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대한내분비외과학회지 : 제10권제1호 Vol. 10, No. 1, March 2010 원저 소아분화갑상선암의 15 년이상의추적관찰 전주예수병원외과 김아람ㆍ성치원ㆍ박영삼ㆍ김철승ㆍ김갑태 Fifteen Years or Greater Follow-Up of Pediatric Differentiated Thyroid Cancer A Ram Kim, M.D., Chi Won Sung, M.D., Young Sam Park, M.D., Cheol Seung Kim, M.D., Ph.D. and Kab Tae Kim, M.D., Ph.D. Purpose: Thyroid cancer is rare in childhood. Although thyroid cancer is biologically more aggressive in children because of the high incidence of lymph node metastasis and distant metastasis when compared with that of adults, the prognosis is better. This study investigated the prognosis of pediatric differentiated thyroid cancer with 15 years or greater follow-up and we consider the proper treatment of pediatric differentiated thyroid cancer. Methods: From January, 1979 to December, 1994 during 16 years, 17 patients younger than 17 years old and who underwent thyroid surgery for well differentiated thyroid cancer at the Department of Surgery at Presbyterian Medical Center were retrospectively reviewed by the medical records and they were interviewed by telephone. Results: Total thyroidectomy was performed in 4 patients (23.5%), subtotal thyroidectomy was performed in 10 patients (58.8%) and lobectomy was performed in 3 patients (17.7%). The mean follow-up period was 23.5 years (range: 15 28.2 years) and recurrence was found in 7 cases (41.3%). Five cases (29.5%) showed locoregional recurrence and 2 cases (11.8%) showed distant metastasis. Postoperative radioiodine ( 131 I) therapy was done in 6 cases (35%) and 6 cases (35%) underwent radioiodine therapy as a therapeutic modality for metastasis. Conclusion: The pediatric well differentiated thyroid cancer in this study showed high rates of lymph node metastasis at the time of diagnosis and a high recurrence rate, but the prognosis was good (100% overall survival rate during the follow-up period). Therefore, total thyroidectomy, radical 책임저자 : 성치원, 전북전주시완산구중화산동 1 가 300 560-750, 전주예수병원외과 Tel: 063-230-8648, Fax: 063-230-8659 E-mail: saint071@hanmail.net 게재승인일 :2010 년 3 월 5 일이논문은 2008 년대한외과학회추계학술대회에서구연발표되었음. lymph node dissection and postoperative radioiodine therapy are considered the initial patient management. This aggressive therapeutic management can decrease of the recurrence rate and increase the therapeutic effect. A radioiodine scan and thyroglobulin can used for follow-up. (Korean J Endocrine Surg 2010;10:34-38) Key Words: Pediatric differentiated thyroid cancer, Total thyroidectomy and radical lymph node dissection, Radioiodine therapy 중심단어 : 소아분화갑상선암, 갑상선전절제술과림프절곽청술, 방사선요오드치료 Department of Surgery, Presbyterian Medical Center, Jeonju, Korea 서 소아및청소년에서갑상선암은가장흔한내분비악성종양이나일반적으로드물다 (0.2 0.5/100,000/yr). 미국의암등록소 SEER (Surveillance Epidemiology and End Results) 는연간십만명당 8.5명의발생률을보고하며 20세이하에서는약 2.1% 에서진단받는다. 이것은 2000 2004년에발생한것에대한보고이다.(1) 소아의분화갑상선암은드문질환으로, 소아에서발생하는모든악성종양중 0.5 3% 의빈도를보이고전체갑상선암중 3 10% 의빈도를차지한다.(2-5) 이것은 5세이하의나이에서극히드물고청소년기를통해빈도가증가하여 11 17세에 70% 를차지한다.(2,6) 분화갑상선암은소아와어른에서분명히다른임상양상을보이는데소아에서는 60 80% 이상에서국소적림프절전이를보이고 10 20% 에서주로폐로전이하는타장기전이를보인다.(7) 그러나, 이러한진행된국소병변및림프절침범그리고타장기전이가있음에도어른보다낮은장기유병률및사망률을갖는다. 이차이에대한기전이해명되지않았음에도불구하고전체적인소아분화갑상선암의장기예후는훌륭하다. 이에적절한내과적, 외과적치료적접근에대한논란이지속되고있다.(2,3,6,8) 예전에는수술후발생하는합병증때문에보존적치료 론 34

김아람외 : 소아분화갑상선암의 15 년이상의추적관찰 35 를하는것이주였으나현재수술후국소재발을줄이기위해갑상선전절제술및림프절곽청술을시행한후방사선요오드치료를추가하는적극적인치료를옹호하는의견이주류를이룬다.(7) 하지만아직도갑상선및경부림프절절제범위와수술후방사선요오드치료의역할에대한논란은지속되고있다. 소아갑상선암의경우질환의희귀성및장기간의추적관찰의어려움으로인해현재까지충분한연구가진행되지않고있는실정이다. 이연구는 17세이하분화갑상선암환자의임상양상및수술, 방사선요오드치료, 이에따른치료결과와 15년이상의추적관찰기간동안의재발및환자상태의평가를통해소아갑상선암환자에대한예후와치료방침에대해알아보고자하였다. Characteristics Table 1. Characteristics of the patients Total number 17 M:F 4:13 (1:3.25) Mean age (year) 13.3 (6.5 17) Table 2. Chief complaint of the patients Symptoms 방 1979년 1월부터 1994년 12월까지만 15년간전주예수병원에서분화갑상선암으로수술받은 17세이하소아환자 17예의임상양상, 수술방법과치료결과, 조직병리학적특징, 재발빈도, 수술후합병증, 방사선요오드치료유무등을살펴보았고여기에 15년이상환자들의생존기간, 재발유무, 예후등을알아보았다. 이는후향적연구결과로진 Anterior neck mass 15 (88.2%) Cervical lymphadenopathy 1 (5.9%) Dyspnea due to thyroid mass 1 (5.9%) Table 3. Surgical procedures Site Surgery Number Thyroid Total thyroidectomy 4 (23.5%) Near total thyroidectomy 2 (11.8%) Subtotal thyroidectomy 8 (47.0%) Lobectomy 3 (17.7%) Neck Ipsilateral RND (or MRND) and 4 (23.5%) contralateral jugular node dissection Ipsilateral RND (or MRND) 6 (35.4%) Jugular node dissection 2 (11.8%) Central neck dissection 2 (11.8%) 법 료기록및전화인터뷰를통하여이루어졌다. Type Table 4. Histopathology Number Papillary adenocarcinoma 11 (64.7%) Follicular adenocarcinoma 4 (23.5%) Papillary & follicular adenocarcinoma 2 (11.8%) Site Type Locoregional recurrence (5 cases) Distant metastasis (2 cases) Tortal (7 cases) 결 환자군의평균나이는 13.3세 (6.5 17세), 이중남자환자가 4명, 여자환자가 13명 (1:3.25) 이었고 (Table 1) 주증상은경부림프절종대 1예, 호흡곤란 1예를제외하고모두갑상선부위의종물로내원하였고내원당시시행한이학적검사상경부림프절종대가있었던경우는 8예 (47%) 였다 (Table 2). 수술방법은갑상선전절제술 4예, 갑상선근전절제술 2 예, 갑상선아전절제술 8예, 갑상선엽절제술이 3예였다. 경부림프절절제술및경정맥림프절절제술도 14예 (82.5%) 에서시행되었고이중갑상선피막을넘어침범한경우가 4명 (23.5%), 경부림프절전이가있는경우가 12명 (70.6%) 이었다 (Table 3). 수술후조직검사상유두상갑상선암이 11 명 (64.7%), 여포성갑상선암이 4명 (23.5%), 유두상갑상선암 Table 5. Recurrence Table 6. Interval of recurrence and metastasis Interval 9.6 years (1 16.5 years) 7.4 years (1.3 13.4 years) 9.0 years (1 16.5 years) Table 7. Postoperative RI (I-131) therapy Indication Number Dosage Number Cervical lymph node 3 (17.7%) Local (Thyroid bed) 2 (11.8%) Distant metastasis (Lung) 2 (11.8%) Total 7 (41.3%) Postoperative 6 61.7 mci (30 100 mci) adjuvant treatment Locoregional recurrence 4 73.3 mci (70 80 mci) Lung metastasis 2 150 mci (100 200 mci) 과

36 대한내분비외과학회지 : 제 10 권제 1 호 2010 Table 8. Comparison of the 1st operation and recurrence 1st operation Interval of recurrence Recurrence Treatment Total thyroidectomy with Rt. MRND* and 13.7 yrs Thyroid bed Follow up loss Lt. jugular LND Total thyroidectomy with Rt. RND and Lt. jugular LND 8.8 yrs Lt. upper jugular LN Upper neck node excision+ri therapy (80 mci) Total thyroidectomy with Rt. RND 8.2 yrs Lt. anterior jugular LN Lt. Jugular LND+RI therapy (70 mci) Subtotal thyroidectomy with Lt. RND 1.3 yrs Lung metastasis RI therapy (100 mci) Subtotal thyroidectomy 1 yrs Lt. jugular LN MRND+RI therapy (70 mci) Subtotal thyroidectomy with Rt. RND and 16.5 yrs Thyroid bed RI therapy (100 mci) Lt. jugular LND Subtotal thyroidectomy and Rt. RND 13.4 yrs Lung metastasis RI therapy (200 mci) *MRND = modified radical neck dissection; RND = radical neck dissection. 과여포성갑상선암이함께있는함께있는경우가 2명 (11.8%) 로나타났다 (Table 4). 수술후추적관찰도중재발한경우는모두 7예로경부림프절에서재발한경우는 3예, 갑상선수술부위의국소재발은 2예, 원격전이는 2예에서발견되었다 (Table 5). 재발이발생하기까지걸린시간은평균 9년 (1 16.5년) 으로국소재발은 9.6년 (1 16.5년), 원격전이는평균 7.4년 (1.3 13.4년) 이었다 (Table 6). 수술후방사선요오드치료를받은경우에는수술후보조요법으로 6예에서평균 61.7 mci (30 100 mci) 시행받았고국소재발로인해 4예에서평균 73.3 mci (70 80 mci), 원격전이로인한 2예에서평균 150 mci (100 200 mci) 를시행받았다 (Table 7). 재발한 7예의환아에대한치료는 1예에서추적관찰이소실되었고 1예에서는수술을거부하고방사선요오드치료만받았으며원격전이의 2예는방사선요오드치료를받았으며재발로인해재수술과방사선요오드치료를경험한환아는 3예였다 (Table 8). 현재까지추적관찰이이루어진예는 11예로평균추적관찰기간은 23.5년 (15 28.2년) 으로모두무병상태로장기생존중이며추적관찰이중단된 6명의환아의경우에도추적관찰이중단되기전까지평균 8.5년간 (4 14년) 생존하고있었다. 고찰 Thompson and Hay(9) 는소아갑상선암에대한임상경과와치료전략에관해연구하였다. 소아갑상선암은 90% 이상에서대부분유두상유형으로나타나고전형적으로적은용량의갑상선에서기인하더라도약 30% 에서갑상선피막을넘어암성장을한다. 또한약 70% 에서국소림프절전이가있고약 20% 에서주로폐로전이되는원격전이를보인다. 즉, 흔한침습적인성장과림프절전이, 흔한원격전 이때문에소아갑상선암의초기양상과경과는일반적으로공격적으로간주된다. 소아갑상선암의진단당시폐전이가있는경우거의항상의미있는경부림프절전이가있고이에수술후방사선요오드치료가요구된다. 하지만단지약 60% 에서만단순흉부방사선촬영으로폐질환이발견된다.(10) 수술후방사선요오드스캔은전이의증거를진단하기위한필수적인검사로잔존갑상선이경부에남아있는지여부를확인할수있고이것은분화갑상선암을가진소아환자에서적극적인갑상선절제를권고하는것을뒷받침한다. 소아갑상선암의특징이성인과다르기때문에소아갑상선암의치료전략으로좀더공격적인경우와소극적인경우로나누어지는데아직은각경우에따른전향적임상연구가없기때문에소아에서갑상선암의수술적처치즉, 갑상선및경부림프절절제범위는논란이되고있다. 하지만장기추적관찰의결과는수술의차이에도불구하고대게훌륭하다. 그러므로, 대부분의외과의사는갑상선암의국소적림프절침범이있을경우공격적인수술인갑상선전절제술과림프절곽청술이좋다고주장한다. 이것은대부분종양의국소조절을얻을수있는성공적인방법이다.(11-14) 게다가전체적인갑상선절제는방사선요오드를흡수하는잔존종양과경쟁하는정상갑상선조직이적기때문에보조적인방사선요오드치료를좀더효과적으로만들고갑상선이모두제거될경우혈중타이로글루불린 (thyroglobulin, Tg) 측정이종양재발의측정인자로사용될수있다. 소아갑상선암의접근에대한다른논쟁은경부절제의범위와역할이다. 경부절제술은촉지되는전이성경부림프절이있을때적응이되며진찰시에촉지되지않고영상의학적검사에서림프절종대등이없는환아에서의예방적경부절제에대한효과는증명되지않았다.(15) 표준치료적경부절제는변형근치적경부림프절곽청술을포함

김아람외 : 소아분화갑상선암의 15 년이상의추적관찰 37 한다. 수술후남아있는기능성갑상선조직의파괴를위한방사선요오드 ( 131 I 30 150 mci) 치료는특히 16세이하의환아에서수술후 4주에권유된다.(16) 갑상선전절제술및수술후방사선요오드치료를받은환자는추후정기적인타이로글루불린의추적관찰이요구되며매년진단적 131 I 전신스캔이필요하다.(17) 변형근치적경부절제술은커진림프절이있어국소적전이의존재를시사할경우에시행되는데육안적으로보이는림프절을가능한만큼제거해야한다. 국소진행된질환을가진환자에서는종양재발의위험을낮추기위해방사선요오드스캔이필수적이며이를통해재치료가가능할정도로갑상선을제거해야한다. 회귀후두신경을침범한경우신경의잔존종양은방사선요오드로치료될수있기때문에신경을희생시키면서까지절제하지않는것이좋다. 하지만다른연구에서는소아분화갑상선암은상대적으로통증이없고생존율도명백히갑상선절제의범위와관계가없기때문에소극적인갑상선절제를해야한다는주장도있다.(18,19) 게다가, 소아에서주된수술합병증은갑상선전절제술에관련된것으로주된위험은잠재적인후두신경마비및부갑상선기능저하증이다. 성대기능의저하-쉰목소리에서무성까지-는수술받은소아의 10% 이상에서일어난다. 소아갑상선암환자의 12% 이상에서수술후부갑상선의손상으로인한저칼슘혈증이발생하였다. 부갑상선호르몬결핍및이로인한저칼슘혈증은이상감각및근수축을야기할수있다.(20,21) 이런합병증들은최근의임상연구에서는과거보다는드물게일어나는것으로보고된다.(12) 방사선요오드치료는약 30% 내에서일시적인침분비저하및미각방해를일으킬수있고 (20) 드물게영구적인구강건조증도일어난다. 그리고, 방사선요오드주입첫날의오심은흔하게발생하는부작용이다. 가장심각한장기부작용으로는방사선유도백혈병으로환자의약 1% 에서일어난다. 미만성폐전이가있거나집중적인방사선요오드섭취를한소아와청소년에서는약 1% 내에서폐섬유화가일어날수있다.(20) 그리고청소년과젊은성인에서방사선요오드는정자의질을손상시켜불임을유발할수있어반복된고용량치료의경우에는정자은행을이용하는것을고려해야한다.(22) 소아갑상선암의명백히공격적인경과에도불구하고치료결과는양호하다. 소아와청소년의암관련사망률은 1% 의범위이다. 그리고상대적으로흔한종양재발은수년또는수십년후에일어나는데이는장기추적검사로우연히발견하게된다. 그러므로, 평생동안경험있는병원에서집중적인추적관찰이적극적으로권고된다. 재발의경우완전관해의이차적유도를위해수술이나방사선요오드치료를반복해야한다. 방사선요오드스캔은대부분의경우수술후남은갑상선조직의제거를위해방사선요오드치료를하고추후잔존전이성질환의관리를위해필수적으로필요하다.(12) 새로운병변의재발에대한분석을위해진단적방사선요오드스캔이매년반복되어야한다. 최근에타이로글로불린은잔존또는전이성갑상선암의유용한표지자임을보여주고있는데매년이단백의혈장농도를측정하고이수치가증가될경우재발성질환을의심할수있다.(23) 이검사의진단적정확성은잔존갑상선조직을가진환아가갑상선호르몬보충을하는경우에의미있게감소하며타이로글로불린측정의민감도는잔존또는재발갑상선암에서증가한다. 갑상선자극호르몬은의인성갑상선기능저하증의유도나재조합인간갑상선자극호르몬의복용에의해증가될수있다.(24) 본연구에서도수술방법과상관없이장기생존율이좋았으며수술합병증도적었다. 원격전이는평균 7.4년에서발생하였는데두경우모두에서폐전이였다. 이환자들모두방사선요오드치료후완전관해를보였다. 아직은전향적연구가없음으로인하여소아분화갑상선암의수술적처치의고정된권고안을만들기는어렵다. 그러나, 최근에는좀더공격적인절제를하는것이선호된다.(24) 그래서외과의사와소아내분비의사들은전또는근전갑상선절제와수술후에방사선요오드치료를통한잔여갑상선제거, 장기억제타이록신치료와의결합을많이권고하고있다. 이연구의제한점으로는적은환자군에서진행되었고장기추적관찰에따른추적관찰중단이많았으며후향적연구로인해자료수집의제한이있었다는것이다. 하지만소아갑상선암에대한추적관찰이부족한현실에서이연구를토대로하여앞으로소아갑상선암에대한좀더많은관심과다양한치료적접근이필요할것으로생각된다. 그리고, 대량의환자군에서장기추적관찰이필요하며방사선요오드치료의적정한용량및그에따른효과에대한더많은연구가필요하다. 결론소아에서분화된갑상선암은진단당시부터높은경부림프절전이및원격전이율이높은진행된양상을보이므로공격적인치료가필요하다. 하지만어른에비해장기예후가좋아수명에큰변화가없다. 수년또는수십년후에서재발이발생하는경우가많으므로어른에비해상대적으로지속적이고잦은장기적인추적관찰의중요성이강조된다. 숙련된외과의사는수술후합병증에대한큰위험없이보다공격적인갑상선전절제술및근치적경부림프절절제술을통해수술후재발률을낮출수있으며방사선요오드치료의효과를증대시킬수있다고생각된다. 또한수술

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