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1 대한내과학회지 : 제 78 권제 3 호 2010 특집 (Special Review) - 췌장의낭종성질환 췌장의낭종성질환 - 수술혹은경과관찰 울산대학교의과대학내과학교실 방성조 김명환 Pancreatic cystic lesion-surgery or follow-up evaluation Sung-Jo Bang, M.D. and Myung-Hwan Kim, M.D. Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea The decision of surgical treatment for pancreatic cystic lesions may mainly depend on the malignant potential of each lesion. Surgical excision is the most optimal treatment for the mucinous cystic neoplasm due to its high malignant potential. On the other hand, intraductal papillary mucinous neoplasm (IPMN) is divided into main duct type and branch-duct type. Main duct IPMN has high risk of malignant transformation. Therefore, surgical resection has been recommended for all main duct IPMN. Branch duct IPMN has relatively low malignant potential, and usually shows slow progression. A branch duct IPMN that is asymptomatic, less than 3 cm in size and without mural nodules may be followed-up without resection. Serous cystic neoplasm is usually benign in nature. Surgical treatment for serous cystic neoplasm should be considered when definitive diagnosis being uncertain, larger than 4 cm in size, or presence of symptoms. Solid pseudopapillary neoplasm also has low malignant potential which needs surgical excision. Surgical treatment for pancreatic pseudocyst is considered in limited cases with complication, such as infection or bleeding, and which is not controlled with non-surgical treatment. Management strategy for pancreatic cystic lesions should be individualized, and the decision to resect or follow-up a lesion should be based on factors such as the presence or absence of symptoms, patient age, cyst size, grading of malignant potential, location of the lesion, and the surgical risk of the patient. (Korean J Med 78: , 2010) Key Words: Pancreas; Cystic lesion; Treatment 서론췌장의가성낭종이외의낭종성질환에대한수술적치료의필요성에대한판단은병변의악성화위험도가주된결정요인이된다 ( 표 1). 즉, 악성화위험도가높거나악성병변이의심되는경우에는우선적으로수술적치료를고려하게되고, 악성화위험도가낮은경우에는경과관찰을선택하게된다. 췌장의주요낭성종양중에서장액성낭성종양 (serous cystic neoplasm) 은악성화위험도가매우낮아경과관찰하는 것이원칙이며, 나머지점액성낭성종양은악성화위험도는어느수준이상으로서외과적절제가치료원칙이다. 낭성종양에서발생한악성병변의경우에는일반적으로췌장암이라고불리는췌장선암 (pancreatic ductal adenocarcinoma) 보다는진행속도도느리고수술적치료로완치가능성이높아서예후가좋은편이다. 실제임상에서는병변의악성화위험도와함께췌장수술의위험도, 환자의연령, 병변의위치등여러가지변수를함께고려하여치료방침을결정하여야한다 1,2)

2 - The Korean Journal of Medicine: Vol. 78, No. 3, Table 1. Clinical feature and grade of malignancy potential of five major cystic lesions of the pancreas SCN MCN IPMN SPN Pseudocyst Peak decade of life 7 th 5 th 6 th ~7 th 4 th variable Sex Female>male Female, mostly Male>female Female, mostly Male>female History of pancreatitis No No Not uncommon No Yes Location Evenly Body/tail Head Evenly Evenly Malignant potential Rare Moderate to high Main duct IPMN: high Branch duct IPMN: low Low None SCN, serous cystic neoplasm; MCN, mucinous cystic neoplasm; IPMN, intraductal papillary mucinous neoplasm; SPN, solid pseudopapillary neoplasm. 점액성낭성종양 (Mucinous cystic neoplasm) 점액성낭성종양은비교적악성화위험도가높은전암성병변으로간주되기때문에점액성낭성종양으로진단된경우에는수술에의한완전절제가원칙이다. 특히, 낭종내강내로유두상돌기모양의벽결절이관찰되면악성화로의진행을시사하는소견이므로수술적치료를서둘러야한다. 점액성낭성종양은결국에는낭선암으로진행하는것으로생각되며, 중년에발견된점액성낭성종양은수술로절제를하지않는다면대부분에서일생중악성화를경험하게된다. 악성변화가없는점액성낭성종양은수술로절제한경우예후가매우양호하여 5년생존율이 100% 에이르나, 악성화되어침습적점액성낭선암이되면수술로완전절제를하더라도예후는불량하여 5년생존율이 5~33% 에불과하다 3). 췌관내유두상점액성종양 (Intraductal papillary mucinous neoplasm, IPMN) 췌관내유두상점액성종양은주췌관형과분지형으로세분화되며, 혼합형도존재한다. 과거에는이종양이드물다고여겨졌으나 4) 이제는국내에서도흔하게발견되고있다. 췌관내유두상점액성종양은악성화위험이있으며, 아형에따라악성화위험정도가달라서치료방침에도차이가있다 5,6). 양성 IPMN 이나상피내암 (carcinoma in situ) 인경우에수술후 5년생존율은매우양호하여거의 100% 에가까우며, 수술시에임파선곽청술은필요하지않다 7). 그러나췌관내유두상점액성종양이침습적암으로진행한경우에 는일반적인췌장선암 (ductal adenocarcinoma) 에비하여임파선전이의빈도는낮으나 (22%), 수술로완전절제를시행한경우에도 5년생존율은 42~62% 로예후는불량한편이다 8). 1. 주췌관형췌관내유두상점액성종양 (Main duct IPMN) 주췌관형췌관내유두상점액성종양은악성위험도가높은전암성병변으로수술적치료가원칙이며, 수술시에는이환된병변부위의완전한절제가필요하다. 주췌관형은주췌관의현저한확장이특징적이며늘어난췌관내에고형성종괴가관찰되기도한다. 악성변화를시사하는임상소견으로는복통, 황달, 새로이발생한당뇨병등이있으나무증상인경우도적지않다 8). 임상에서흔히문제가되는것은환자가고령인경우가많아서수술적치료의필요성이수술적치료와관련된위험성보다명확히높은가하는것과수술을시행할경우에췌장전절제술을시행할것인가혹은부분췌장절제술을시행하여췌장의일부를남길것인가하는점이다. 췌장전절제술을시행하는경우에는병변의완전절제가가능하여완치율을높일수있다는장점이있으나, 수술과관련된이환율이높으며수술후췌장효소결핍에의한흡수장애, 2차성당뇨병등이필연적으로발생하므로삶의질적저하가문제이다. 부분췌장절제술을시행하는경우에는수술후삶의질저하의우려가덜하기는하나잔여병변이남거나남은췌장부위에서병변의재발우려가문제이다. 부분췌장절제술을시행하기위하여서는점액분비종양의존재부위를정확하게진단하여야한다. 일반적으로주췌관형췌관내유두상점액성종양은영상학적검사와내시경적검사에서여러가지특징적인소견들로인하여진단이크게어렵지는않으나, 점액분비종양이췌장의어느부위에존재하는가를정확하게진단하는것은매우어렵다. 점액의

3 - Sung-Jo Bang, et al. Pancreatic cystic lesion - Surgery or follow-up evaluation - 점성으로인하여병변의근위부와원위부모두에서췌관이미만성으로확장되므로확장된췌관의모양으로종양존재부위를정확하게추정하는것이불가능하다. 조직학적진단과병변의위치확인을위한경구적경로의췌관경검사가시도되기도하였으나 9,10), 특수한장비가필요하다는점과병변이다발성으로존재하는경우가있어병변이확인된부위를부분절제하였을때에도남은췌장부위에서의재발가능성을배제하기가어렵다는점등의제한점으로인하여널리시행되고있지는않다. 따라서병변의위치를명확히확인할수없는주췌관형 IPMN 에서는췌장전절제술이완전한병변의제거를위하여필요하겠으나, 개개의환자마다환자의연령, 전신상태, 수술위험도등을고려하여개별적으로치료방침을결정하여야한다 11). 2. 분지형췌관내유두상점액성종양 (Branch duct IPMN) 분지형췌관내유두상점액성종양은악성화위험도가있기는하나주췌관형보다는낮으며진행이느린것으로알려져있다 12). 분지형췌관내유두상점액성낭종의수술적응증으로는 3 cm 이상의크기, 벽결절의존재, 병변으로인한증상의발현등이있을경우에수술적치료를시행하는것이널리받아들여지고있으며 13,14), 이러한소견들은분지형 IPMN의악성변화예측에대한독립적위험인자들이다 15,16). 이러한소견이없을경우즉, 주췌관확장이없으면서낭종내부에벽결절이없고, 3 cm 이하크기인무증상의분지형 IPMN 에서는경과관찰할수있다. 이종양이나이든사람에게호발하고췌장두부에잘생기는것도경과관찰의한이유가된다. 경과관찰의방법과검사간격에대하여서는현재까지정립이되어있지않으나, 복부전산화단층촬영검사와자기공명영상담췌관조영검사 (magnetic resonance cholangiopancreatography, MRCP) 를 6개월마다번갈아검사를하자는의견과 17) 복부전산화단층촬영검사나복부초음파검사를 3, 6, 9개월간격으로시행하다가자기공명영상담췌관조영검사를매년시행하자는의견등이있다 11). 일부에서는내시경적초음파검사와낭종액분석도정기적으로시행할것을권유하기도한다. 그러나일부의장액성낭성종양은분지형췌관내유두상점액성종양과감별이어려운경우도있으며, 낭종의수가소수이고크기가큰경우에는점액성낭성종양과감별이어려운경우도있다. 따라서장액성낭성종양으로추정되는경우에서도악성화경향이있는병변과감별이어려울때는수술적치료가고려되기도한다 18). 현재까지전세계적으로장액성낭종의악성화증례는 25예가보고되어있으며 19), 저자에따라서는장액성낭종에서도증상이있거나경과관찰중크기가증가하는경우그리고 4 cm 이상크기의병변은수술적치료를권유하기도한다 20,21). 고형가성유두상종양 (Solid pseudopapillary neoplasm) 고형가성유두상종양은고형부위와낭성변화된부위가혼재하는특징이있으며, 젊은여성에서호발한다. 대부분에서양성종양인경우가많으나드물게간이나주위조직으로전이되는악성화의변화를보이는경우가있으며, 악성변화와관련된임상적양상이뚜렷하지않으므로고형가성유두상종양으로진단이되면수술적치료가권유된다 22). 일반적으로수술적치료에대한예후는양호한편이다. 췌장가성낭종 췌장의가성낭종은악성화위험이없다. 대부분의경우에서내과적치료로호전되므로경과관찰이우선적이다. 췌장의가성낭종에서수술적치료를고려하게되는경우는주로감염이나출혈등의합병증이발생한경우이다. 그러나이러한경우에서도내시경적위낭종배액술 (endoscopic cystogastrostomy), 내시경적괴사조직제거술등의치료적내시경술기의발전과각종배액관삽입및혈관을통한지혈시술등의중재적영상의학시술의발전으로인하여가성낭종의합병증에대한치료목적으로수술을시행하게되는경우는매우감소하였다. 명확히분류되지않는췌장의낭성병변 장액성낭성종양 (Serous cystic neoplasm) 장액성낭성종양은악성화위험도가매우낮으므로전형적인경우에서는수술적치료보다는경과관찰을권유한다. 해상도가높은여러영상학적검사의발전으로췌장의낭종성병변이우연히발견되는경우가점차로늘고있다. 췌장의낭성병변은위에서언급한종류외에도단순낭종, 내분비종양의낭성변성, 췌장암의낭성괴사, 낭성임파종등

4 - 대한내과학회지 : 제 78 권제 3 호통권제 595 호 Figure 1. Management strategy for cystic lesions of the pancreas. 1 Cyst <2 cm without septum and mural nodule. 2 Less than 3 cm in size and absence of mural nodule or symptom. 3 Symptomatic and/or larger than 3 cm in size and/or with mural nodule. 4 Based on age, location, and comorbidity. Sx, symptom; Hx, history; MCN, mucinous cystic neoplasm; SPN, solid pseudopapillary neoplasm; SCN, serous cystic neoplasm; Px, prognosis. 의다양한병변이있으며, 크기가작은경우에는각종영상학적검사나낭종액분석으로도감별진단이어려운경우가있다. 이러한경우에서는증상의유무, 병변의크기와위치, 환자연령등을고려하여수술적치료시행여부를결정하게된다. 최근복강경을이용한췌낭종절제술이활발히이용됨에따라 23) 낭성병변이췌장미부에있는경우에수술위험도가높지않은젊은환자에서는수술적치료를우선적으로고려하는경향이다 24). 췌장의낭성병변에대한비수술적치료로낭종내에탄올주입이나고주파를이용한제거등이시도되기도하였으나장기적인치료성적에대한연구결과가부족하여널리시행되고있지는않으며, 향후추가적인연구가필요하다 25). 2 cm 이하크기로서격벽이나벽결절이없는무증상낭종에서는수술보다는경과관찰이권유되며 26,27), 경과관찰의방법과간격에대하여서는명확히정립되어있지않다. 복부 초음파검사의경우에는인체에무해하다는장점이있으나췌장의체부와미부에대한관찰이어렵다는제한점이있다. 복부전산화단층촬영검사는췌장전체를세밀하게검사가가능하다는장점이있으나, 젊은환자에서장기간의추적관찰이필요한경우에는방사선노출의누적이부담된다. 복부자기공명영상검사의경우에는방사선노출에대한부담이없이췌장전체에대한자세한검사가가능하다는장점이있으나비싼비용이단점이다. 내시경초음파검사는낭종내벽결절의유무에대한검사예민도가가장우수하며췌장낭성병변의추적관찰에대한유용성이높이평가되고있다. 따라서복부초음파검사로병변이잘관찰되는경우에는복부초음파검사로경과관찰을할수있겠으나, 그렇지않은경우에는환자와병변에따라적절한검사종류와검사간격을결정하여야한다 ( 그림 1)

5 - 방성조외 1 인. 췌장의낭종성질환 - 수술혹은경과관찰 - 결 췌장의낭종성병변들중에서악성화위험도가있는전암성병변인점액성낭성종양과췌관내유두상점액성종양중주췌관형은수술적치료가원칙이며, 분지형췌관내유두상점액성종양은악성화위험이있기는하나비교적악성화위험도가낮고진행이느린것으로알려져있어크기가 3 cm 이상이거나벽결절이관찰되거나증상이발현된경우에수술적치료를고려한다. 고형가성유두상종양또한악성화위험도가있으므로수술적절제가원칙이다. 장액성낭성종양은악성화위험도가매우낮으므로전형적인경우에는경과를관찰하는것으로충분하다. 가성낭종의경우에는출혈, 감염, 통증등이비수술적치료로조절이되지않을경우에수술을고려하여야한다. 개개의환자에서수술적치료에대한결정은병변의악성화위험도외에도증상의유무, 환자의연령, 낭종의크기, 낭종의위치, 수술위험도등을함께고려하여야한다. 췌장의낭종성병변의경과관찰에대한검사종류와검사간격은정립되어있지않으나 6~12개월간격으로복부전산화단층촬영검사나복부자기공명영상검사시행이주로권유되며, 병변의크기와위치등과함께환자의연령, 전신상태, 수술위험성등을고려하여적절한검사종류와검사간격을결정하여야한다. 론 중심단어 : 췌장 ; 낭종성질환 ; 치료 REFERENCES 1) Oh HC, Kim MH, Hwang CY, Lee TY, Lee SS, Seo DW, Lee SK. Cystic lesions of the pancreas: Challenging issues in clinical practice. Am J Gastroenterol 103: , ) Brugge WR, Lauwers GY, Sahani D, Fernandez-del Castillo C, Warshaw AL. Cystic neoplasms of the pancreas. N Engl J Med 351: , ) Sarr MG, Carpenter HA, Prabhaker LP, Orchard TF, Hughes S, van Heerden JA, DiMagno EP. Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas: Can one reliably differentiate benign from malignant(or premalignant) neoplasm? Ann Surg 231: , ) Kim MH, Lee SK, Chung YH, Min YI, Han DJ, Lee MG, Yu ES. A case of mucinous ductal ectasia of the pancreas. Korean J Gastroenterol 24: , ) Sugiyama M, Atomi Y, Kuroda A. Two types of mucin-producing cystic tumors of the pancreas: Diagnosis and treatment. Surgery 122: , ) Kobari M, Egawa S, Shibuya K, Shimamura H, Sunamura M, Takeda K, Matsuno S, Furukawa T. Intraductal papillary mucinous tumors of the pancreas comprise 2 clinical subtypes: Differences in clinical characteristics and surgical management. Arch Surg 134: , ) Sugiyama M, Suzuki Y, Abe N, Mori T, Atomi Y. Management of intraductal papillary mucinous neoplasm of the pancreas. J Gastroenterol 43: , ) Salvia R, Fernández-del Castillo C, Bassi C, Thayer SP, Falconi M, Mantovani W, Pederzoli P, Warshaw AL. Main-duct intraductal papillary mucinous neoplasms of the pancreas: Clinical predictors of malignancy and long-term survival following resection. Ann Surg 239: , ) Seo DW, Kim MH, Lee SK, Yoo BM, Jung SA, Myung SJ, Min YI, Gong G, Auh YH. The value of pancreatoscopy in patients with mucinous ductal ectasia. Endoscopy 29: , ) Yasuda K, Sakata M, Ueda M, Uno K, Nakajima M. The use of pancreatoscopy in the diagnosis of intraductal papillary mucinous tumor lesions of the pancreas. Clin Gastroenterol Hepatol 3:S53-57, ) Tanaka M. Intraductal papillary mucinous neoplasm of the pancreas: Diagnosis and treatment. 28: , ) Terris B, Ponsot P, Paye F, Hammel P, Sauvanet A, Molas G, Bernades P, Belghiti J, Ruszniewski P, Fléjou JF. Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol 24: , ) Salvia R, Crippa S, Falconi M, Bassi C, Guarise A, Scarpa A, Pederzoli P. Branch-duct intraductal papillary mucinous neoplasms of the pancreas: to operate or not to operate? Gut 56: , ) Rodriguez JR, Salvia R, Crippa S, Warshaw AL, Bassi C, Falconi M, Thayer SP, Lauwers GY, Capelli P, Mino-Kenudson M, Razo O, McGrath D, Pederzoli P, Fernández-Del Castillo C. Branch-duct intraductal papillary mucinous neoplasms: Observations in 145 patients who underwent resection. Gastroenterology 133:72-79, ) Matsumoto T, Aramaki M, Yada K, Hirano S, Himeno Y, Shibata K, Kawano K, Kitano S. Optimal management of the branch duct type intraductal papillary mucinous neoplasms of the pancreas. J Clin Gastroenterol 36: , ) Sugiyama M, Izumisato Y, Abe N, Masaki T, Mori T, Atomi Y. Predictive factors for malignancy in intraductal papillary-mucinous tumours of the pancreas. Br J Surg 90: , ) Lévy P, Jouannaud V, O'Toole D, Couvelard A, Vullierme MP, Palazzo L, Aubert A, Ponsot P, Sauvanet A, Maire F, Hentic O, Hammel P, Ruszniewski P. Natural history of intraductal papillary mucinous tumors of the pancreas: Actuarial risk of

6 - The Korean Journal of Medicine: Vol. 78, No. 3, malignancy. Clin Gastroenterol Hepatol 4: , ) Hung JS, Yang CY, Hu RH, Lee PH, Tien YW. Surgical treatment of pancreatic serous cystadenoma: Aggressive for operations but limited resections. Pancreas 35: , ) King JC, Ng TT, White SC, Cortina G, Reber HA, Hines OJ. Pancreatic serous cystadenocarcinoma: A case report and review of the literature. J Gastrointest Surg 13: , ) Tseng JF, Warshaw AL, Sahani DV, Lauwers GY, Rattner DW, Fernandez-del Castillo C. Serous cystadenoma of the pancreas: Tumor growth rates and recommendations for treatment. Ann Surg 242: , ) Wargo JA, Fernandez-del-Castillo C, Warshaw AL. Management of pancreatic serous cystadenomas. Adv Surg 43:23-34, ) Yang F, Jin C, Long J, Yu XJ, Xu J, Di Y, Li J, Fu de L, Ni QX. Solid pseudopapillary tumor of the pancreas: a case series of 26 consecutive patients. Am J Surg 198: , ) Kim SC, Park KT, Hwang JW, Shin HC, Lee SS, Seo DW, Lee SK, Kim MH, Han DJ. Comparative analysis of clinical outcomes for laparoscopic distal pancreatic resection and open distal pancreatic resection at a single institution. Surg Endosc 22: , ) DiMagno EP. The pancreatic cyst incidentaloma: Management consensus. Clin Gastroenterol Hepatol 5: , ) Oh HC, Seo DW, Lee TY, Kim JY, Lee SS, Lee SK, Kim MH. New treatment for cystic tumors of the pancreas: EUS-guided ethanol lavage with paclitaxel injection. Gastrointest Endosc 67: , ) Handrich SJ, Hough DM, Fletcher JG, Sarr MG. The natural history of the incidentally discovered small simple pancreatic cyst: Long-term follow-up and clinical implications. Am J Roentgenol 184:20-23, ) Lahav M, Maor Y, Avidan B, Novis B, Bar-Meir S. Nonsurgical management of asymptomatic incidental pancreatic cysts. Clin Gastroenterol Hepatol 5: ,

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