission tomography with

fluorodeoxyglucose C8FDG國PET)

Formos J Endocrinol Metab 6:刃-60 54

In the 2015 ATA Guidelines多 experts strongly recommended to use the sonographic patterns of a

nodule to guide the decision-making for diagnostic PNA (Recornrnendation 8)1. 1n the new guidelines, diagnostic FNA is recommended for (A) thyroid nodules > 1 crn in greatest dirnension with high sus­

picion sonographic pattern (s仕ong recornmendation, moderate咀quality evidence); (B) nodules > 1 cm in

greatest dirnension with intennediate suspicion sono­

graphic pattern (組﹒ong recornrnendation, low-quality

evidence); (C) nodules > 1.5 cm in greatest dirnen­

sion with low suspicion sonographic pattern (weak

recornmendation, low-quality evidence). Thyroid

nodule diagnostic PNA rnay be considered for: (D)

nodules > 2cm in greatest dimension with ve可 low

suspicion sonographic pattern (e.g. spongiforrn or

partially cystic nodules). Thyroid nodule diagnostic

PNA is not required for: (E) nodules that do not meet

the above criteria (strong recornrnendation, mod­erate-quality evidence); (P) nodules that 訂e purely

cystic (strong recommendation, rnoderate-quality

evidence). The above diagnostic algorithrn in rela-

ATA Guidelines for Thyroid CA

tion to sonographic changes, size of thyroid nodule

and FNA was summarized in Fig. 1. We acknowledge that thyr叫d sonography is

ve可 useful in the survey of thyroid nodules and cer“

vical lymph nodes. However, please keep in mind

that palpation is also important for the detection of

malignant thyroid lesions.

Computer圖aided detection and di­agnosis system

可九九三 agree that some thyroid lesÍons with special

changes do not need to do FNA5,6, such as spongi-

form configuration, cysts with colloid clots, giraffe

patte凹， and diffuse hyperechogenicity.5 However, we suggest to use computer-assisted diagnosis sys蝴

tems to help the clinicians to judge the lesion( s) in a more objective way3.

To avoid inapproproate use of FNA and to save

time of learning curve之 we have developed a com­

puter-aided detectiol1 and diagtlOsis (CAD) system to detect suspicious lesions fì'om thyroid ultrasonogra闖

phy for diagnostìc FNA. The CAD system is a joint

work of the Department of Industrial Engineering

and the Department of Surgery, National Taiwan

Uníversity.

ATA Guideline 2015

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Fig. 1 A diagnostic algorithm from the 2015 ATA guidelines for evaluation and management ofpatients with thyroid nodules based on ultrasound patterns.

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Tien-Chun Chang

First多 the observer needs to measure the central

transverse axis and the longi如dinal axis of the nod­

ule in the thyroid sonograms. Then, the computer

system wi1l calculate and display if four indicators, including micro-calcifications, hypoechoic lesion, heterogeneity, and indistinct margin, are presented in the sonograms or not. The system will suggest if

diagnostic FNA is needed for this patient after con­

sidering the size of the nodule and the numbers of

positive findings (poÍnters displayed at the right side

ofthe computer screen). This CAD system may pro­

vide an easy method to determine the necessity for

FNA.

The way to improve quality of life

Surgery is an important treatment approach for

thyroid cancer. The operation must be harmoniz­

ing with the whole treatment and follow-up plan.

In the 2015 ATA guidelines, experts discussed the

operative approach for thyroid malignancy. In the

Recommendation 35, the guidelines suggest: (A) for

patients with thyroid cancer > 4 cm, or with gross

extrathyroidal extension (clinical T4), or clinically

apparent metastatic disease to nodes (clinical Nl) or

distant sites (clinical M1), the initial surgical proce­

dure should include a near吋otal or total thyroidec圓

t切omy and gros蹈s removal of a叫11 primaη可r 恥mo叮r U1沮n址less

there are cωontraindicat討ions to this procedure (strong

r閃ec∞omme叩nd由at位lOn多 moderate-quality evidence); 但)

for patients with thyroid cancer > 1 cm and < 4 cm

without extrathyroidal extension, and without clini­

cal evidence of any lymph node metastases (cNO) , the initial surgical procedure can be either a bilateral

procedure (near-total or total thyroidectomy) 0 1' a

unilateral procedure (lobectomy). ThY1'oid lobec­

tomy alone may be sufficient initial treatment fo1'

low risk papi1lary and fo l1icular carcinomas; how­

ever, the treatment team may choose total thyroidec­

tomy to enable radioactive iodìne (RAI) the1'apy or

to enhance follow-up based upon disease features

and/o1' patient preferences (strong recommendation,

Formos J Endocrinol Metab 6:53-60 56

moderate-quality evidence); (c) If surge可 is cho­sen for patients with thyroid cancer < 1 cm without

extr前hyroidal extension and cNO, the initial surgi­

cal procedure should be a thyroid lobectomy unless there are clear indications to remove the con仕alateral

lobe. Thyroid lobectomy alone is sufficient t1'eat­

ment for small, unifocal, intrathY1'oidal carcinomas

in the absence of prior head and neck irradiation, familial thY1'oid carcinoma, or clinically detectable

ce1'vical nodal metastases (strong recommendation, mode1'ate-quality evidence ).1

Th1'ough these statements多 we know that the

authors of the 2015 ATA guidelines mentioned about

the application of thyroid lobectomy for thyroid

cancer < 1 cm without ex仕athyroidal extension and

cNO. The statements correspond to our appreciation

of early detection and treatment of thyroid cancers.

By early detection and early management, we can

imp1'ove the life quality of the patients. This ap­

proach can be done by thyroid sonography for early

detection, followed by a CAD system to determine

the necessity fo1' FNA and，直nally， performed thyroid

lobectomy for small thyroid neoplasms.

Why thyroid lobectomy can im 固

prove the patient's quality of life?

In the 2015 ATA guidelines, the authors men­

tioned that “even high-volume surgeons have a

higher overall postoperative complication rate when

performing total thyroidectomy compared with

lobectomy" (page 33).1 We endorse the new 那ide­

lines for their basic goals of initial the1'apy fo1' pa個

tients with differentiated thyroid cancer: to improve

overall and disease-specific survival, to 1'educe the

risk of pe1'sistent/recurrent disease and associated

morbidity, and to permit accurate disease staging

and risk stratification, while minimizing 仕eatment­

related morbidity and unnecessa可 therapy.l Of note, the larger the tumo凹， the more difficult for the treat­

ing physicians to achieve the goals without patient

harm, for instance, vocal cord paralysis, hypopa1'a-

ATA Guidelines for Thyroid CA

thyroidism, or pe口nanent hypothyroidism. On the

otherhand多 thyroid lobectomy can cure small thyroid

malignant lesion(s) without considerable complica­

tions. This is also the reason why we emphasize the

importance of early detection and 缸:eatment of thy­

roid neoplasms.

Case vignettes

Case 1

A 21 year圖。ld young man had a thyroid nodule

incidental1y detected at a hea1th examìnation. The

results of thyroíd sonography revealed that the thy國

roid lesion was close to the posterior capsu]e with

many micro-calcifications at the right lobe (Fig. 2).

U1trasonography-guided FNA c抖。Jogy proved the

lesion to be a papi1lary thyroid carcinoma (PTC)。

His left lobe of thyroid gland was apparently nonnal

by thyroid ultrasounds (Fig. 3). He received a total

thyroidectomy of thyroid gland thereafter. The pa­

thology of the right lobe of thyroid gland showed a

PTC, sized 2.5 x 2 x 1.8 cm and the left lobe was a

benign nodula1' goiter. Howeve1', the 1'esults of neck

lymph nodes dissection demonstrated that all four

nodes removed were positive for PT仁 He was fur­

ther t1'eated with 30 mCi of 1 13 人 then fo l1owed by

th抖。xine supplement life-long.

Case2

A 32 yea1'-old woman had a thyroi品 nodule 0.8

cm in diameter, found at right lobe by thyroid sonog­

raphy at a health check-up (Fig. 4). Her left lobe of

the thY1'oi社 gland was nonnal (Fig. 5). Ultrasonog­

raphy-guided FNA cytology revealed that the thyroid

nodule was a PTC. Right lobectomy was done. The

pathology corrfinned the diagnosis of PTC. The pa­

tient did not nee吐 to take thyroxine replacem叩t after

operation. She was well till 旦ow.

57

Conclusions

Because of the costs of medical service in Tai團

wan were controlled by the National Health Insur­

ance Authority, the spending for detection and t1'eat­

ment of thyroid cancers is largely affordable. We

consider that smalí thyroid lesions多 especially those

being firm , ha1'd, 0 1' irregula1' in palpation, should

be examined and managed as soon as possible. The

new 2015 ATA guide1ines remind c1inicians the im­

portance of screening thyroid nodules by sonogra­

phy. We further suggest tbat computer-aided diagno­

sis can e狂ectively and objectively belp clinicians to

make decisíons for diagnostic FNA.

Acknowle晶gements

The autbor thanks Mr. Kuo-Chen Huang for the

preparation of the Fig. 1.

References

1. Haugen BR多 Alexander EK, Bible KC，的

2015 American Thyroìd Association Manage­

ment Guidelines to1' Adult Patients with Thyr叫d

Nodules and Di宜erentiated Thyroid Cancer: The

Am臼ican Thyroid Association Guidelines Task

Force on Thvroid No出Iles and Differentiated

Thyroid Cancer. Thyroid 2016;26:1-133.

2. Cooper DS , Doherty GM , Haugen BI丸， et al.

Revised American Thyroid Assocìation manage­

ment guidelines for patients with thyroid nod­

ules and differentiated thyroid canceιThyroid

2009;19:1167自 1214.

3. Chang TC. The role of computer aided detectiol1

and diagnosis system in the diffe1'ential diagnosis

of thyroid lesions in ult1'asonography. J Med 01-

trasound 2015;23:177-184.

4. Gharib H , Papini E , Paschke R, et al. American

Association of Clinical Endocrinologis俗， As­

SOClaZlOne 間edici Endocrinolo餌， and European

Thyroid Association medical guidelines for clini-

Formos J Endocrinol Metab 6:53-60

Tien-Chun Chang

Fig. 2 The results of thyroid sonography of Case 1 revealed the thyroid lesion was c10se to the poste­rior capsule, and many micro-calci宜cations were noted at the right lobe.

Fig. 3 The left lobe of thyroid gland of Case 1 was near1y normal by thyroid sonography.

Formos J Endocrinol Metab 6:53-60 58

A C 唱。

.可I

O 伊A

Vd 、i

T VA -d rI OB e n

品iv

咀

GU G A T-A

4 The results of thyroid sOllography of Case 2 revealed a thyroid 110dule 0.8 cm i11 diameter at right lobe with hypoechogenecity.

Fig. 5 The left lobe of thyroid gla11d of Case 2 was 110rmal by thyroid s011ography.

59 Formos J Endocrinol Metab 6:53 “ 60

Tien-

cal practice for the diagnosis and management of thyroid nodules: executive summa月T of rec­ommendations. J Endocrinol Invest 2010;33(5 Suppl):51 國56.

5. Bonavita JA, Mayo J, Babb J, et al. Pattern rec­ognition of benign nodules at ultrasound of the

Formos J Endocrinol 且1etab 6:53 “ 60

thyroid: Which nodules can be left alone? AJR

2009; 193:207-213. 6. Chang TC. Ultrasonic features of thyroid can圍

cers and benign thyroid nodules for determining the necessity of動le needle aspiration cytology. J

Med Ultrasound 2010;18:54-61.