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1 Korean J Gastroenterol Vol. 70 No. 1, pissn eissn REVIEW ARTICLE 외래에서우연히발견된췌장낭성종양에대한임상적접근 우용식, 이규택 1 한림대학교의과대학내과학교실, 성균관대학교의과대학내과학교실 1 Clinical Approach to Incidental Pancreatic Cystic Neoplasm in Outpatient Clinics Young Sik Woo and Kyu Taek Lee 1 Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul 1, Korea Cystic lesions of the pancreas are increasingly observed due to increased use of abdominal images. The malignant rate of pancreas cystic lesion varies widely between various types. Identification of malignant or high-risk lesions is important when determining the appropriate course of management. Using these image findings, including cyst size, presence of solid components, and pancreatic duct involvement, the 2012 International Association of Pancreatology (IAP) and the 2015 American Gastroenterological Association (AGA) guidelines provide a rationale in identifying higher risk patients requiring further workups using an endoscopic ultrasound (EUS). EUS with fine needle aspiration and cytology allows confirmation of the cyst type and determines the risk of malignancy. Small cysts with no suspicious features may undergo the regular imaging study for regular surveillance due to low risk for malignancy. In this review, the differences between the 2012 IAP and 2015 AGA guidelines are presented, In addition to possible recommendations for management and surveillance. (Korean J Gastroenterol 2017;70:13-20) Key Words: Pancreatic cyst; Pancreatic neoplasms; Endosonography; Endoscopic ultrasound-guided fine needle aspiration 서론 최근건강검진의보편화와복부초음파 (ultrasonography), 복부전산화단층촬영 (computed tomography, CT), 복부자기공명영상 (magnetic resonance imaging, MRI) 등점점더많은영상검사가임상에서사용됨에따라우연히발견되는췌장낭성병변이증가추세에있다. 1 영상검사에서발견된췌장낭종의유병률은 2-16% 이며, 고령에서증가하는것으로보고된다. 2-4 과거에는췌장낭성병변중대부분이가성낭종 (pseudocyst) 으로보고되었으나, 5 최근에는이들췌장낭성병변의상당수는낭성종양으로보고되고있다. 또한수술받은환자를대상으로한연구에서전암성및악성병변의빈도 는 30-47% 로보고되었다. 6,7 일반적으로췌장낭성종양은 CT 혹은 MRI에서확인되는영상학적특징으로최초진단된다. 내시경초음파 (endoscopic ultrasonography, EUS) 는높은해상도로추가적인영상학적정보를제공할수있고, EUS 유도하미세바늘흡인술 (endoscopic ultrasound guided fine needle aspiration, EUS-FNA) 로얻은낭액의분석은췌장낭종의감별진단에도움을줄수있다. 이러한진단을바탕으로수술적절제술이나추적관찰을결정하게된다. 하지만실제임상에서는병변의악성화위험도와췌장수술의위험도, 환자의연령, 병변의위치등여러가지변수를함께고려하게된다. 최근췌장낭성종양의자연경과나예후인자등에대한지식이늘어나면서치료방안은지속적으로발전하고있다. Received June 8, Revised June 26, Accepted June 27, CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright Korean Society of Gastroenterology. 교신저자 : 이규택, 06351, 서울시강남구일원로 81, 성균관대학교의과대학삼성서울병원소화기내과 Correspondence to: Kyu Taek Lee, Division of Gastroenterology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. Tel: , Fax: , ktcool.lee@gmail.com Financial support: None. Conflict of interest: None. Korean J Gastroenterol, Vol. 70 No. 1, July

2 14 우용식, 이규택. 우연히발견된췌장낭성종양 2006년췌장낭성병변의치료방침으로 International Sendai Consensus Guideline이발표되었고, 8 그이후여러개정사항들이제안되고있다. 9,10 본고에서는최근발표된진료지침들을중심으로우연하게발견된췌장낭종의진단적접근과치료방법즉, 경과관찰, 수술적치료에대하여고찰해보고자한다. 본론 1. 췌장낭성종양의분류췌장낭종은종류에따라서다양한악성위험도가있는것으로알려져있다 (Table 1). 점액성낭성종양 (mucinous cystic neoplasm, MCN) 과췌관내유두상점액성종양 (intraductal papillary mucinous neoplasm, IPMN) 같은점액성종양은악성화가능성이있는전암성병변으로생각한다. 고형가유두상종양 (solid pseudopapillary neoplasm, SPN) 의경우위험도는낮으나전암성병변으로간주하고있다. 이에반해장액성낭성종양 (serous cystic neoplasm, SCN) 은악성화가능성이거의없어양성종양으로판단한다. 그외에도내분비종양 (endocrine tumor) 이나관상선암 (ductal adenocarcinoma) 에서내부괴사로인한낭성변화를동반한고형종양도영상학적인넓은의미의낭종이라볼수있다. 실제발생률은정확하게알려져있지않으나수술로확진된환자를대상으로한국내연구의결과 IPMN이 40% 로가장높았고, MCN 25%, SCN 18%, SPN이 15% 였다. 11 수술로확진된환자를대상으로한외국연구에서추정상대발생률은 IPMN이 51%, MCN 이 11-18%, SCN이 13-23%, SPN이 2-5% 순이었다. 12 IPMN은유두상으로성장하는점액성췌관세포에의해점액이다량생산되어췌관이확장하게되는질환이며, 전암성병변으로인식된다. 환자는무증상일수도있고, 15% 의 IPMN 환자에서확장된췌관소견이보이며, 점액분비로인하여췌관이막혀폐쇄성췌장염이발생할수있다. 13 IPMN은췌관에서발생하는종양으로발생부위에따라서주췌관형 (main duct type, 다른폐색의원인을배제할수있으면서주췌관직경이 5 mm 이상분절형혹은미만형으로확장된경우 ), 분지췌관형 (branch duct type, 주췌관의확장없이췌관과교통이되는분지췌관에서발생하는경우 ), 혼합형 (mixed type, 주췌관및분지췌관형모두를만족하는경우 ) 으로분류된다. 9 주췌관형 IPMN (main duct-intraductal papillary mucinous neoplasm, MD-IPMN) 은대부분악성으로진행된다고알려져있고, 분지췌관형 IPMN (branch duct-intraductal papillary mucinous neoplasm, BD-IPMN) 은그중일부만이악성으로이행된다고알려져있다. MD-IPMN의악성화가능성은 38-68% 로보고되고있고, 9,14-16 혼합형 IPMN (mixed type- intraductal papillary mucinous neoplasm, mixed-ipmn) 에서도비슷한수준으로알려져있다. BD-IPMN의경우 12-47% 로악성화가능성이보고되어있으나, 대부분의연구가수술받은환자를대상으로이루어져실제악성화빈도는낮을것으로생각된다. MCN은주췌관과의교통은없으며낭내부는점도가높은액체로채워져있는것이특징이다. 주로중년의여성에서호발하고, 췌장의체부및미부에서발생한다. 21 MCN의가장큰조직학적특징은난소간질 (ovarian stroma) 이라고불리는상피바로아래에세포밀도가높은간질층 (stromal layer) 이있다는것이며, 이것이 IPMN과의차이점이다. 22 MCN의악성화빈도는 10-17% 로보고되고있고, 23,24 선종에서부터침습성선암종까지다양한악성도를보이나대다수의환자에서악성종양으로진행할수있어수술적절제가원칙이다. SPN은처음에는고형종양으로시작되나병변이커지면서병변내부가괴사하고, 낭성변화된부위가혼재되는특징이있다. 발생빈도는매우낮으며, 주로 Table 1. Chracteristics of Pancreatic Cystic Lesions Type of cyst Key features Malignancy rate, % Intraductal papillary mucinous neoplasm Main duct Mucinous. Segmental or diffuse dilatation of MPD. MPD diameter >10 mm is highly suggestive of malignancy and 5-9 mm is moderately suggestive of malignancy ,14-16 Branch duct Mucinous. Communicates with MPD and no MPD dilatation Mixed Satisfy criteria for both main duct and branch duct IPMN ,14-16 Mucinous cystic neoplasm Mucinous. No communication with duct ,24 Occurs exclusively in middle age female (mean age, y). Body and tail of pancreas most common locations. Solid pseudopapillary neoplasm Rare. Occurs more often in young female (mean age, 30 y) Large, mixed solid and cystic lesion. Serous cystic adenoma Serous. Honeycomb appearance and central scar. Macrocystic variant appears similar to MCN. 0 MPD, main pancreatic duct; IPMN, intraductal papillary mucinous neoplasms; MCN, mucinous cystic neoplasm. The Korean Journal of Gastroenterology

3 Woo YS and Lee KT. Incidental Pancreatic Cystic Neoplasm 대젊은여성의영상학적검사에서고형또는낭성으로나타날수있고, 경계가명확하며중심부에석회화가동반되는특징을보인다 % 에서주변침범이나전이가가능하 여 수술적절제가권고된다. SCN 은악성화의가능성이 매우낮아증상이있는경우를제외하고수술적절제술은권고되지않는다. Microcystic SCN의경우영상검사에서벌집모양의소낭으로나타나고, 중심반흔및특징적인모양의석회화소견이관찰된다. 29,30 2 cm 이상크기의 macrocystic SCN의경우때때로다른점액성낭종과감별이어려울수있다 우연히발견된췌장낭성종양에대한임상적접근과치료방침 : 권고사항중심으로통증을동반한췌장낭종의경우전암성혹은악성화병변의가능성이높다. 6 임상적특징과악성화유무의연관성을분석한연구에서도증상의유무가독립적인위험인자로보고되고있다. MD-IPMN과 mixed-ipmn에서 BD-IPMN보다증상을보이는경우가더많고, 악성화비율도높다. IPMN 종류와관련없이증상발생기간이길어질수록악성화발생가능성이증가하는것으로알려져있다. 32,33 따라서증상을가진췌장낭종환자에서수술적치료를적극적으로고려해야한다. 복부 CT 혹은 MRI 영상검사소견중악성화와관련된특징이알려져있다. 주췌관직경 10 mm 이상과조영증강되는고형병변과같은영상학적특징은췌장낭종의악성화고위험인자로알려져있다. 다른위험인자로는낭종의크기가 3 cm 이상, 낭종벽이두꺼워지거나조영증강되는경우, 조영증강되지않는벽결절 (mural nodule), 주췌관직경이 5-9 mm, 주췌관직경의갑작스러운변화및원위부췌장위축, 림프절종대가있다. 10 mm 이상주췌관확장소견은고위험 MD- IPMN, mixed-ipmn에서특징적인소견으로, 많은연구에서악성화예측의독립적인인자로확인되었다. 15, mm 주췌관확장소견은적은비율이지만악성화와관련있는것으로보고되었다. 16,34,35 낭종내고형종괴 (solid component) 혹은벽결절의존재는낭종의크기나종류와관련없이 MCN, IPMN 모두에서악성화와높은관련성을보인다. 18,34,36 또한낭종의크기가크거나추적관찰중크기가증가하는경우 벽결절이동반될가능성이있다. 37,38 낭종크기를수술적치료의단독지표로사용하는데논란이있는데, BD-IPMN에서직경 30 mm 이상의낭종은악성과의연관성이그리높지않은것으로보고되고있고, 39 직경 30 mm 이하의부췌관형 IPMN에서도침윤성암이발견되었다는보고가있으므로낭종의크기가절대적인악성화의예측인자는아니다. 40 직경이 3 cm 이상인낭종에대하여수술적치료를권고한 2006 International Association of Pancreatology (IAP) 와다르게 2012 IAP에서는걱정스러운특징 (worrisome features, WFs) 이없는 3 cm 이상의병변은내시경초음파를시행하여벽결절이나낭종벽의두께증가가없으면특히고령에서는수술적치료보다는관찰을권고하였다. 최초영상검사결과를바탕으로다음과같은경우에는추가검사없이추적관찰이가능하다. Microcystic SCN을시사하는벌집모양과중심반흔의소견이관찰되는낭종의경우악성화가능성이거의없기때문에증상이없는경우추적관찰이가능하다. Macrocystic SCN의경우영상검사자체만으로 MCN과구분이불가능하기때문에 EUS를시행하여낭종의모양을관찰하거나낭종천자액의 carcinoembryonic antigen (CEA) 을확인하는것이필요하다. 위험인자가없는무증상낭종을가진 1,735명을대상으로 23.5개월동안추적관찰을시행한연구에서 1 cm 미만 0.3%, 1-2 cm 0.6%, 2-3 cm 1.3% 에서낮은악성화빈도를보고하였다. 41 CT와 MRI의발전에도불구하고췌장낭성병변, 특히크기가작은경우감별진단에는제한점이있으며, EUS의역할이중요하다. EUS는내부구조를관찰하는것이유리하여악성낭종을진단하거나고위험낭종을확인하는데도움을줄수있다. EUS는단독으로낭종크기를확인하는데 CT와대등하고, 벽결절을확인하는데뛰어나다. 42,43 수술을시행한 154명의췌장낭성병변에대한 EUS의민감도는 76% 로, CT 와 MRI보다민감도에서각각 48%, 34% 더우수하다고보고하였다. 하지만시술자간차이점이있고, 수술을시행한환자만포함되어표본의편중 (selection bias) 이있다는문제점이있다. EUS-FNA 시행이 CT와 MRI에비해서각각 36%, 54% 진단정확도의상승을보이고, 감별이어려운낭종의경우는객 Table 2. Cystic Fluid Analysis for Incidental Pancreatic Cystic Lesion Diagnostic performance Positive result String sign (>1 cm, >1 sec) 95% specificity 44 Mucinous CEA >192 ng/ml 73% sensitivity, 84% specificity 45 Mucinous CEA <5 ng/ml 100% sensitivity, 86% specificity 46,47 Serous Amylase <250 U/L 44% sensitivity, 98% specificity 48 Exclude pseudocyst Cytology Poor sensitivity, high specificity Malignant CEA, carcinoembryonic antigen. Vol. 70 No. 1, July 2017

4 16 우용식, 이규택. 우연히발견된췌장낭성종양 관성과정확도를높이기위해서 EUS-FNA를시행하여낭종액과분석함으로써진단에도움이된다. 낭액천자로낭액의점도검사, 생화학적분석, 종양표지자검사, 세포검사등으로감별을시도할수있다 (Table 2). 낭액의점도를판단할수있는 string sign ( 천자침끝에서 1 cm, 1초이상점도유지 ) 양성인경우 MCN이나 IPMN으로진단하는데, 95% 특이도를보인다. 44 췌장낭성병변에서의낭액의종양표지자중 CEA가가장민감도가높은표지자로알려져있고, 점액성낭종과비점액성낭종을감별하는데도움을준다. CEA는 192 ng/ml 이상일때점액성종양진단의민감도는 73%, 특이도 84% 로보고되었다. 45 CEA가 5 ng/ml 이하일때 SCN, 가성낭종진단의민감도는 100%, 특이도 86% 로보고하였다. 46,47 낭액의아밀라제수치가많이높은경우는가성낭종을강하게의심할수있으나, 250 U/L 이하인경우가성낭종은배제할수있다. 48 췌장낭종의천자액세포검사의가장큰단점은췌장낭종액에는세포수가적어서진단이어렵고민감도가낮다는점이지만, 악성변화가있을때에민감도가올라가고특이도는매우높다. 우연하게발견된췌장낭종병변을임상적으로접근할때 (1) 낭종의종류, 점액성혹은비점액성낭종, (2) 현재악성화소견의유무, (3) 악성화진행가능성의유무를고려하는것이중요하다. 현재까지췌장의낭성종양의전향적연구가부족한상태로, 췌장낭성종양의자연경과와예후에대한정보는제한적이다. 또한수술적절제후에종양성병변의감별과악성화유무는정확한진단이가능하기때문에, 수술을하지않은상태에서영상학적정보를바탕으 로악성화에대한위험도분류및적절한추적관찰은실제임상에서매우어려운과제이다. 2006년에 IPMN과 MCN에대한국제적합의진료지침 (international consensus guidelines, IAP) 이발표된이후, 최근여러진료지침들이발표되었다. 2012년에국제췌장학회개정판 (2012 IAP) 이발표되어현재까지많이이용되고있다. 8,9 또한, 최근 2015년에는미국소화기학회 (American Gastroenterology Association, 2015 AGA) 에서무증상췌장낭성종양에국한하여새로운진료지침을발표하였다 IAP에서는 IPMN과 MCN에대한진료지침으로복부 CT 또는 MRI의영상소견을바탕으로고위험인자 (high-risk stigmatas) 와 WFs로분류하였다 AGA 가이드라인은우연하게발견된무증상췌장낭종에대한진료지침으로세가지고위험인자 (high-risk features, HRF) 를제시하였다 (Table 3) IAP에서폐쇄성황달, 주췌관직경 10 mm 이상 ( 주췌관형이나혼합형 ) 과조영증강되는고형병변을고위험인자 (high-risk stigmatas) 로정의하였고, 수술적절제를권고하였다. WFs ( 췌장염, 낭종직경 3 cm, 조영증강되는낭종벽이두꺼워진경우, 조영증강이되지않는벽결절, 주췌관직경 5-9 mm, 췌장실질의위축을동반한주췌관직경의갑작스런변화 ) 중하나이상을가진환자에서 EUS를실시하여 EUS에서벽결절이관찰되거나주췌관침범소견, 세포검사에서양성인경우수술적절제를권고하였다. 낭종의크기가 3 cm 이상인젊은환자의경우, 위험인자를보이지않는경우에도수술을적극적으로고려하도록권고하였다 AGA Table 3. Difference between the 2012 IAP and the 2015 AGA Guidelines for the Management of Pancreatic Cysts 9, IAP 2015 AGA Targeted patients Suspected MCN and IPMN All incidental pancreatic cysts Recommended image modality Pancreatic protocol CT or MRI Pancreas MRI with MRCP Risk factor High-risk stigmatas Obstructive jaundice Enhancing solid component MPD 10 mm Worrisome features High-risk features Cyst >3 cm Cyst >3 cm Thickened/enhancing cyst wall Associated solid component MPD 5-9 mm Dilatated MPD Nonenhancing mural nodule Abrupt change in PD caliber with distal pancreatic atrophy Threshold for EUS 1 worrisome feature At least 2 risk factors Threshold for surgery 1 high-risk stigmata Surveillance protocols in unresected cyst Frequent surveillance based on cyst size MRI in 1 yr and then every 2 yr Stopping surveillance in unresected cyst No recommendation to stop After 5 yr of stable cyst Surgically unfit patients IAP, International Association of Pancreatology; AGA, American Gastroenterological Association; EUS, endoscopic ultrasonography; MCN, mucinous cystic neoplasm; IPMN, intraductal papillary mucinous neoplasm; CT, computed tomography; MRI, magnetic resonance imaging; MPD, main pancreatic duct; PD, pancreatic duct; MRCP, magnetic resonance cholangiopancreatography. The Korean Journal of Gastroenterology

5 Woo YS and Lee KT. Incidental Pancreatic Cystic Neoplasm 17 가이드라인에서는우연히발견된췌장낭종의 HRF ( 낭종직경 3 cm, 고형성분, 주췌관확장 ) 를제시하였다. 2개이상의 HRF가발견되었거나추적관찰중의미있는변화가있는경우 EUS-FNA를실시하도록권고하고있다. 각각의진료지침에서 EUS-FNA 권고기준의차이를보이지만단일위험요인을가지는경우에도악성화가능성이있으므로적극적으로 EUS-FNA를고려하는것이필요하다 (Table 4). EUS에서고형성분과주췌관확장소견이둘다있는경우혹은악성화소견을시사하는세포가확인되는경우에수술을권고하고있다 (Table 5). 내시경초음파유도하췌장낭종절제술 (endoscopic ultrasound guided pancreatic cyst ablation, EUS-PCA) 은기저질환이나다른이유로수술대상이되지못하는경우차선책의치료방법으로소개되었다. 49 일반적으로 EUS 유도하에 22 G의세침으로병변을천자후낭액을흡인하여성상을확인하고, 흡인한낭액의양만큼의 % 에탄올의주입과흡인을반복하거나주입하여 3분경과한뒤제거한다. 세침을제거하기전 paclitaxel 또는 gemcitabine과같은항암제를주입할수있다. 50,51 EUS-PCA 시술후 CT를통하여추적관찰하여반응여부를판단하게되고, 현재까지보고에따르면 33-79% 까지완전소실 (complete resolution) 을보였다. 시술 Table 4. Recommended Indication for Endoscopic Ultrasound Guided Fine Needle Aspiration of Pancreatic Cysts Cyst size 3 cm Diameter of main pancreatic duct >5 mm Solid component Thickened or enhanced cyst wall Change of cyst size during surveillance 과관련된합병증은약 8-9% 에서발생하였고, 발열, 췌장염, 낭종내출혈, 낭종주변으로유출, 비정맥폐색, 간문맥혈전증등이보고되어비교적안전한시술로판단된다. 49,52,53 EUS-PCA 의적응증은아직정립되어있지않으나일반적으로다음과같은경우고려할수있다. 첫째로 2-4 cm 크기의 unilocular 또는 oligolocular 형태로췌관교통이없고악성화증거를보이지않는낭종, 둘째로추적기간동안크기가증가한낭종, 셋째로수술을거부하거나수술고위험환자들의낭종이대상이다. 54,55 낭성종양이서서히자라고악성으로진행하는데 5-10년이상의시간이걸리고, EUS-PCA를시행한후치료효과에대한병리학적확인이어렵기때문에시술에대한적응이되는대상을선정하는것과치료효과에대한논란이있다. 최근연구에서완전관해를보인환자중 6년추적관찰에서 98.3% 에서관해유지가보고되어 53 향후췌장낭종의치료방법으로임상적유용성이기대된다. 영상검사에서악성을시사하는위험인자가없는저위험도췌장낭종의경우추적관찰이가능하다. 낭종의크기가 3 cm 이하, 주췌관확장이없는경우, 고형성분이관찰되지않는경우는악성위험도가낮으므로수술치료하지않고추적관찰이필요하다. 추적관찰을위한영상검사에는 EUS, CT, MRI가이용되고있다. MRI의경우 CT보다낭종의췌관과의교통, 결절의해상도가우수하고, 방사선피폭을피할수있는장점이있다. Gadolium을사용하지않은 non-contrast MRI 에서도악성화를감별하는데비슷한효과를보인다는보고가있다. 56 EUS도방사선피폭이없고, 좋은해상도를가졌다는장점이있지만시술자간소견의차이를보일수있다는단점이있다 IAP 가이드라인에서는크기에따라관찰간격을제시 Table 5. Recommended Indications for Resection of Pancreatic Cysts in Accordance to the 2012 IAP and the 2015 AGA Guidelines 9,10 Diagnosis 2012 IAP 2015 AGA MCN Resection Resection MD-IPMN Resection Resection a Mixed-IPMN Resection Resection a BD-IPMN Pancreatitis (for relief of symptoms) Obstructive jaundice Solid component MPD >10 mm Cytologic features of adenocarcinoma Definite mural nodule on EUS MPD features suspicious for involvement c >3 cm cyst in young surgically fit patient Solid component and MPD >5 mm (both on EUS and MRI) and/or concerning features on EUS and EUS-FNA b IAP, International Association of Pancreatology; AGA, American Gastroenterological Association; MCN, mucinous cystic neoplasm; MD-IPMN, main duct intraductal papillary mucinous neoplasm; Mixed-IPMN, mixed type-intraductal papillary mucinous neoplasm; BD-IPMN, branch duct intraductal papillary mucinous neoplasm; MPD, main pancreatic duct; EUS, endoscopic ultrasonography; MRI, magnetic resonance imaging; EUS-FNA, endoscopic ultrasound guided fine needle aspiration. a Presence of a nodule or malignant cytologic features; b Definite mural nodule, positive cytology for malignancy; c Presence of thickened walls, intraductal mucin, or mural nodules is suggestive of MPD involvement; in their absence, MPD involvement is inconclusive. Vol. 70 No. 1, July 2017

6 18 우용식, 이규택. 우연히발견된췌장낭성종양 하고있다. 2-3 cm인경우 MRI와 EUS를번갈아가면서 3-6 개월마다추적검사할것을권고하고있다. 또한낭종의크기가 1-2 cm이면 CT나 MRI로해마다추적검사를하고변화가없으면검사간격을늘리고, 1 cm 미만이면 2-3년마다추적검사할것을권고하고있다. 9 AGA 가이드라인은단순하게 1년후 MRI를시행하고, 이후 2년마다 MRI 시행을권고하고있다. 5년동안추적관찰을하였지만의미있는변화가관찰되지않는경우, 추적관찰을종료할것을권고하고있다. 또한수술적치료의위험성이더높아서수술적치료대상이되지않는경우에는추적관찰을권고하지않았다. 10 하지만이를뒷받침할수있는췌장낭성종양의자연경과에대한연구는부족한실정이다. 최근후향적연구로 310명의환자를대상으로 5년이상악성화유무를확인하였는데, 이중 1% 인 3명의환자에서만침윤성암종이발견되었고, 고위험인자가없는환자에서는침윤성암종이발생하지않았다는보고가있다. 57 의료수가가비싸고비용대비효율성을중시하는미국의경우이 1% 의의미를 5년이후에는추적검사가불필요하다는쪽으로해석하지만, 췌장암의치명성과위험성을강조하는나라에서는이때문에 5년이후에도지속적으로추적검사가필요하다고해석할수있다. 추적검사의중단시기를결정하는것에있어서또하나의고려사항은기대여명이다. 20년이상의기대여명이예상되는젊은나이의환자에서는중단시기에관한진료지침을그대로적용하는것보다는지속적으로추적관찰을하는것이이득이될수도있을것이다. 실제임상에서는각각의환자의특성과상황에맞는추적관찰방법과중단시기를선택해야하겠다. 이러한진료지침의정확도는명확하게알려져있지않으나수술전영상을바탕으로낭종을분석하고수술후병리학적결과를비교한평가한연구들이있다. 수술을받은 317명의낭종환자의결과를 2012 IAP 진료지침에따라서분류하였고, 양성예측도와음성예측도는각각 88%, 92.5% 였다. 비록고이형성증이나침습암소견을가지지않는일부낭종환자가불필요한수술을시행받았지만, 2006 IAP 진료지침과비교하여상대적으로더많은환자가불필요한수술을피할수있었다. 35 두진료지침은 IPMN의수술기준에서차이를보이는데, 2012 IAP와다르게 AGA 진료지침에서는악성세포검사소견이나벽결절없이주췌관확장만있는경우수술을권고하지않는좀더보수적인입장을보였다. AGA 유효성을분석한연구에서고이형성증낭종이나악성낭종을가진환자가누락되었다는연구결과들이있었다. 58,59 최근 115명의수술적치료를받은환자에서두가지진료지침을비교하였고, AGA 진료지침에서는전암성낭종, 악성낭종을가진환자중 11% 가누락되었다. 이에반해 IAP 진료지침기준에서는누락된전암성낭종, 악성낭종을가진환자가없었다. 60 결 론 최근우연히발견된췌장낭성병변은지속적으로증가하고있고, 비종양성병변에서악성종양까지병리적으로다양한질환을구성하고있다. 악성화위험이있는점액성종양 (MCN, MD-IPMN) 과증상이있는낭성종양은수술이원칙이다. 최근진료지침에서악성화위험도예측가능한영상의학소견을제시하였다. 낭종내벽결절, 10 mm 이상의주췌관의확장, 세포검사에서비전형적세포는수술적절제가필요한고위험인자이다. 3 cm 이상의낭종크기, 5 mm 이상의주췌관의확장, 낭종벽이두꺼워지거나조영증강되는경우는내시경초음파시행이필요한위험인자이다. 췌장낭종에대한진료지침들이존재하지만각각장단점을보이고있다. 또한수술에대한위험성이상존하므로개개의환자에서치료와추적관찰에대한결정은병변악성화위험도, 환자의연령, 낭종의위치, 수술위험도등을함께고려하여야한다. REFERENCES 1. Edirimanne S, Connor SJ. Incidental pancreatic cystic lesions. World J Surg 2008;32: de Jong K, Nio CY, Hermans JJ, et al. High prevalence of pancreatic cysts detected by screening magnetic resonance imaging examinations. Clin Gastroenterol Hepatol 2010;8: de Jong K, Bruno MJ, Fockens P. Epidemiology, diagnosis, and management of cystic lesions of the pancreas. Gastroenterol Res Pract 2012;2012: Chang YR, Park JK, Jang JY, Kwon W, Yoon JH, Kim SW. Incidental pancreatic cystic neoplasms in an asymptomatic healthy population of 21,745 individuals: large-scale, single-center cohort study. Medicine (Baltimore) 2016;95:e Balthazar EJ, Chako AC. Computed tomography of pancreatic masses. Am J Gastroenterol 1990;85: Fernández-del Castillo C, Targarona J, Thayer SP, Rattner DW, Brugge WR, Warshaw AL. Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients. Arch Surg 2003;138: ; discussion Goh BK, Tan YM, Cheow PC, et al. Cystic lesions of the pancreas: an appraisal of an aggressive resectional policy adopted at a single institution during 15 years. Am J Surg 2006;192: Tanaka M, Chari S, Adsay V, et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology 2006;6: Tanaka M, Fernández-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 2012;12: Vege SS, Ziring B, Jain R, Moayyedi P; Clinical Guidelines Committee; American Gastroenterology Association. American gastroenterological association institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic The Korean Journal of Gastroenterology

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