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1 Korean Journal of HBP Surgery Vol. 13, No 2, June 원저 단일기관에서경험한신세포암의췌장전이치료경험 Renal Carcinoma Cell Metastasis into Pancreas : A Single Center Experience Introduction: Renal cell carcinoma (RCC) is a relative rare tumor, accounting for approximately 3% of adult malignancies. Renal cell carcinoma has a high metastatic potential and is renowned for its ability to spread to almost any organ of the body. Pancreas is a rare site for metastasis from other primary cancers. Moreover, pancreatic metastasis is difficult to differentiate and may be misdiagnosed as a primary pancreatic cancer. The aim of this study was to review our cases of renal cell carcinoma that had metastasized to the pancreas after radical nephrectomy. Methods: We did a retrospective review of the records of 4 patients with pathologically confirmed RCC that had metastasized to the pancreas after radical nephrectomy. Results: Our group of 4 patients consisted of 2 men and 2 women. Their average age was 58.7 years (± years). The locations within the pancreas were the head, in 2 (50.0%) and the body/tail in 2 (50.0%) patients. The pancreatic metastases were treated by pancreaticoduodenectomy in 2 patients, and by distal pancreatectomy in 2 patients. Median survival duration was (± 67.3 months) "Median" is associated with an interquartile range (25% to 75%). The number 67.3 appears to be a standard deviation which is associated with the "mean". Conclusions: RCC is an unpredictable tumor that may result in a late metastasis even from an early stage. Aggressive surgical management of pancreatic lesions offers a chance of long-term survival. 차장호, 박준성, 황호경, 김재근, 윤동섭, 이우정, 지훈상 연세대학교의과대학외과학교실 Jang Ho Cha M.D., Joon Seong Park, M.D., Ho Kyung Hwang, M.D., Jae Keun Kim, M.D., Dong Sup Yoon, M.D., Woo Jung Lee, M.D., Hoon Sang Chi, M.D. Department of Surgery, Yonsei University College of Medicine, Seoul, Korea. 책임저자 윤동섭주소 : 서울시강남구도곡동 우 강남세브란스병원외과학교실 Tel : Fax : yds6110@yuhs.ac 본논문의요지는 2009 년 4 월한국간담췌외과학회춘계학술대회에서포스터되었음 Key Words : Renal cell carcinoma, Pancreas, Metastasis, Pancreatectomy 중심단어 : 신세포암, 췌장전이, 췌장절제술 Received: Accepted: 서론 신세포암은비교적드문질환으로 2002년한국중앙암등록사업연보고서에의하면전체암의약 2% 를차지한다. 1 하지만, 진단기술의발달에도신세포암의약 1/3은진단당시부터이미전이성암으로발견되며, 국소성암으로근치적수술을받았다할지라도약 20-40% 정도는재발을경험하게된다. 2 신세포암의전이가빈발하는장기로는폐, 뼈, 간, 뇌와부신등이있으나드물게는방광, 피부, 췌장등으로전이되기도한다. 3,4 췌장으로의전이성종양은전체췌장암의 5% 이하를차지할정도로일반적이지으며, 5,6 특히, 신세포암의췌장전이는매우드문것으로알려져있다. 7 하지만, 신세포암의전이성췌장암의경우원발성췌장암보다수술적절제를했을때예후가더좋다는보고가많아, 신세포암을진단받은경력이있는환자에서원발성췌장암과신세포암의전이성병변을구별하는것이중요하다. 109

2 한국간담췌외과학회지 : 제 13 권제 2 호 2009 현재까지신세포암의췌장전이에대한여러보고는있었으나, 단편적인증보고가있을뿐이다. 따라서저자들은한기관에서경험한다수의신세포암췌장전이임상양상의특징과치료후생존률등을분석보고하고자한다. 대상및방법 환자에서신세포암의췌장전이진단시전신쇠약감과흑색변을호소하였으나, 3명의환자는무증상으로주기적외래추적검사상우연히발견하였다. 췌장전이의위치로는췌장두부가 2명 (50%), 췌장체부가 1명 (25%) 그리고췌장체부및미부전이가 1명 (25%) 이었다. 신세포암치료후췌장전이까지의평균기간은 86.0개월 (±57.6 개월 ) 이었으며, 신세포암의췌장전이로진단받은환자들의임상적특징은표 1과같다. 1986년 1월부터 2008년 8월까지연세대학교의과대학외과학교실에서췌장절제술을시행받은 1,415명의환자를대상으로연구를시행하였다. 대상기간동안 4명 (0.2%) 의환자가신세포암의췌장전이를진단받았으며 4명의환자를대상으로후향적연구를시행하였다. 환자들의외래추적검사는이학적검사, 영상진단학적검사 ( 흉부 X-ray 및복부컴퓨터단층촬영 ) 및임상병리학적검사를기본적으로시행하였다. 모든환자들의외래추적검사, 임상병리학적검사및영상진단학적검사는 3개월간격으로시행하였다. 특히전이가발견되었을때는다른기관의전이병소를찾기위하여그에요한검사 (Bone scan, Chest CT, PET등 ) 를시행하였다. 환자들의생존여부는병력기록지, 전화탐방으로조사하였으며마지막추적일은 2008년 12월 31일이었다. 2) 진단과치료방법대상환자 4명중 3명의환자에서췌장병변의진단을위해술전조직검사를시행하였으며, 모두전이성신세포암으로진단받았다. 췌장전이치료는모든환자가췌장절제를시행하였으며, 2명의환자에서는췌두부이지장절제술, 2명의환자에서는원위부췌미부절제술을시행하였으며그중한명의환자에서는복강경원위부췌미부절제술을시행하였다. 3) 병리소견절제된췌장의육안소견에서전이병소들의평균크기는 2.7cm 이었으며, 임파선전이는없었다. 현미경소견에서임파선, 혈관침윤이없는세포사이가명확한전형적인투명세포형의전이성신세포암이관찰되었다. (Figure 1) 결과 1) 환자군의특성대상환자 4명의평균연령은 58.7세 (±10.5세) 까지이었으며, 이중남자가 2명, 여자는 2명이었다. 한명의 4) 치료경과대상환자들의평균생존기간은 109개월 (± 67.3 개월 ) 이었다. 특히 2명의환자에서는췌장전이수술후폐전이가발견이되어면역화학요법을시행하였다. 한명은다발성폐전이로인터페론 (INF-a) 치료후폐전이후 12개월째사망하였고, 또다른한명의환자는면역화학요법치료후폐좌하엽쐐기절제술받고추적관찰중잔여췌장주변에재발소견보여현재 Sorafenib 치료중이다. Table 1. Clinical Characteristics of the 4 patients treated for pancreas metastasis from Renal cell carcinoma Patients Sex Age Status of RCC Interval Status of pancreas metastasis 2 nd recurrence Survival Survial (yr) Site TNM stage (months) Site Treatment Site Treatment (months) 1 F 74 Lt II 18 Body and tail Lapa-DP None No 10 Alive 2 M 57 Rt I 140 Head PD Lung INF-α 159 Dead 3 M 51 Lt I 59 Head PPPD Lung IL-2, INF-α 127 Alive 4 F 53 Lt II 127 Body DP None None 140 Alive Interval: Interval indicates the duration between treatment of primary RCC and the diagnosis of pancreas metastasis, Lapa-DP: Laparoscopic distal pancreatectomy, PD: Pancreaticoduodenectomy, PPPD: Pylorus preserving pancreaticoduodenectomy, DP: Distal pancreatectomy 110

차장호외 : 단일기관에서경험한신세포암의췌장전이치료경험 고찰 신세포암은한국중앙암등록사업연보고서에의하면대한민국전체암등록의 2% 정도를차지한다.

7,8 기신세포암의경우 5년생존률이 90% 로예후가좋은암이지만, 9,10 한번전이가된경우 5년생존율은 10% 에서 15% 이하로낮아진다.

5 Roland 등 5 이보고한바에의하면췌장악성종양의 2% 만이전이성병변이라고보고하였으며, Klugo 등 14 은전이성신세포암환자에서약 2.8% 에서췌장전이를한다고보고하였다.

하지만, Tongio등 15 은신세포암췌장전이환자의 60% 가위장관출혈증상을보였다고보고하였고, 본연구에서도대상환자 4명중 1명 (25%) 에서위장관출혈이있었다. 하지만, 대부분의경우증상없이외래추적관찰중방사선학적검사상우연히발견된경우가대부분이다.

3 차장호외 : 단일기관에서경험한신세포암의췌장전이치료경험 고찰 신세포암은한국중앙암등록사업연보고서에의하면대한민국전체암등록의 2% 정도를차지한다. 1 진단기술의발달에도신세포암환자중약 20-30% 가발견당시타장기에전이된소견을보이며근치적신장절제술을시행했다할지라도 25% 의환자가 5년내에전이소견을보인다. 7,8 기신세포암의경우 5년생존률이 90% 로예후가좋은암이지만, 9,10 한번전이가된경우 5년생존율은 10% 에서 15% 이하로낮아진다. 11,12 신세포암이호발되는전이부위는폐실질, 뼈, 간과뇌이지만, 13 갑상선, 췌장, 골격근, 피부그리고연부조직포함한다른장기로도드물지만전이를하는것으로알려져있다. 췌장은다른악성종양으로부터전이가매우드문장기로전이성암은췌장암전체의 5% 이하를차지한다. 5 Roland 등 5 이보고한바에의하면췌장악성종양의 2% 만이전이성병변이라고보고하였으며, Klugo 등 14 은전이성신세포암환자에서약 2.8% 에서췌장전이를한다고보고하였다. 신세포암췌장전이의증상은일반적인췌장암과마찬가지로복통, 복부불편감, 위장관출혈, 담관폐쇄, 체중저하, 피로감과황달등의증상이있을수있으나, 증상없이외래추적관찰결과우연히발견되기도한다. 하지만, Tongio등 15 은신세포암췌장전이환자의 60% 가위장관출혈증상을보였다고보고하였고, 본연구에서도대상환자 4명중 1명 (25%) 에서위장관출혈이있었다. 하지만, 대부분의경우증상없이외래추적관찰중방사선학적검사상우연히발견된경우가대부분이다. A B C D Fig. 1. Pathologic findings of the specimen of pancreas from renal cell carcinoma A. B. The gross appearance of the resected specimen of the pancreas. An about 2x2xm tumor occupy the body of pancreas C, At lower power view of the pancreas, an intraluminal mass (x 100) D. Higher magnification showing tumor cells with clear, abundant cytoplasm consistent with metastatic renal cell carcinoma (x200) 111

4 한국간담췌외과학회지 : 제 13 권제 2 호 2009 영상의학적으로신세포암의췌장전이는음파상저음영으로보이며, 복부전산화단층촬영에서는췌관의확장여부와관계없이보통조영증강을보이는종괴소견을보이는것으로알려져있다. 16 우리의경우에도췌장전이병변은복부전산화단층촬영에서조영증강을보이는종괴소견을보여전형적인췌장암과감별진단이용이하였다. 신세포암은일반적으로항암화학요법이나방사선치료에발반응하지는것으로알려져있으며, 7 단지 IFN-a등을이용한면역요법이진행형신세포암에서유일하게치료효과가있는것으로입증되었으나그효과도미비하다. 2 최근에는 bevacizumab이나 sunitinib 등을이용한병합표적치료등이시도되어지고있으나안정성과효용성등은아직좀더연구되어야할것으로보인다. 17 신세포암은단독으로췌장전이를보이는가장흔한원발성종양이고신장적출술후오랜기간이지난후에발생할수있으며, 췌장전이시췌장절제술후예후가좋은것으로보고되고있다. 18,19 우리경우에도신세포암으로신장적출술후췌장재발의평균기간은 86개월이었으며최대신장수술후 10여년이지난경우에도췌장으로의전이가발생되었다. 따라서, 신세포암의경우신적출술시행후재발이없다할지라도 10년이상동안주기적인외래추적관찰이요하다고사료된다. 신세포암의췌장전이시원발성췌장암에비하여예후가좋은것으로알려져있으며, 26 우리의경우에는증가적어원발성췌장암과비교할수는없었지만평균생존기간은 109개월로원발성췌장암보다좋은결과를보이고있다. 본연구의경우수술적절제가가능한췌장전이병소일경우적극적인수술적치료로장기생존을기대할수있다는것을알수있었다. 따라서수술요법과함께면역화학요법을포함한적극적치료를시행한다면전이성신세포암환자에서도보다좋은예후를기대할수있다고사료된다. 결론 신세포암의췌장전이는드물지만기의병변에서도신장적출후오랜기간이지난뒤발병할수있다. 특히, 전이성신세포암일경우특히, 췌장전이에대한치료는적극적인췌장절제와함께적극적인면역화학요법이시행된다면장기적인생존을기대할수있다고사료된다. 참고문헌 1. Ministry of Health and Welfare, Republic of Korea annual report of the Korea Central Cancer Registry, Motzer R, Ruso P. Systemic therapy for renal cell carcinoma. J Urol 2000;163: Dayal H, Kinman J. Epidmiology of kidney cancer. Semi Oncol 1983;10: Celebi I, Guzelsoy M, Yorukoglu K. Renal cell carcinoma with gallbladder metastasis. Int J Urol 1998;5: Roland CF, van Heerden JA. Nonpancreatic primary tumors with metastasis to the pancreas. Surg Gynecol Obstet. 1989;168: Faure JP, Tuech JJ, Richer JP, et al. Pancreatic metastasis of renal cell carcinoma: presentation, treatment and survival. J Urol. 2001;165: Kasabian A, Stein J, Jabbour N, et al. Renal cell carcinoma metastatic to the pancreas: a single-institution series and review of the literature. Urology. 2000;56: Karimi KM, McFadden DW, et al. Pancreatic resection for metastatic renal cell carcinoma to the pancreas. Am Surg. 2007;73: Javidan J, Stricker HJ, Tamboli P, et al. Prognostic significance of the 1997 TNM classification of renal cell carcinoma. J Urol 1999;162: Pantuck AJ, Zisman A, Belldegrun AS. The changing natural history of renal cell carcinoma. J Urol 2001;166: Janzen NK, Kim HL, Figlin RA, et al. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am 2003;30: Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med 1996; 335: Ritchie AWS, Chisholm GD. The natural history of renal carcinoma. Semin Oncol 1983;10: Klugo RC, Detmers M, Stiles RE, et al. Aggressive versus conservative management of stage IV renal cell carcinoma. J Urol 1977;118: Tongio J, Peruta O, Wenger JJ, et al. Metastases duodenales et pancreatiques du nephro-epithel iome: a propos dequatre observations. Ann Radiol 1977;20: Hirota T, Tomida T, Iwasa M, et al: Solitary pancreatic metastasis occurring eight years after nephrectomy for renal cell carcinoma: a case report and surgical review. Int J Pancreatol 1966;19: Reeves DJ, Liu CY.Cancer Chemother Pharmacol. 2009;64: Robbins EG, Franceschi D, and Barkin JS: Solitary metastatic tumors to the pancreas: a case report and review of the literature. Am J Gastroenterol 1996;91: Bassi C, Butturini G, Falconi M, et al. High recurrence rate after atypical resection for pancreatic metastases from renal cell carcinoma. Br J Surg 2003;90: Thompson LD, Heffess CS. Renal cell carcinoma to the pancreas insurgical pathology material. Cancer. 2000;89: Sohn TA, Yeo CJ, Cameron JL, et al. Renal cell carcinoma 112

5 차장호외 : 단일기관에서경험한신세포암의췌장전이치료경험 metastatic to the pancreas: results of surgical management. J Gastrointest Surg. 2001;5: Law CH, Wei AC, Hanna SS, et al. Pancreatic resection for metastatic renal cell carcinoma: presentation, treatment, and outcome. Ann Surg Oncol. 2003;10: Z graggen K, Fernandez-Del Castillo C, Rattner DW, et al. Metastases to the pancreas and their surgical extirpation. Arch Surg. 1998;133: Sperti C, Pasquali C, Liessi G, et al. Pancreatic resection for metastatic tumors to the pancreas. J Surg Oncol. 2003;83: Zerbi A, Ortolano E, Balzano G, et al. Pancreatic metastasis from renal cell carcinoma: which patients benefit from surgical resection? Ann Surg Oncol Apr;15: Tolia BM, and Whitmore WF: Solitary metastasis from renal cell carcinoma. J Urol 1975;114:

김범수

김범수 Analysis of Outcomes after Resection of Sarcomatous Hepatocellular Carcinoma Purpose: Sarcomatous hepatocellular carcinoma (HCC) is rare. Therefore, the clinicopathologic characteristics and prognosis