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1 대한소화기학회지 2010;56:54-58 DOI: /kjg 스텐트삽입과항암요법후근치적절제술을시행했던폐쇄성국소침윤공장선암 1 예 순천향대학교의과대학내과학교실 김형기ㆍ고봉민ㆍ박종규ㆍ홍수진ㆍ문종호ㆍ이준성ㆍ이문성ㆍ김부성 A Case of Locally Invasive Obstructive Jejunal Cancer with Curative Resection after Stenting and Chemotherapy Hyung Ki Kim, M.D., Bong Min Ko, M.D., Jong Kyu Park, M.D., Su Jin Hong, M.D., Jong Ho Moon, M.D., Joon Seong Lee, M.D., Moon Sung Lee, M.D., and Boo Sung Kim, M.D. Department of Internal Medicine, Soon Chun Hyang University School of Medicine, Bucheon, Korea Small bowel adenocarcinoma is a relatively rare malignancy. In Korea, 13.1% of small bowel adenocarcinoma occurs in the jejunum. The absence of effective screening methods and relatively obscure symptoms contribute to the higher percentage of advanced cases at the time of diagnosis. Although curative resection is the mainstay of treatment, it is often impossible. Chemotherapy and radiotherapy have shown a disappointing treatment result for advanced staged small bowel adenocarcinoma. We report a 54-year-old woman with locally invasive jejunal cancer who underwent curative resection after stent insertion with enteroscopy and chemotherapy. (Korean J Gastroenterol 2010;56:54-58) Key Words: Jejunal neoplasm; Stents; Chemotherapy 서론소장은위장관길이의 75% 를차지하지만소장에서의악성종양발생은드물다. 2002년국가암등록사업보고서에서소장선암의발생률은 0.5% 를차지하며, 이중 13.1% 가공장에서발생한다고보고하였다. 1 일반적으로소장에서발생하는악성종양의증상은상하부위장관종양의증상과유사하여, 증상발현부터평균 6-8개월후에진단되고, 출혈이나장폐쇄를동반하는경우가많다. 대부분진행된상태에서발견되어완치적수술이불가능한경우가많고, 장폐쇄등에의한환자의전신적상태악화로근치적치료가어려 울때가있다. 저자등은주변장기전이가있는공장선암에서항암제치료도중발생한악성소장폐쇄를소장내시경을이용하여담도용스텐트를삽입하였고항암치료에반응이있어근치적절제술을시행한증례를경험하여문헌고찰과함께보고한다. 증례 54세여자가상복부통증을주소로내원하였다. 과거력에서당뇨, 고혈압투약중이며내원 1년전부터다약제내성폐결핵을진단받아투약중이었다. 환자는내원 2년전부터 접수 : 2009 년 11 월 10 일, 승인 : 2010 년 2 월 26 일연락처 : 고봉민, , 경기도부천시원미구중동순천향대학교부천병원내과소화기센터 Tel: (032) , Fax: (032) kopa9445@schbc.ac.kr Correspondence to: Bong Min Ko, M.D. Institude for Digestive Center, Department of Internal Medicine, Bucheon Hospital, Soonchunhyang University, 1174, Jungdong, Wonmi-gu, Bucheon , Korea Tel: , Fax: kopa9445@schbc.ac.kr
2 김형기외 7 인. 스텐트삽입후치료한폐쇄성공장선암 1 예 55 Fig. 1. (A) Endoscopically, the stomach showed surrounding edematous mucosa and central erosion with extrinsic compression on the posterior wall of the upper body. (B) Exophytic low density mass in the duodenum with direct invasion to the stomach and colon in the abdominal computed tomography. (C) Small bowel enteroscopy showed encircling ulcerating mass on the jejunum. (D) The jejunum biopsy indicated moderately differentiated adenocarcinoma (H&E stain, 100). 간헐적상복부통증이있어보존적치료로지내오다당일구토가동반된상복부통증이심해져내원하였다. 내원당시활력증후는혈압 130/90 mmhg, 맥박 85회 / 분, 호흡수 20회 / 분, 체온 36.6 o C이었다. 복부진찰에서상복부에손바닥크기의종괴가만져졌으며압통은있으나반발통은없었다. 내원당일시행한말초혈액소견은백혈구 11,200/mm 3, 혈색소 5.0 g/dl, 혈소판 373,000/mm 3 이었으며, 혈청생화학검사는 AST/ALT 21/12 IU/L, Alkaline phosphatase 62 IU/L, Total bilirubin 0.31 mg/dl, BUN 7 mg/dl, 크레아티닌 0.9 mg/dl, AFP 2.6 ng/ml, CEA 1.63 ng/ml이었다. 내원다음날시행한상부위장관내시경소견에서체부후벽에전반적인점막부종및중앙부에미란을동반한외부압박에의한병변이관찰되었다 (Fig. 1A). 복부전산화단층촬영에서는공장고리선단부위에인접하여경계가불분명하고내부에심한괴사와공기를포함하는종괴가있으며, 주위에있는위후벽과대장의비장만곡부를침범하는양상이관찰되었다. 인접공장과십이지장벽의비후, 주변에종괴의심한지방침윤등이보였고문맥혈전증과비장에여러개의경색소견, 복수가있었으나간에는특이소견은없었다 (Fig. 1B). 공장병변을확인하기위해이중풍선소장내시경을경구로시행했으며십이지장을지나약 100 cm 부근에서표면이삼출물로뒤덮이고, 대부분의내강을폐쇄 하는궤양을동반한종괴가있어 (Fig. 1C) 조직검사를시행하여중등도분화도를보이는선암종으로진단되었다 (Fig. 1D). FDG- PET (positron emission tomography) 에서공장기시부에 FDG 섭취가 SUV 7.2로증가되어있었고위상부체부후벽에서도 FDG 섭취가 SUV 8.6로증가되었다. 내원 1개월후부터 FOLFOX요법 (5-FU 1500 mg, leukovorin 300 mg, oxaliplatin 90 mg) 을 2주마다 6회시행하였고, 방사선요법은 28회를계획하였으나 7회를실시한이후전신상태의악화로추가로시행하지못했다. 4개월후오심, 구토증상이발생하였고방사선촬영에서소장폐색의심하여밀기방식소장내시경을이용하여유도선을삽입한후내시경을통한 (through the scope, TTS) 위장관용스텐트삽입을시도했으나예각으로인해실패하고비막형담도용스텐트를삽입하였다 (Fig. 2A). 스텐트삽입후환자는증상호전을보여추가로 6회의항암요법을시행하였으며스텐트삽입 4주째시행한복부단순촬영에서원위부로의일탈을보여주었지만증상의변화는없었고이후스텐트는자연배출되었다. 7개월후시행한복부전산화단층촬영에서종괴의크기가매우감소하였고인접한위와대장비장만곡부의벽비후및주위지방과혈관침윤은현저히감소하였다. 또한이전에관찰되었던비장경색과복수는보이지않았고새로생
3 56 The Korean Journal of Gastroenterology: Vol. 56, No. 1, 2010 Fig. 2. (A) Stent was inserted on the jejunal obstruction site by push enteroscopy. (B) Abdominal computed tomograpy on the follow up showed markedly decreased size and invasiveness of jejunal cancer. Fig. 3. The jejunal specimen after jejunal segmental resection showed marked fibrosis, necrosis, and chronic inflammation without residual cancer (H&E stain, A: 20, B: 100). 긴병변은없었다 (Fig. 2B). 내원 8개월후공장분절절제술을시행했으며현미경검사결과종양병변에서는완전괴사된조직 (Fig. 3) 만이관찰되었고주위림프절전이는발견되지않았다. 수술 1개월후상부위장관내시경에서위에서는특이소견을보이지않았으며현재추적관찰중이다. 고찰소장선암은매우드문악성종양으로발생빈도, 예후나항암요법의역할이불분명하다. 국내의소장악성종양발생율은 0.5% 이며이중 13.1% 가공장에서발생했다. 1 이질환은점점증가추세에있는데크론병, 2 가족성선종성용종증, 3,4 유전성비용종증대장암 5 과관련있는것으로보고있다. 나쁜예후인자로는 75세이상, 수술적절제를못했을 경우, 십이지장에발생한경우, 진단이늦은경우등이다. 6 조직학적분화도가중등도이상인경우는미만인경우에비해생존기간이길었고 (43% vs. 0%) 장막침범은예후에영향이없었다. 7 림프절전이가예후에미치는영향에대해서논의의여지가있지만림프절전이유무에따른 5년생존율은 13% 와 70% 였다. 8 National Cancer Data Base (NCDB) 보고에서소장선암의 5년생존율은 30% 였으며, 평균생존기간은국소적종양의경우 50.1개월, 국소적으로침윤된종양은 22.2개월, 원격전이가동반된경우는 8.6개월이었다. 공장에발생한소장암의경우 5년생존율은 37.6%, 평균생존기간은 28.9개월이었다. 6 소장선암의근치적절제여부는환자의생존과예후에중요한영향을미치는인자이지만상당수의환자에서근치적절제가불가능하다. Czaykowski와 Hui 9 에의하면 60% 의
4 Kim HK, et al. A Case of Obstructive Jejunal Cancer with Curative Resection after Stenting and Chemotherapy 57 환자에서고식적치료만이가능했고 Dabaja 등 10 은환자의 33% 에서수술이불가능했다고보고했다. NCDB 보고 6 에서는불량한전반적상태와진행된병기에의해환자의 33.4% 는비수술적방법으로치료했고대부분항암치료를받았다. 고식적항암치료의역할에대해서는아직까지연구결과가많지않아약제선택에제한이있다. 1984년 Jigyasu 등 11 은 5-FU를기본으로치료했던 14명의환자에서평균 9개월의생존기간을, Crawley 등 12 은 5-FU 사용군에서 37% 의전반적반응비율과 7.8개월의평균무진행생존기간 (median progression free survival) 을보고하여소장선암이 5-FU에대해민감하고고식적수술이상의임상적효과가있다고주장하였다. Ouriel과 Adams 8 는 stage IV인환자에서 5-FU을기본으로한항암화학요법을시행했을때평균생존기간이 10.7개월로치료하지않은군에비해 4개월의생존기간연장을보고했고, Dabaja 등 10 은수술이불가능했던환자에서항암화학요법을시행했을경우생존기간은 12개월로대조군의 2개월에비해유의한차이를보고하여 (p=0.02) 전이가있거나재발한환자에서항암화학요법의임상적의의를제시하였다. 소장암의항암화학요법에대한기존보고들을정리한문헌에의하면 5-FU와 gemcitabine을같이사용한경우반응률은 33% 로증가하였고, irrinotecan을기본으로한항암요법의경우 42% 의반응률을보고하였다. 13 새로운약제를이용한항암치료가시도되고있지만대규모연구나전향연구는부족한실정이다. 항암화학요법과방사선치료을병합할경우평균무진행생존기간이 8개월로생존률증가는없었고심한부작용을보고하였다. 14 수술전항암요법이나방사선치료을동시에시행할경우십이지장암에서병리학적반응이나생존율에긍정적효과가있다는보고가 14 있으나공장암에서는이에대한연구가없다. 소장암에서 FOLFOX 요법에의해관해가유도되었다는보고는없으나 15 oxaliplatin 기본으로한복합항암치료를시행한 4예중 2예에서안정 (stable disease) 상태를보고한연구가있어본환자에서상기항암치료를선택하였다. 소화관의악성폐쇄병변에서고식적수술적우회술에비해스텐트삽입술의치료성적이우월하다. 수술적우회술은환자의전신상태가비교적좋고상대적으로느리게진행하는질환이거나기대여명이 60일이상일경우고려해볼수있다. 공장이하부위의폐쇄혹은여러부위에병변이있는경우는내시경적스텐트의성공률이낮아수술적치료를고려하지만, 16 최근소장내시경술발달로내시경적방법으로치료한경험들이보고되고있다. 17,18 이번증례는병변의진단을위해이중풍선소장내시경을이용하였고, 병변이근위부공장에있었기때문에밀기 방식소장내시경을이용하여스텐트를삽입했다. 폐쇄병변이예각으로심하게꺾여있어일반적위장관용스텐트삽입이어려워유연한비막형담도용스텐트를삽입한후폐쇄증상이호전되고유동식의섭취가가능했다. 스텐트삽입후폐쇄의재발및천공등의합병증은없었고삽입 4주후에발생한일탈은항암제효과에의한종양크기감소로발생했을것이라판단된다. 따라서스텐트삽입술은항암치료에반응을보이기까지폐쇄증상을해결할수있는가교역할을했다고볼수있다. 저자들은국소적침범으로인한소장폐쇄를스텐트를이용하여폐쇄증상의완화를보였고항암제및방사선치료등을이용하여종양의호전을보여근치적수술을할수있었던공장선암 1예를경험하였기에문헌고찰과함께보고하는바이다. 참고문헌 1. Korea Central Cancer Registry Annual report of the korea central cancer registry (based on registered data from 139 hospitals) Greenstein AJ, Sachar DB, Smith H, Janowitz HD, Aufses AH Jr. A comparison of cancer risk in Crohn's disease and ulcerative colitis. Cancer 1981;48: Offerhaus GJ, Giardiello FM, Krush AJ, et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology 1992;102: Jagelman DG, DeCosse JJ, Bussey HJ. Upper gastrointestinal cancer in familial adenomatous polyposis. Lancet 1998;21: Rodriguez-Bigas MA, Vasen HF, Lynch HT, et al. Characteristics of small bowel carcinoma in hereditary nonpolyposis colorectal carcinoma. International Collaborative Group on HNPCC. Cancer 1998;83: Howe JR, Karnell LH, Menck HR, Scott-Conner C. Adenocarcinoma of the small bowel: review of the national cancer data base, Cancer 1999;86: Stemmermann GN, Goodman MT, Nomura AM. Adenocarcinoma of the proximal small intestine. A marker for familial and multicentric cancer? Cancer 1992;70: Ouriel K, Adams JT. Adenocarcinoma of the small intestine. Am J Surg 1984;147: Czaykowski P, Hui D. Chemotherapy in small bowel adenocarcinoma: 10-year experience of the British Columbia Cancer Agency. Clin Oncol (R Coll Radiol) 2007;19: Dabaja BS, Suki D, Pro B, Bonnen M, Ajani J. Adenocarcinoma of the small bowel: presentation, prognostic factors, and outcome of 217 patients. Cancer 2004;101:
5 58 대한소화기학회지 : 제 56 권제 1 호, Jigyasu D, Bedikian AY, Stroehlein JR. Chemotherapy for primary adenocarcinoma of the small bowel. Cancer 1984;53: Crawley C, Ross P, Norman A, Hill A, Cunningham D. The Royal Marsden experience of small bowel adenocarcinoma treated with protracted venous infusion 5-fluorouracil. Br J Cancer 1998;78: Coia L, Hoffman J, Scher R, et al. Preoperative chemoradiation for adenocarcinoma of the pancrease and duodenum. Int J Radiat Oncol Biol Phys 1994;30: Abrams RA, Grochow LB, Chakravarthy A, et al. Intensified adjuvant therapy for pancreatic and periampullary adenocarcinoma: survival results and observations regarding patterns of failure, radiotherapy dose and CA-19-9 levels. Int J Radiat Oncol Biol Phys 1999;44: Fishman PN, Pond GR, Moore MJ, et al. Natural history and chemotherapy effectiveness for advanced adenocarcinoma of the small bowel: a retrospective review of 113 cases. Am J Clin Oncol 2006;29: Ripamonti CI, Easson AM, Gerdes H. Management of malignant bowel obstruction. Eur J Cancer 2008;44: Yamamoto H, Kita H, Sunada K, et al. Clinical outcomes of double balloon endoscopy for the diagnosis and treatment of small intestinal diseases. Clin Gastroenterol Hepatol 2004; 2: Kita H, Yamamoto H, Yano T, et al. Double balloon endoscopy in two hundred fifty cases for the diagnsis and treatment of small intestinal disorders. Inflammopharmacology 2007;15:74-77.
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