호흡기질환에서의수술적진단방법 연세대학교의과대학흉부외과학교실영동세브란스병원백효채 Surgical Diagnostic Methods in Pulmonary Diseases Hyo Chae Paik, M.D. Department of Thoracic Cardiovascular Surgery, Yonsei University College of Medicine 비소세포폐암은전체폐암의약 80% 를차지하며 stage Ⅰ과 Ⅱ와같은초기폐암은발견이되면수술적치료로완치또는장기생존이가능하지만많은환자들은수술시기를지나서내원하기때문에주변조직이나장기의침범이동반함으로수술적치료만으로는장기생존이불가능하며방사선치료와항암요법의병행치료를필요로하는경우가많다. 폐암의조기진단을위해서는단순흉부 X-선촬영이나객담검사, low-dose CT등을정기적으로시행하는것이도움이될수도있으나경제적효율을고려하였을때어려운점이많다. 수술적치료이전에정확한진단및병기설정을필요로하는목적은수술적치료가도움이될수없는환자들을선별함으로서이병율과사망률이높은수술적치료를시행하는것을방지하는것에있다. 병기설정을위해서는먼저병변의위치와크기, 종격동림프절의전이유무, 주변조직으로의침범, 흉부외장기로의전이유무등을검사해야하고정확한임상적병기설정 (clinical staging) 을함으로서환자의생존기간을예측하고적절한치료방법을선택할수있다. 특히최근에많이시행하고있는 neoadjuvant therapy 는정확한 clinical staging 에근거를가지고시행해야하며가능한모든수단을동원하여정확한병기를설정하는것이중요하다. 방사선소견만으로 neoadjuvant 치료를시작하는것은수술만으로도완치가가능할수있는환자들에게부적합한치료를하는것이다. 따라서 Address for correspondence : Hyo Chae Paik, M.D. Department of Thoracic Cardiovascular Surgery, Yonsei University College of Medicine, Yongdong Severance Hospital, Kangnamku Dogokdong 146-92, Seoul, 135-720, Korea Phone : 02-3497-3380 Fax : 02-3461-8282 E-mail : hcpaik@yumc.yonsei.ac.kr Received : Jun. 15. 2004. Accepted : Jul. 15. 2004. 최근에는다양한비침습적조직검사와전신마취하에시행하는종격동경조직검사, 흉강경검사등을시행함으로서수술전에정확한병기를측정하여각각의병기에적합한치료를선택하는것이필요하다. Clinical staging은치료를시작하기이전에모든진단적방법을이용하여얻은결과이며 pathologic stag ing은수술후최종병리소견으로얻은결과이다. Cli nical staging의정확도에관해서는여러보고가있으며 pathologic staging 에비하여 24% 는 overstaged 되었고 20% 는 understaged 되었으며 1 cn0인환자들의 19% 는 pn1 이고 24% 는 pn2로보고되기도했다 2. 또 cn2로생각되었던환자들에서는 38% 가 pn0 또는 pn1 이었고 6% 는 pn3로결정이되어 3 clinical stag ing 만으로수술또는보조요법을이용한치료를하는것은바람직하지않다. 종격동림프절의검사방법으로는침습적방법 (Inva sive method) 과비침습적방법이있으며비칩습적방법에는 CT나 endoscopic ultrasound(eus) 와같이림프절의크기를가지고병기를결정하는방법과 PET와같이어떤물질의대사의정도를가지고결정하는방법이있다. 이와같은방법들은병기를예측할수는있겠으나조직진단을할수없는단점이있다. Chest CT는일반적으로림프절단면의크기가 1cm 이상되어야양성으로진단을하는데 4 1 cm 이하인경우도종격동경조직검사를하면 3-16% 가암세포침윤이발견되며림프절이커져있는경우에도수술시에확인한결과약 30% 는암세포침윤이없는것으로밝혀져단순히 CT 소견만으로수술결정을한다면모든환자의약 30% 는수술적치료가더좋은치료방법임에도불구하고약물또는방사선치료를먼저시행하는경우가있을수있고전원에게수술적치료를먼저시행한다면불완전한절제수술이될가능성이높은단점이있다. Miller등은 CT의 sensitivity는 71%, specificity는 11
HC Paik : Surgical diagnostic methods in pulmonary diseases Survival of Clinical vs Pathological Stage Clinical Stage Pathologic Stage pi ci cii ciiia, ciiib civ pii piiia Miller Ann Thorac Surg 1992;53:170 Cervical Mediastinoscopy 89% 로보고하였으며수술전에 N2와 N3 림프절의전이를측정하려면종격동경조직검사가전신마취하에시행해야하는단점이있음에도불구하고가장정확하게병기설정을할수있어가장좋은방법이라고하였다 5. 1. Standard cervical mediastinoscopy Standard cervical mediastinoscopy 의 sensitivity 는 72-89% 로보고되었으며 ( 표 1) 낮은이유는이방법으로는림프절 # 5,6,8,9에도달할수없기때문이다. 12
Tuberculosis and Respiratory Diseases Vol. 57. No. 1, Jul, 2004 Cervical Mediastinoscopy Blunt dissection paratracheally, bilaterally, and subcarinally paratracheal LN (2R,2L,4R,4L) pretracheal LN (1,3) anterior subcarinal LN (7) Node groups that cannot be sampled: posterior subcarinal (7) inferior mediastinal (8,9) APW and anterior mediastinal (5,6) Table 1. Sensitivity and specificity of cervical mediastinoscopy for staging of lung cancer. Author, year, ref No. of patients Sensitivity (%) Specificity (%) Funatsu, 1994, 28 Gdeedo, 1997, 29 Leschber, 2000, 30 Rami-Porta, 2002, 31 164 165 137 88 89 81 86 이병율및사망률은상당히낮으나종격동경검사를많이시행하지않는병원일수록합병증발생율은높으며 6 0예이상시행한병원에서의사망률은거의 0% 이고이병율은 0.5%-1% 로보고되었다 7. 일부병원에서는입원없이외래를통해서종격동검사를하는경우도있다 8. 종격동경검사의적응증으로는다음과같다. 1. Lung mass with bulky, unresectable mediastinal LN-a diagnosis and staging information 2. Enlarged but resectable LN-evidence of meta stases in multiple levels: a cohort with extre mely poor prognosis 3. T3 or T4 tumors regardless of LN size: no benefit of surgical resection in presence of LN metastasis 4. Synchronous bilateral pulmonary lesions-if me diastinal LN is negative, the tumors are treated as independent neoplasm (two early stage lung cancers) 5. Determine eligibility for neoadjuvant therapy trial 종격동경검사를시행하는원칙은각기관들마다차이가있다. 모든환자에서종격동경검사를하는것은논란이될수있으며종양의위치, 크기, 또는 CT상림프절비대유무에따라선택적으로종격동경을실시하는경우가많으며 CT상림프절비대가없는경우에는암세포의전이가없는것으로간주하고곧바로수술을진행하는경우도있다. 현재대부분의국제학회에서는치료하기전에시행한 chest CT 상림프절의단면이 1 cm 이하인경우에만종격동경검사를권장하고있다 9-11. 그러나 Hammoud 등 7 은모든환자에서종격동경검사를하는것을권장하였으며그이유로는폐암이의심되는 1745명에서검사를하여 76명 (8%) 에서만 N2 병변이있음에도불구하고찾아내지를못했으나이중 56명에서는종격동경으로도달할수없는부위 13
HC Paik : Surgical diagnostic methods in pulmonary diseases All negative Single positive Double positive Triple positive pn2, N3 pn0, N1 Total Statistic 2 (2.5) 11 (19.6) 16 (33.3) 19 (90.4) 76 (97.4) 45 (80.3) 32 (66.6) 2 (9.5) Totals 48 155 203 78 56 48 21 P<0.001 P<0.001 의 N2 병변이었으므로상당히좋은결과를얻었다고보고하였다. Kimura 등 12 은종격동경검사를시행하는기준을정하는데여러요인을추가하여종격동실시여부를결정하였다. 1. Tumor size > 2-3 cm 2. Lymph node > 1 cm on chest CT 3. Elevated tumor markers: CEA, CA19-9, CA- 125, NSE, Pro-GRP, AFP, CYFRA, SCC 위의 3가지인자를가지고 N2 병변을예측하고자하였으며 3가지요인이다음성인경우에 pn2와 pn3 병변이있을확률은 4% (2/48) 이며 pn2와 pn3환자의 96% (46 of 48) 에서는병변을예측할수있었고불필요한종격동경검사를 37% (76 of 203) 에서시행하지않았으며방사선검사로종격동림프절비대가없는경우에도 N2를발견할수있었다. 인자 3개가다양성일경우는 pn2,n3의확률이 90% 이상이었고반면에 3개의요인이다음성이면 pn2,n3의확률은 2.5% 밖에안되었다고보고하였다. Gupta 등은 13 종격동경검사를항시실시해야한다고주장하였으며시행하지않아도되는경우는다음과같은조건을충족시킬수있어야만되나아직은이를충족시킬수없으므로결과적으로는전체환자에서종격동경검사를시행하는것이바람직하다고하였다. followed by surgery for patients with N2 disease 좌상엽에발생한폐암은특별한주의가요구된다. 우측폐와좌하엽에발생하는폐암은종격동경으로도달할수있는림프절로전이가잘되는것에반하여좌상엽종양은종격동경으로관찰하기어려운 5번과 6 번림프절로전이가잘되기때문에 14 anterior medi astinoscopy, anterior mediastinotomy, extended cer vical mediastinoscopy 나 VATS를이용한림프절검사가요구된다. 그러나좌상엽병변이 5번이나 6번으로만전이가되어있는경우는 N1 환자들과비슷한예후를보인다는보고가있으며 15 만약이러한 minimal N2 병변도수술의적응증이안된다고생각하거나 neo-adjuvant therapy 가필요하다고한다면이들환자에서는필히 AP window 림프절의확인이필요하다 16. PET 검사가점차로많이활용되면서종격동경검사의필요성을조사하였다. Kernstine 등 17 은 237 명을대상으로 PET 시행후 31일이내에종격동경검사를시행하여 PET의 sensitivity, specificity, accuracy 는 82%, positive predictive value 는 51%, negative predictive value는 95% 로보고하였고 SUV<2.5 이하이면서 PET 상종격동이음성인경우에는조직검사결과와일치하여이런조건에만족하는경우에는 PET의 specificity 는 % 이므로일부선택된군에서는 PET이종격동경검사를대체할수도있을것으로보고하였다. -Sensitivity of non-invasive tests becomes % -Strategy of induction therapy becomes standard for all patients with operable/resectable stage IA, IB, IIA, IIB, and IIIA -Adjuvant therapy is shown to be equal to or better than that of induction therapy -Surgery alone is as good as induction therapy Complications of mediastinoscopy: Hemorrhage: bronchial arteries, major vessels, azygos vein Tracheobronchial tear Injuries of left recurrent laryngeal nerve and pleura Morbidity rate: 1.6%-2.3% 14
Tuberculosis and Respiratory Diseases Vol. 57. No. 1, Jul, 2004 Contraindications: Severe cervical arthritis preventing adequate extension Presence of a large cervical goiter Extensive calcification or aneurysmal dilatation of aortic arch or innominate artery Presence of tracheostomy 혹자는 standard cervical mediastinoscopy 외에추가로동측의 scalene lymph node를박리하는것을권하고있다. Lee and Ginsberg 는 18 non-squamous tumor 이면서 centrally located 된병변의경우는 scalene node의조직검사를함으로서약 15% 의환자에서예상하지못하였던 N3 node를발견하였다고하였으나 recurrent laryngeal nerve의손상가능성때문에조심해야한다고보고하였다. 앞으로 immunohi stochemistry 나 PCR 과같은 molecular methods 들이개발됨으로서림프절조직검사의 sensitivity는더욱향상될것으로기대된다. 2. Extended Cervical Mediastinoscopy: 이방법은 Ginsberg 등 19 이제안한방법으로서많이사용되지는않지만몇가지의장점이있다 20. -Extension of the standard cervical mediastino scopy -Through the suprasternal notch, directed lateral to the aortic arch -Alternative technique to avoid complications of mediastinotomy -Sensitivity of 83% -Diagnostic accuracy of 97% in examining APW and para-aortic LN -Subcarinal nodes are inaccessible 합병증으로는 cerebrovascular accident가있으며종격동경이 brachiocephalic 과 left carotid artery 근처에위치하게되는것과연관이있을것으로보이며 21 따라서 aortic arch에 calcification 이있는환자에서는시행하지않는것이좋다. 3. Anterior Mediastinotomy (Chamberlain Procedure): 이방법은 McNeill and Chamberlain 이 1966년에소개한방법으로 22 좌측의두번째또는세번째늑간을통하여 aortopulmonary window 의림프절을검사하는방법이다. 특히좌측폐의병변이있는환자에서유용하게쓰이며좌상엽에위치한종양의종격동침범유무를파악하는데도움이되며불필요한개흉술을약 30% 는줄일수있다고보고하였다 23. 우측에는 2R, 4R, 과 3번림프절의검사를할수있다. 이들림프 15
HC Paik : Surgical diagnostic methods in pulmonary diseases 완전히함몰시켜야만검사가가능하기때문에마취상문제를유발하는경우가있을수있고 VATS로는림프절 1번과좌측의 2번, 4번은검사가불가능하다는단점이있다. 합병증으로는수술후에장기간지속되는공기누출등이있다. VATS를이용하여체계적으로 N status를조사한보고는많지않으나 26,27 Roberts 등 26 은병변이하엽에위치하면서종격동경검사상음성인환자에서 8번과 9번림프절을검사하는데특히유용하다고보고하였다. 5. Intraoperative Mediastinal Nodal Staging 절은 Ginsberg 등이제안한 extended cervical media stinoscopy로도검사가가능하다. 4. Video-Assisted Thoracic Surgery(VATS): VATS는다양한목적으로사용이되고있으며특히수술전에반대측폐로의전이나늑막의 pleural seeding, malignant pleural effusion 등을발견하는목적으로자주사용되며늑막액세포검사상음성인경우에도약 60% 에서는 diffuse pleural dissemination을발견하였고 24 또수술전에 mediastinal infiltration 의정도를파악하는데에도유용하게쓰이며 stage IIIB 가의심되는환자의약 90% 에서정확하게진단이된다고보고되었다 24. 따라서모든환자에서개흉전에 VATS를권장하는의견도있으나예상외의 pleural seeding이발견되는경우는 2% 밖에는안되기때문에 25 대부분의병원에서는항상시행하지는않고있다. VATS는종격동경으로도달할수없는 5,6,8,9번림프절의조직검사를할수있기때문에종격동경검사상음성으로나왔으나 APW 나 subazygous nodes 등이커져있을때에도움이된다. 또흉벽의침범유무를아는데도큰도움이되며진단율은약 91% 이다. 그러나종격동을자세하게보기위해서는동측폐를 Accurate and thorough LN dissection is possible. Type of dissection -Sampling -Systematic sampling -Complete mediastinal node dissection Most aggressive LN dissection have no proven therapeutic value Some study-complete removal of all intrathoracic and supraclavicular LN in the drainage path way results in improved survival Conclusions 1. Mediastinoscopic biopsy is the most reliable sta ging method 2. VATS biopsy is effective in selected cases of left upper lobe and T4 lesions 3. Chest CT and PET in combination with the in vasive diagnostic method seems to be the most accurate means to avoid unnecessary thoracoto mies 4. The patient should never be denied potentially curative resection without tissue confirmation of malignant spread 16
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