REVIEW ARTICLE J Korean Thyroid Assoc Vol. 1, No. 2, November 2008 분화성갑상선암에의한후두기관침습의치료 고려대학교의과대학이비인후 두경부외과학교실 정광윤, 정은재, 백승국 Management of Differentiated Thyroid Cancer with Laryngotracheal Invasion Kwang-Yoon Jung, MD, PhD, Eun-Jae Chung, MD and Seung-Kuk Baek, MD, PhD Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea Locally invasive thyroid cancer is an uncommon disease process, which carries significant morbidity and mortality. Differentiated thyroid cancer (DTC) invasion of the recurrent laryngeal nerve, strap muscles and trachea are the most common followed by invasion of the esophagus, internal jugular vein and carotid artery. Surgical resection is the primary treatment for locally advanced DTC. Although the optimal surgical approach (ranging from conservative shave excision to aggressive en bloc resection of tumor and vital structures) in patients with locally advanced DTC is controversial, a curative resection should be the goal unless complete tumor resection results in unwanted perioperative morbidity and mortality or widely metastatic disease is present. Postoperative radioiodine ablation with TSH suppression is imperative after surgical resection of locally advanced DTC. Patients with microscopic or small gross residual disease, after surgical resection, may benefit from postoperative external radiotherapy for local control of disease. Key Words: Thyroid neoplasms, Larynx, Trachea, Esophagus 서 론 연제에서는분화성갑상선암에의한후두기관의침습및기타국소침습의치료에대해기술하고자한다. 갑상선은상기도와식도에인접해있지만분화성암종이후두, 기관, 식도등을침범하는경우는드물다. 그러나분화성암종이국소침범을하게되면재발의가능성이높아지고, 심각한합병증이발생하며, 결국은환자가조기사망하게된다. 국소침범암종은대부분재발하였거나, 광범위한림파절전이가있는경우, 그리고원격전이가있는환자에서관찰된다. 대부분환자의사망은국소침범의부적절한치료에의한것이며어떤방법으로치료를하였는가에따라환자의삶의질이달라지므로국소침범한갑상선암의적절한치료는매우중요하다하겠다. 수술적절제가국소침범암종의가장중요한치료이지만, 가장적절한수술적치료방법에대해서는아직까지도논란이되고있다. 본 발생빈도 분화성암종의후두, 기관, 식도침범율은저자에따라 1 16% 로보고되어있다. 1,2) 유두상암종이주로국소침범을하며, 수질성암종은거의국소침범을하지않는다. 임상양상 나이가많은환자에서상대적으로진행된증례가많고, 성별로는국소진행된암종의경우남자에서높은발생빈도를보인다. 증상및징후로는점차크기가증가하는경부종괴 논문접수일 : 2008 년 10 월 17 일 / 심사완료일 : 2008 년 11 월 3 일교신저자 : 정광윤, 서울특별시성북구안암동 5 가 126-1, 135-705, 고려대학교안암병원이비인후 - 두경부외과 Tel: 02-920-5536, Fax: 02-925-5233, E-mail: kyjung@kumc.or.kr 101
Management of Differentiated Thyroid Cancer with Laryngotracheal Invasion 가가장많고, 상기도, 식도침범증상, 즉애성, 각혈, 호흡곤란, 연하곤란등이나타날수있다. 그러나경우에따라서는상당히진행될때까지특별한증상을호소하지않는환자도적지않게있으므로주의를요한다. 3) 침범기전 갑상선암이상기도와식도를침범하는기전은갑상선암자체가직접침범할수도있으며, 기관주변림프절로전이된암이침범할수도있다. 후두를침범하는경우갑상연골이나윤상갑상막을직접뚫고침범하거나갑상연골뒤로돌아서침범한다 (Fig. 1). 갑상연골뒤로진행한갑상선암의경우이상와를통해인두를함께침범하기도한다 (Fig. 2). 4) Shin 등은기관연골사이의섬유조직과갑상선피막이연속된조직임을조직소견을통하여증명하면서이러한연골간공간이기관침범을받기가장쉬운통로 (point of weakness) 라고하였다. 5) 수술전침범정도의평가 수술전종양의국소침범정도를파악하기위한검사로는기관지내시경검사와영상검사로컴퓨터단층촬영, 자기공명영상이필수적이다. 국소진행된갑상선암환자에서내시경검사는필수적이다. 성대마비유무의평가와더불어후두, 기관의 침범여부와침범범위, 상기도내경이좁아진정도, 식도침습유무등을평가하여수술계획을세우는데매우중요하기때문이다. 4) 예를들어기관연골막까지침범된경우와기관점막까지침범된경우의치료는다를것이고식도근육층까지침범된경우와식도점막층까지침범된경우역시치료가달라질것이다. 이러한판단에있어서내시경검사는매우중요한의미를가진다. 또한기관침범으로인하여기관절제및단단문합술을시행하는경우기관의어느부위까지얼마만큼을제거하고어떤방법을이용하여재건을시행해야하는가에대한판단에있어서도술전기관내시경검사는필수적이다. 컴퓨터단층촬영은종괴의범위와주위구조물과의관계를파악하는데많은정보를얻을수있다. 특히내시경검사로는알수없는후두및기관의연골침범여부판정에중요하다. 후두나기관침범의확실한증거로는후두, 기관연골의파괴, 기관강내및식도강내의침범등이있다. 이처럼명확한침범은아니지만침범을의심할수있는소견으로는정상적으로존재하는갑상선주위지방층 (fat plane) 의소멸이있다. 후두, 기관, 식도의침범은지방층소실이 3 cm 이상일때강력히의심할수있으며, 내경정맥, 반회후두신경등의주변에서는 3 cm 미만의지방층소실에서도침범이종종발견된다. 종괴가종격동으로연장되어있거나흉골 / 쇄골접합부이하로내려가있을때에도컴퓨터단층촬영이큰도움을준다. 그러나종격동침범정도가심하면자기공명영상이 Axial image뿐아니라 Coronal, Fig. 1. Invasion of the paraglottic space by thyroid carcinoma by extending through as well as behind the thyroid cartilage. Fig. 2. Invasion of the pyriform sinus by thyroid carcinoma extending around the posterior border of the thyroid cartilage. 102 J Korean Thyroid Assoc
정광윤외 Sagital image까지볼수있어더도움이된다. 1,2,4) 그외의검사로식도조영술 (Barium swallow evaluation) 은식도강내침범를검사하는데유용하다. 국소진행된갑상선암의수술적치료 Mayo clinic에서 1998년부터 2002년까지의환자군을대상으로국소침범암의예후를조사해본결과국소침범이있는환자군이없는군보다, 수술후미세적잔존암이남은군이완전히제거된군보다생존율이유의하게감소하였다. 6) 이는수술시종양을완전하게제거하는것이매우중요함을시사한다. 국소진행된갑상선암의수술적치료원칙은다음과같다. (1) 모든육안적종괴를제거한다. (2) 침습성이적은암종이므로넓은절제역이필요치않으며되도록정상구조물은희생시키지않는다. (3) 보조적치료를병행한다. 근육침습피대근 (strap muscle) 의침범만이있는경우예후에는영향을미치지않으며종괴와함께 en-bloc으로근육을제거한다. 3) 반회후두신경침습 (Recurrent laryngeal nerve invasion) 가장흔히침범되는구조물이다. 원발종양의침습에의하거나전이된기관식도림프절에의해서마비가발생할수있다. 3,7) 그러나술전반회후두신경마비가없고육안적신경침범이없는경우, 반드시신경을보존해야한다. 왜냐하면반회후두신경에미세적잔존암 (microscopic residual cancer) 이남아있더라도신경을절제하는경우와비교하여생존율이감소하거나국소재발율이증가하지않기때문이다. 3,7,8-16) 미세적잔존암이남는경우는반드시술후방사선동위원소치료와갑상선자극 Fig. 3. Staging of papillary carcinoma of the thyroid invading the trachea, based on histopathological extent of the invasion. (A) Stage I. Tumor extends through capsule of thyroid and abuts external perichondrium but does not erode cartilage or invade between cartilaginous plates. (B) Stage II. Carinoma invades between rings of cartilage or has destroyed cartilage. (C) Stage III. Carcinoma extends through cartilage or between cartilaginous plates into lamina propria of tracheal mucosa but does not elevate or invade epithelium. (D) Stage IV. Tumor extends through entire thickness of and expands tracheal mucosa. This is visible through bronchoscope as nodule or ulcerated mass. Vol. 1, No. 2, 2008 103
Management of Differentiated Thyroid Cancer with Laryngotracheal Invasion 호르몬억제요법을시행하여야한다. 술후미세잔존암이의심되나방사선동위원소검사에서종양의탐지가없는경우외부방사선조사를고려할수있다. 3,6,8) 술전반회후두신경마비가확인된경우에는종양과함께신경을 en bloc으로절제한다. 일측성대마비로신경절제후반대측의성대운동이정상이라면원발병소절제와더불어 medialization thyroplasty type I 을동시에시행할수있다. 양측성대마비인경우에는수술후기관절개술을시행한다. 3,6,7,9-16) 후두와기관침습 (Laryngotracheal invasion) 후두의연골막은갑상선암의침습을효과적으로방어하지못한다. 후두, 기관침습은주로직접적인종양의침습으로발생하며부분적으로기관을침습한경우보다점막안까지침습된경우에예후가불량하다 (Fig. 3). 4,7) 후두기관을침습한종양을절제할때고려해야할사항은다음과같다. 7) (1) longitudinal extent and laterality of involvement (2) depth of invasion into the tracheal wall (3) level of invasion (cervical vs mediastinum, trachea, cricoid, thyroid cartilage or larynx) (4) associated structures involved by the tumor 가장논란이되는것은면도절제술 (shave resection) 과완전절제술 (en bloc resection) 이다. 저자마다종양의침습범위가다르고, 한정된소수의예에서연구되었으며, 후향적으로 non-rancomized 연구가대부분이므로어느것이더합리적이라단정지을수는없다. 그렇지만후두나기관연골이침범되고후두, 기관강내침범이 (intraluminal involvement) 없으며모든육안적병변이제거가능한경우는면도절제술 (shave resection) 을시행하는것이완전절제술 (en bloc resection) 과비교해술후합병증은낮고, 생존율은비슷하다는보고가많아선호된다. 그러나후두, 기관강내침범이있는경우는완전절제술을시행하여야한다. 이때에도되도록정상구조물은보존하는보존적술식을선택한다 (Table 1). 3,6,7,9-16) 완전절제술후일차봉합이가능하지않은경우에는흉쇄유돌근골막판을이용한피판술로메꾸거나기관공을만든후나중에막는방법등을사용한다. 7) 기관단단문합술을시행하는경우에는장력없이봉합가능하도록충분한고려를하여야한다. 식도침습 (Esophageal invasion) 식도침습은대개기관침습과동반된다. 점막하또는점막까지침범되는경우는드물고식도의근육층까 Table 1. Surgical approaches to differentiated thyroid cancer involving the laryngotrachea Surgical approach Indication(s) Definition Comments Shave excision Window resection Vertical hemilaryngectomy Circumferential tracheal resection Total laryngopharyngectomy/ total laryngectomy Tumor adherent to trachea/perichondrium Unilateral invasion of laryngotrachea-superficial/causing airway obstruction Extensive unilateral invasion of trachea/larynx Closure with muscular or myocutaneous flaps Tracheal invasion >60% of circumferene or length up to six tracheal rings Tumor invading the posterior trachea not allowing preservation of any laryngeal function Gross tumor removed without resecting adjacent structures Partial tracheal/laryngeal resection Resection of larynx (cricoid/thyroid cartilage) Tracheal resection required when bilateral involvement of trachea or more than two thirds defect is created Resection of larynx without any laryngeal function preserved Avoids morbidity of extended resection results similar to extended resection <1/3 cricoid/trachea circumference may be resected without reconstruction Larger defects require flap coverage Up to 2.5 cm in length may be resection Goal is to preserve speech and swallowing Thyrotracheal and cricotracheal anastomosis possible Step resection is a variant of tracheal resection (laryngotracheal resection) Can be staged to reduce risk of perioperative complications Palliative surgery for decreasing the risk of airway obstruction/hemorrhage Does not prolong survival rate 104 J Korean Thyroid Assoc
정광윤외 지만침범되는경우가대부분이다. 3,7) 기관과함께침습된경우가식도단독으로침습된경우보다예후가불량하다. 식도가부분적으로침습이있는경우수술적변연만확보된다면별다른재건필요없이점막하부분을남겨두고기관의면도절제술처럼식도의근육층까지만을제거할수있다. 이때식도점막이손상되지않도록주의해야한다. 식도전층에침습이있거나둘레방향으로넓은침습이있는경우는분절절제술 (Segmental resection) 이필요하며, 일차봉합이나근피판을이용한재건술이필요하다. 절제의범위가광범위할때에는유리공장피판, 유리대장피판또는 gastric pull up 등을이용하여재건한다. 3,7,11,14) 종양의침습이너무광범위하여식도절제술이불가능하고식도협착에의한증상이있을경우에는보전적인목적으로식도확장이나 stent 삽입을고려해볼수있다. 외부방사선치료도수술할수없는환자의경우에보존적인방법으로시행할수있다. 3,7,8) 혈관침습 (Vascular invasion) 내경정맥이내경동맥보다더빈번히침습된다. 원발종양이직접적으로혈관을침습하는경우는드물고, 경부림프절의피막외침습이있는경우혈관침습과밀접한관련이있다. 종양혈전이 superior vena cava나심장까지침습하였을경우, superior vena cava syndrome 을초래하거나, 폐색전 (Pulmonary embolus) 에의한급사를초래할수있다. Supreior vena cava syndrome은종양의혈관내침습이나혈전에의하기보다는종양이외부에서압박하여발생하는경우가더욱빈번하다. 국소진행된갑상선암환자에서 Pemberton's sign ( 두경부와상지의부종, 경정맥확장, 흉부정맥을통한정맥우회, 호흡곤란 ) 이양성일때 superior vena cava syndrome을반드시의심해봐야한다. 혈관침습은술전에혈관조영제을이용한 CT scanning으로탐지할수있다. 종양의침습이나압박으로인하여혈관이확장되었거나 filling defect가있을때의심할수있다. 내경동맥의침습이의심될경우에는술전혈관촬영 (angiography) 을하여동맥의절단및재건을고려해야한다. 4,7,17) 내경정맥의침습이있는경우에는심각한합병증없이종양과더불어내경정맥을 en bloc으로절제한다. 극히드물지만양측으로내경정맥이침습되었을경우측부순환이형성될수있도록 6주간격을두고단계적으로수술을시행한다. Superior vena cava를침습하였을경우 median sternotomy나우측 thoracotomy를통하 여종양을제거할수있으며, 적극적인수술을하는이유는 superior vena cava의침습이있는경우에폐색전증과 tricuspid valve obstruction의위험이높기때문이다. 종양과혈전의제거는 cavatomy를통하여시행할수도있고, superior vena cava의분절적절제술을통하여시행할수도있다. 분절적절제술후에는 autogenous, cadevaric 또는 prosthetic graft로재건하여야한다. 내경동맥의경우대부분직접적인동맥내강내로의침습이드물어많은경우면도절제술 (shave resection) 이가능하나, 드물게내강내로의침습이있는경우에는내경동맥의결찰및 saphenous vein으로의혈관우회술이필요할경우도있다. 이럴경우에는술전에 balloon occlusion test로뇌동맥의측부순환을확인하는것이반드시필요하다. 4,7,14,17) 보조적치료 방사선동위원소치료와 TSH 억제를위한갑상선호르몬치료는재발율을낮추며몇몇저자들은생존율을연장시킨다고까지보고하고있다. 3,4,6) 특히분화성암종의고위험군환자에서는유용한것으로밝혀져있다. 동위원소치료가잔존갑상선을제거하기보다전이암을효과적으로치료하기위해서는반드시갑상선전적출술이나갑상선아전적출술 (subtotal thyroidectomy) 을시행하여야한다. 외부방사선치료의효과에대해서는아직도논란의여지가많으나, 몇몇저자에의하면미세적잔존암 (microscopic residual cancer) 이있거나 45세이상의환자이거나국소침범갑상선암 (locally invasive thyroid cancer) 에서외부방사선치료가재발율을낮춘다고보고하고있다. 3,4,6,7) 국소침범갑상선암환자에서가능한수술로완전하게갑상선암을제거한후에미세적잔존암 (microscopic residual cancer) 이있거나, 육안적잔존암 (gross residual cancer) 이존재할때외부방사선치료를시행할수있다. 또한분화도가나쁜암종의경우방사선동위원소치료의효과는의문시되므로이러한경우외부방사선치료가도움이된다하겠다. 치료방법은 40 50 Gy로 3 4주에걸쳐 15 20회를시행한다. 외부방사선치료시에 adriamycin을사용하면치료효과를높인다는보고도있다. 항암화합요법은 doxorubicin을기본으로한치료가시행되고있으나효과는극히실망스럽다. 갑상선암종에대한항암화학요법은기존치료법에불응하거나빠른임상적진행을보이는일부환자에게만제한적으 Vol. 1, No. 2, 2008 105
Management of Differentiated Thyroid Cancer with Laryngotracheal Invasion 로실시하는것이적절한것으로판단된다. 7,9) 중심단어 : 분화성갑상선암, 후두, 기관, 식도. References 1) Friedman M, Danielzadeh JA, Caldarelli DD. Treatment of patients with carcinoma of the thyroid invading the airway. Arch Otolaryngol Head Neck Surg 1994;120(12):1377-81. 2) Friedman M. Surgical management of thyroid carcinoma with laryngotracheal invasion. Otolaryng Clin N AM 1990;23(3):495-507. 3) Patel KN, Shaha AR. Locally advanced thyroid cancer. Curr Opin Otolaryngol Head Neck Surg 2005;13(2):112-6. 4) Randolph GW. Surgery of the thyroid and parathyroid glands. 1st ed. Philadepphia, Pennsylvania: Saunders; 2003. p.343-65. 5) Shin DH, Mark EJ, Suen HC, Grillo HC. Pathologic staging of papillary carcinoma of the thyroid with airway invasion based on the anatomic manner of extension to the trachea: A clinicopathologic study based on 22 patients who underwent thyroidectomy and airway resection. Hum Pathol 1993;24(8):866-70. 6) Kasperbauder JL. Locally advanced thyroid carcinoma. Ann Otol Rhinol Laryngol 2004;113(9):749-53. 7) Kebebew E, Clark OH. Locally advanced differentiated thyroid cancer. Surg Oncol 2003;12(2):91-9. 8) Brierley JD, Sang RW. External-beam radiation therapy in the treatment of differentiated thyroid cancer. Semin Surg Oncol 1999;16(1):42-9. 9) Wilson PC, Millar BM, Brierley JD. The management of advanced thyroid cancer. Clin Oncol 2004;16(8):561-8. 10) Czaja JM, McCaffrey TV. The surgical management of laryngotracheal invasion by well-differentiated papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg 1997;123(5):484-90. 11) Gillenwater AM, Goepfert H. Surgical management of laryngotracheal and esophageal involvement by locally advanced thyroid cancer. Semin Surg Oncol 1999;16(1):19-29. 12) Kim KH, Sung MW, Chang KH, Kang BS. Therapeutic dilemmas in the management of thyroid cancer with laryngotracheal involvement. Otolaryngol Head Neck Surg 2000;122(5): 763-7. 13) Machens A, Hinze R, Lautenschläger C, Thomusch O, Dralle H. Thyroid carcinoma invading the cervicovisceral axis: Routes of invasion and clinical implications. Surgery 2001;129(1):23-8. 14) McCaffrey TV, Bergstralh EJ, Hay ID. Locally invasive papillary thyroid carcinoma: 1940 1990. Head Neck 1994; 16(2):165-72. 15) McCaffrey TV, Lipton RJ. Thyroid carcinoma invading the upper aerodigestive system. Laryngoscope 1990;100(8):824-30. 16) Nishida T, Nakao K, Hamaji M. Differentiated thyroid carcinoma with airway invasion: Indication for tracheal resection based on the extent of cancer invasion. J Thorac Cardiov Sur 1997;114(1):84-92. 17) Gardner RE, Tuttle RM, Burman KD, Haddady S, Truman C, Sparling YH, et al. Prognostic importance of vascular invasion in papillary thyroid carcinoma. Arch Otolaryngol 2000; 126(3):309-12. 106 J Korean Thyroid Assoc