대한내과학회지 : 제 75 권제 4 호 2008 종설 (Review) 폐암진단에서기관지내시경의최신정보 서울대학교의과대학내과학교실, 의학연구원폐연구소 양석철 Updates in diagnostic bronchoscopy for lung cancer Seok-Chul Yang, M.D. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Lung Institute, Seoul National University College of Medicine, Seoul, Korea Despite therapeutic advances with minimally invasive surgical techniques, improved radiotherapy dosing with 3-dimensional planning, new chemotherapy agents and targeted therapies including epidermal growth factor receptor tyrosine kinase inhibitor, monoclonal antibody and anti-angiogenesis agents, the 5-year overall survival for lung cancer has remained relatively poor, mainly because by the time a diagnosis is made, lung cancer is often well advanced and treatment options are limited. The majority of lung cancer cases are diagnosed in a late stage, when nonspecific symptoms such as cough, dyspnea, and hemoptysis are present. Advances in early diagnostic and treatment options have the potential to manage lung cancer. The diagnostic approach to lung cancer may be divided into two problems; first, establishing the diagnosis and second, accuracy of staging. Bronchoscopy is now being used increasingly in the investigation and management of a wide spectrum of malignant, infectious, inflammatory, and other diseases or pathology of the lungs. There have been recently advances in bronchoscopic diagnosis of lung cancer; autofluorescence bronchoscopy, endobronchial ultrasound, and electromagnetic navigation bronchoscopy. Autofluorescene bronchoscopy exploits the inherent fluorescence property of cancerous tissue and improves detection of premalignant lesions not seen with white light bronchoscopy. Endobronchial ultrasound utilizes a flexible ultrasound probe to image and biopsy lesions and lymph nodes beyond the wall of the bronchus. Electromagnetic navigation bronchoscopy combines virtual bronchoscopy, three-demensional CT images, and a steerable probe to help navigate a bronchoscope to a particular peripheral lung lesion or lymph node. The purpose of this review is to describe current bronchoscopic advances in diagnosis and staging of lung cancer. (Korean J Med 75:398-406, 2008) Key Words: Autofluorescence bronchoscopy; Endobronchial ultrasound; Electromagnetic navigation bronchoscopy; Lung cancer; Staging 서론폐암의뚜렷한원인으로알려진흡연이암의발생및진행에중요한역할을한다는것이알려진이후에 1-3) 폐암의진단과치료방법의꾸준한발전에도불구하고 4, 5) 5년생존율이 15% 를넘지못하는데이는대다수의환자들이진단당시수술적치료를할수있는병기를넘어서늦게진단되 고있다는점이문제로대두되고있다. 폐암은전세계적으로암으로인한사망률 1위원인으로, 매년 1백 10만명의폐암환자가새로이발생하여전체암발생의 13% 를차지하고매년약 1백만명이사망한다. 또한 2006년미국내에서 1년에 173,000명의환자가새로이진단되었으며암환자사망중 28% 를차지하였다 6). 우리나라도예외는아니어서 2005년사망원인통계연보에따르면우리나라전체사망 - 398 -
- Seok-Chul Yang: Updates in diagnostic bronchoscopy for lung cancer - Figure 1. Principle of autofluorescence. Effect of the thickened epithelium of pre and early malignant tumors on excitation light (blue: solid arrow line) and the fluorescent light (green: small dotted arrow line, red: thick dotted arrow line) emitted from the submucosa. M, mucosa; Sub, submucosa; CIS, carcinoma in situ. 자 24만 5,511명중 26.7% 가암으로인해사망하여전체사망자 4명중 1명이상이암으로사망하였고, 그중가장많은암종은폐암으로전체암으로인한사망의 21.1% 를차지하였다 7). 폐암의진단에서중요한두가지요소는첫째, 암의조기진단, 둘째이의정확한병기판정으로, 폐암위험군환자를대상으로시행하는저선량흉부전산화단층촬영을포함하여새로운기관지내시경검사의발달로인해이러한문제를해결하려는노력이증가하고있다. 폐암진단에서흉부전산화단층촬영 (computed tomography, CT), 양전자단층촬영 (positron emission tomography, PET) 등의영상진단이중요한역할을하였는데진단시낮은민감도, 낮은특이도 (CT), 또한너무많은위양성 (PET) 등의문제점을안고있다. 본종설에서는폐암의진단과병기판정에서중요한발전을이룬새로운기관지내시경술 ; 자가형광기관지내시경 (autofluoresence bronchoscopy, AFB), 경기관지초음파 (endobronchial ultrasound, EBUS), 전자기유도기관지내시경 (electromagnetic navigation bronchoscopy, ENB) 에대해서자세히살펴보도록하겠다. 자가형광기관지내시경 (Autofluoresence bronchoscopy, AFB) 폐암진단에일반적으로사용되는백색광기관지내시경 (White Light Bronchoscopy, WLB) 은전암성병변 (premalignant lesion) 이라고알려진이형성증 (dysplasia) 나상피내암 (carcinoma in situ, CIS) 를진단하는데어려움이있는데이러한단점을보완하기위해서개발된것이 AFB이다. AFB는 1992년 Lam et al 8) 등에의해처음소개되어중심기도점막 의영상을얻을수있게되어 1998년처음으로 Light-Induced Fluorescence Endoscopy(LIFE) device (Xillix Technologies; Vancouver, BC, Canada) 가임상에사용되기시작하였다. 이는기관지내시경을통해특별한파장의빛을보내어기관지조직에서반사되는빛을다시모은뒤스크린으로비취게된다. 이때녹색은정상자가형광이되고적갈색은자가형광이떨어진것으로이는상피세포가두꺼워졌거나대사상태및암의신생혈관형성 (neovascularity) 이증가하므로인해야기되는현상으로 AFB 검사에서전암병변이나조기암병변을나타낸다 9) ( 그림 1). AFB 검사가중요한이유는중심기관지계의점막대부분이폐암의 17~29% 를차지하는편평세포암의시발점이될수있고 10) 중심기도의초기병변이 WLB에의해서발견되기가어렵다는현실에있다. 1. 원리빛이물체에부딪치면일부는흡수 (absorption), 산란 (scattering) 된뒤반사하게되어육안에보이게되는데인체조직에빛이비취어지면빛의양성자 (proton) 가그표면에서반사되거나산란, 흡수또는조직형광을내게된다. WLB 는똑같은파장의빛이발사되어반사되는영상을얻게되는것이고 AFB는발사되는빛의파장이반사되어되돌아올때변화되어이의변화를감지하는것이다 11). 모든생물학적조직은자외선 (ultraviolet) 또는가시광선 (visible light) 에대해서형광을발하게되는데이렇게자연적으로발현하는형광으로인해자가형광 (autofluorescence, AF) 라는용어가사용되게되었다 12). 조직형광은일반적으로육안으로는감지할수없는데 computer algorithm 과 optical filter의도움으로조직에서발현되는형광을감지할수있게된다 11). 전암성병변과기관지암병변은정상조직에비해서자가형광이떨어지게되어발견할수있으며또한 400~420 nm의보라색또는청색으로조직이 excite되면조직에서발현되는형광이정상조직과달라져서암조직에청색빛을비추게되면적색형광이녹색형광보다더많아지게된다 13, 14). 이형성증, 상피내암, 미세침습암종 (microinvasive carcinoma) 에서는정상조직에비해서약간떨어지는적색및보다더미약한녹색형광을나타내게된다 13, 15). 2. AFB systems 현재 4 종류의 system이있는데처음으로사용되기시작한 Xillix Light Induced Fluorescence Endoscopy (LIFE), 처음으로레이저를사용하지않은 Karl Storz D-Light, 이외에 - 399 -
- 대한내과학회지 : 제 75 권제 4 호통권제 578 호 2008 - Table 1. Autofluorescence bronchoscopy in intraepithelial lesions (dysplasia and carcinoma in situ) Study Patients No Sensitivity (%) Specificity (%) WLB WLB+AFB WLB WLB+AFB Lam et al 17) 94 48 73 94 94 Lam et al 18) 223 39 79 91 87 Khanavkhar et al 19) 243 28 78 84 59 Thiberville et al 20) 138 57 84 72 48 Ikeda et al 21) 158 58 92 62 66 Sato et al 22) 64 45 69 57 32 WLB, white light bronchsocopy; AFB, autofluorescence bronchoscopy Table 2. Indications of autofluorescence bronchoscopy (American College of Chest Physicians evidence-based clinical practice guideline) 1. For patients with severe dysplasia, CIS or carcinoma in sputum cytology but with chest imaging studies showing no localizing abnormality, standard WLB is recommended. AFB should be used when available (recommendation grade, IB) 2. For patients being considered for curative endobronchial therapy to treat CIS in centers where it is available, AFB may be considered to guide therapy (recommendation grade 2C) 3. For patients with known severe dysplasia or CIS in the central airways, standard WLB is recommended at periodic intervals (3-6 months) for follow-up. AFB should be used when available (recommendation grade 2C) CIS, carcinoma in situ; AFB, autofluorescence bronchoscopy Pentax System of Auto-fluorescence Endoscopy (SAFE) 1000 및 Richard Wolf Diagnositic AutoFluorescence Endoscopy (DAFE) system 이있다. 모두 AF를자극하기위해서청색 light를사용하지만 light delivery 및 capture system은각각다르다. 최근에는 Xillix에서 Onco-LIFE R 라는새로운 system이개발되어사용중이며 Pentax SAFE 3000 system은처음으로 video bronchoscope system을사용하는 AFB를개발하였다. 3. 유용성 AFB 목적은중심기관지에서발생하는편평세포폐암의조기발견에있는데여러연구에따르면암병변을진단하는데 WBL보다월등한우수성을보여주었는데 ( 표 1) 173명환자의 700개다른병변에대해시행한다재기관연구에서 AFB 검사가 WLB 보다중등도이형성증, 중증이형성증, 상피내암, 침습암종등을발견하는데상대민감도 2.71로더높은성적을거두었고 8), 그이후 AFB는미국, 유럽, 캐나다, 일본등에서다양하게사용되고있다 15, 16). 그러나이러한연구에서도생존율에대한영향력은정확히평가되지않고있다. 일반적으로 AFB는객담세포진검사결과중등도이형성증, 중증이형성증, 상피내암, 침습암종을보이는환자에서 병변의위치를확인하기위해서시행되는데 22) 임상적인적응증은 (1) 의심스러운객담세포진검사를보일때 (2) 방사선검사에서암이의심될때 (3) 만성폐쇄성폐질환자에서새로운호흡기증상이나타날경우선별 (screening) 검사 (4) 라돈 (radon), 우라늄 (uranium), 석면 (asbestos) 등의직업적노출이많을때 (5) 폐암의임상병기판정때 (6) 경기관지시술또는수술을계획할때병변의범위를알아볼때 (7) 폐암수술후경과관찰 (8) 두경부편평상피세포암의경과관찰 (9) 경기관지치료후치료성적을판정할때등다양한데최근에는 American College of Chest Physicians (ACCP) 2007년 evidence based clinical practice guideline 23) 에따라서시행하도록권장한다 ( 표 2). 4. 결론 AFB는이형증, 상피내암, 초기침습중심폐암 (early invasive, central lung cancer) 의조기진단을향상하는검사로서 WLB를대체하는것이아니라추가적인검사로서의의미가크다. AFB 검사의이환율은 WLB와비슷하고, 완치를할수있는중심기관지의전암병변을조기진단하는안전하며비교적비침습적인검사방법이다. 아직은낮은민감도와높은위양성, 검사비용의상승등의문제점이있지만 - 400 -
- 양석철 : 폐암진단에서기관지내시경의최신정보 - Table 3. Endobronchial ultrasound in staging of lung cancer Study Patients Sensitivity Specificity Accuracy number (%) (%) (%) Yasufuku et al 6) 70 95.6 100 97.1 Rintoul et al 34) 18 85 100 89 Yasufuku et al 32) 102 76.9 55.3 60.8 A B Figure 2. (A) Tip of the ultrasound puncture bronchoscope (CP-EBUS, Olympus XBF-UC260F-OL8) with the linear curved array ultrasonic transducer. (B) The balloon attached to the tip of the bronchoscope is inflated with normal saline and a decicated 22-gauge tranbronchial needle aspiration needle is inserted through the working channel to perform EBUS-TBNA. Reprinted with permission 29). 적절한임상적응증을바탕으로전암성병변을포함한조기폐암의진단과치료에도움이될수있다고판단된다. 경기관지초음파 (Endobronchial ultrasound, EBUS) 내시경초음파는처음식도벽밖의병변에대한검사및조직채취에사용되었는데 1992년처음으로기관지내시경에도입되었다 24), 제 1세대 EBUS 는 flexible miniatureized 20-MHz radial probe (UM-BS20-26R, Olympus, Japan) 을사용하였는데그끝에물로채울수있는풍선 (balloon) 이달려 있어서 ultrasound transducer와기도벽사이에공간을물로채우게되어공기로인해초음파영상이불분명하게되는단점을막아주어기관지벽과주위구조물의정밀한영상을얻을수있었다 26). Probe는풍선안에서빠르게회전하여 360 도시야를확보할수있어풍선이기관지내표면을닺는부위어느곳이나깊이 2 cm까지기관지내벽의영상을얻을수있다. 이러한장점으로인해종격동및폐문부림프절을영상화할수있게되어 EBUS 를통한폐암의림프절병기판정에서경기관지세침흡인술 (tranbronchial needle aspiration, TBNA) 의성공률을높이게되었다 27). 최근에는 ultra-mininature radial probe (UM-S20-20R, Olympus, Japan) 을이용하여말초폐결절을발견하는데이용되고있으며 28) catheter sheath를사용하므로 EBUS 가말초폐결절의조직검사때 guidance로서투시검사 (fluoroscopy) 를대체해보려는연구가있다 30). Paone et al 31) 등은직경이 3 cm 이상인말초폐결절의경우기존에사용하던일반적인경기관지조직검사와비교하여 ( 큰병변시민감도 0.77, 작은병변시 0.31) EBUS 검사할때민감도 0.83, 3 cm 이하시민감도 0.75를보인다고보고하였다. 이러한제 2세대 ultra-miniature 20-MHz radial probe (UM-S20-20R, Olympus, Japan) 은말초폐결절을발견하기위하여개발되었는데외경이 1.4 mm로 probe는 guide sheath (GS) 안에놓여져 2.0 mm working channel의굴곡성기관지경을통하여 GS-covered probe를말초병변까지접근시켜그병변의영상을얻고이후 probe를제거한뒤 GS를통해 biopsy forcep 또는 brush를가지고조직을얻어진단하게된다. 그러나제 1, 2세대 EBUS 의 probe로서는실시간으로초음파영상유도를할수없는단점이있었는데 2004년새로운 7.5-MHz convex probe EBUS (XBF-UC260F- OL8) (CP- EBUS) ( 그림 2, 3) 가일본에서개발되고 30) 이를이용한 EBUS-TBNA 가종격동또는폐문부림프절의조직학적검사에유용하다는많은연구보고가있다 6, 32, 33). Radical probe 또는 convex probe를사용한경기관지세침흡인술은안전한시술로서 Herth et al 27) 등은초기 radial probe를가지고종격동림프절이상을보이는 200명을대상 - 401 -
- The Korean Journal of Medicine: Vol. 75, No. 4, 2008 - A B Figure 3. Endobronchial image (A) and radial probe EBUS scan (B). (A) Endobronchial image demonstates a superficial tracheal tumor (arrow). (B) Radial EBUS image showed the six distinct layers. There was no invasion to the cartilage layer (arrow). Reprinted with permission 29). 으로, 기존에사용하던 TBNA 를시행한군과 EBUS-TBNA 시행한군을비교하였을때기관용골밑 (subcarinal) 림프절을제외하고모든림프절에대한검사결과전통적인 TBNA 방법보다 EBUS-TBNA 에서더높은민감도를보인다고발표하였다. Rintoul et al 34) 등에의한소규모연구에서 EBUS- TBNA 의전체민감도 0.85, 특이도 1, 정확도 0.89를나타내었다. CP-EBUS도안전하고실시간영상유도가가능하다는추가적인장점을가져서진단민감도를향상시키게되었는데 Yasufuku et al 32) 등의연구에서양성및악성질환의감별에높은민감도 (95.7%) 와특이도 (100%) 를보여주었다. 최근 Yasufuku et al 6) 등은폐암에대한병기판정을하는데 contrast enhanced CT, PET, real time CP-EBUS-TBNA 의성적을비교하였는데 EBUS-TBNA 가높은민감도 (92.3%), 특이도 (100%), 정확도 (98%) 를보여 CT (76.9%, 55.3%, 60.8%), PET (80%, 70.1%, 72.5%) 보다좋은결과를보였다 ( 표 3). 그러나 EBUS-TBNA 검사가 90% 이상의민감도를보이고있지만종격동경검사와 EBUS-TBNA 를직접비교한대단위연구가없는실정으로최근진행중인연구결과에의하면 EBUS-TBNA 의민감도 (76.9%), 특이도 (100%), 정확도 (90.9%) 를보이고종격동경검사는각각 84.6%, 100%, 93.9% 를나타내었고, EBUS-TBNA 에서심한합병증을보이는경우는없었다. 따라서이러한결과에의해서폐암의병기판정에서 EBUS-TBNA 가기존에시행되었던종격동경검사의횟수를줄일수있지않을까전망되지만미세암전이의가능성등의이유로 EBUS-TBNA 가종격동경검사를완전대치할지 는뚜렷하지않다 35). 1. 적응증 CP-EBUS의적응증은 : (1) 폐암환자에서림프절병기결정 (2) 폐암의진단 (3) 원인이불분명한폐문부, 종격동림프절종대 (4) 종격동종괴등의진단등이다. 기관지를따라있는종격동림프절 36) (1R, 1L, 2R, 2L, 4R, 4L, 7) 은 CP-EBUS에의해접근이가능하지만대동맥밑 (subaortic), 식도곁 (paraesophageal) 림프절 (5, 6, 8, 9) 은 CP-EBUS로볼수없다. CP-EBUS tip 외경이 6.9 mm이므로 10, 11 폐문부림프절은접근이가능하고엽림프절인 12은접근이어렵다. 2. 결론폐암의병기판정에서림프절의정확한병기결정은환자의예후에직접적으로영향을미치게되는가장중요한요소중의하나이다. 새로운 ultrasonic puncture broncoscope 를사용하는 EBUS-TBNA 는안전하고높은진단율을보이고종격동및폐문부림프절의조직학적접근이가능하게되어보다폐암의보다정확한병기를판정할수있어서불필요한종격동경검사를피하고알맞은폐암치료방법의선택이가능하게되었다. 앞으로종래의기술과비교하여 EBUS-TBNA 가진단적효율성이높다는것을밝혀이러한새로운양식의가치를높이는노력이필요하겠다. - 402 -
- Seok-Chul Yang: Updates in diagnostic bronchoscopy for lung cancer - Figure 4. The steerable probe with bronchoscope. Reprinted with permission 43). Figure 5. The registration screen layout in electromagnetic navigation system. Reprinted with permission 43). 전자기유도기관지내시경 (Electromagnetic navigation bronchoscopy, ENB) 실제진단이필요한폐병변으로조직검사기구를유도하는능력이떨어진다는한계로인해굴곡성기관지내시경검사의진단성공률은병변의크기와위치에따라크게좌우된다 37, 38). 굴곡성기관지내시경의진단율은 20~84% 로병변크기가반경 2 cm 이하일경우폐의바깥쪽 1/3에위치하는말초병변의진단율은 14%, 내부 2/3에위치할경우 31% 밖에되지않는다 39). 최근에말초폐질환의조직을얻는데실시간유도가가능한새로운개념의기관지내시경이개발되었는데 ENB (super Dimension Ltd, Hertzliya, Israel) ( 그림 4, 5, 6) 는영상유도탐지시스템 (image-guided localization system) 으로환자를 electromagnetic board위에눕히고 microsensor probe를기관지내시경 working channel를통해서기관지내부로전진시키게된다. Sensor가 electromagnetic field안에위치하면 sensor의위치, 방향이확인되어모니터로전송된뒤이전에얻어진 CT 영상과겹치게 (superimposed) 된다. 이러한영상유도탐지기구는기관지내에위치하는조직을얻고자미리결정된목표물로유도하여조직학적진단을하는데그목적이있다. 원리는처음에는환자의 CT scan으로부터 digitalized information이전자기유도시스템 (electromagnetic navigational system) 으로전송되어여기서흉부의 axial, coronal, sagittal views 및 virtual endoscopy image 가재구성된다. 궁극적으로는해부학적주요지점 (anatomical landmarks) ( 주로주기관지가분지되는부위 ) 가 Figure 6. The navigation screen layout in electromagnetic navigation system. Reprinted with permission 43). 각각의 CT scan 및 virtual bronchoscopy image (planning) 에서좌표화되어확인된다 ( 그림 6). 실시간기관지내시경중에 CT data 와실제구조를연관시기기위해이전작업때사용한같은확인이가능한 landmarks를확인, 저장하는데이를 registration ( 그림 5) 라고하며이와동시에 navigation system 에기록되게된다. 이러한영상유도탐지시스템은세가지로구성되는데 (1) planning software (digital image 와 CT에서얻어진 medicine standards -DICOM- image communications을 3차원재구성과기관지의 virtual bronchoscopy와함께 multiplanar images로전환 ) (2) 위치확인 sensor가있으며방향전환이자유자재인 eight-way steerable probe ( 그림 4) (3) planning - 403 -
- 대한내과학회지 : 제 75 권제 4 호통권제 578 호 2008 - data를가지고있는컴퓨터와연결된 field generator인 electromagnetic board 등이있다 40-42). 2003년처음으로예비조사 (pilot study) 가진행되었고, 일부대조군없이시행된연구에서시술과정이안전하고이전의기관지내시경때소요되는시간에비교해서평균 15분정도밖에더소요되지않았고환자의 69% 에서성공적인진단적조직증명이가능하였다 41). 이후연속된연구보고에의하면 100% 에서목표한병변에도달할수있었고, 80.3% 40, 41) 에서진단을얻을수있었다 ( 이중말초병변에서는 74%, 림프절은 100% 에서진단되고반경이 2 cm 이하일경우 57% 에서진단을얻을수있었음 ). 1. 적응증 ENB는폐암진단및병기에중요한역할을할수있는데우선적으로말초폐병변의조직학적진단에이용될수있고더불어종격동및폐문부림프절의조직학적접근에사용될수있다. 이외에도가능성이있는여러적응에대해서여러임상연구가진행되고있다 41, 43-45). 2. 결론 ENB는안전하고말초폐종괴의진단에유용한방법이다. 기존의기관지내시경에비교하여 ENB를이용할경우말초병변에대한진단율이월등히높으며또한투시경검사와비교하여방사선노출이없다는장점이있다. 앞으로폐암의조기진단과치료에중요한역할을할것으로판단되나이러한방법이널리임상에이용되기전에 navigational accuracy를향상시키기위해 navigation sensor와소프트웨어 (software) 의발달이필요하고기존에이용되던 EBUS 와비교하는연구도필요할것으로판단된다. 결 폐암의진단과치료에서많은발달이있었는데도불구하고 5년생존율이 15% 를못미치는상황에서새로운기관지내시경술, 즉자가형광기관지내시경, 경기관지초음파, 그리고전자기유도기관지내시경등의발전은폐암을보다정확하고빠르게진단하고, 알맞은치료선택을결정하기위해필수적인폐암의병기판정에중요한역할을할것이다. 자가형광기관지내시경은중심기관지의조기폐암의진단에중요하고 CP-EBUS는종격동림프절을접근할때, 그리고전자기유도기관지내시경은종격동림프절병기판정및폐말초질환의진단에중심적인역할을할것이다. 론 아직까지는어떤검사가월등하고어떤추가적인검사가필요한지에대한연구가부족하지만이러한새로운기관지내시경의진보를통해보다다양한방법으로폐암환자에게접근할수있게되었다. 앞으로효과비용적인면에서어떻게이런검사방법들을적절히사용할지에대한추가연구가필요할것으로판단된다. 중심단어 : 자가형광기관지내시경 ; 경기관지초음파 ; 전자기유도기관지내시경 ; 폐암 ; 병기 REFERENCES 1) Alberg AJ, Smet JM. Epidemiology of lung cancer. Chest 123:21S-49S, 2003 2) Thun MJ, Henley SJ, Calle EE. Tobacco use and cancer: an epidemiologic perspective for genetics. Oncogene 21:7307-7325, 2002 3) Haussmann HJ. Smoking and lung cancer: future research directions. Int J Toxicol 26:353-364, 2007 4) Spiro SG, Silvestri GA. One hundred years of lung cancer. Am J Respir Crit Care Med 172:523-529, 2005 5) Pirozynsk M. 100 years of lung cancer. Respir Med 100: 2073-2084, 2006 6) Yasufuku K, Nakajima T, Motoori K, Sekine Y, Shibuya K, Hiroshima K, Fujisawa T. Comparison of endobronchial ultrasound, positron emission tomography and CT for lymph node staging of lung cancer. Chest 130:710-718, 2006 7) 통계청. 2005 년사망원인통계연보, 2006 8) Lam S, Kennedy TC, Unger M, Miller YE, Gelmont D, Rusch V, Gipe B, Howard D, LeRiche JC, Coldman A, Gazdar AF. Localization of bronchial intraepithelial neoplastic lesions by flurorescence bronchoscopy. Chest 113:696-702, 1998 9) Keityh RL, Miller YE, Gemmill RM, Drabkin HA, Dempsey EC, Kennedy TC, Prindiville S, Frankin WA. Angiogenic squamous dysplasia in bronchi of individuals at high risk for lung cancer. Clin Cancer Res 6:1616-1625, 2000 10) Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer Statistics 2001. CA Cancer J Clin 51:15-36, 2001 11) Leonhard M. New incoherent autofluorescence/fluorescence system for early detection of lung cancer. Diagn Ther Endos 5:71-75, 1999 12) Zellwegner M, Grosjean P, Goujon D, Monnier P, van den Bergh H, Wagnieres G. In vivo autofluorescence spectroscopy of human bronchial tissue to optimize the detection and imaging of early cancers. J Biomed Opt 6:41-51, 2001 13) Hung J, Lam S, LeRiche JC, Palcic B. Autofluorescence of normal and malignant bronchial tissue. Lasers Surg Med 11:99-105, 1991 14) Lam S, Hung J, Palcic B. Detection of lung cancer by ration - 404 -
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