Korean Journal of HBP Surgery 원 저 Vol. 5, No., February ICGR5 가 % 이상인간세포암환자에서대량간절제술에따른술후간부전의예측인자 Major Hepatectomy in the HCC Patient with an Indocyanine Green Retention Rate at 5 Minutes of % or Higher: Predictive Values of Postoperative Hepatic Failure Purpose: Major hepatic resection is sometimes inevitable in patients with impaired liver function. We evaluated risk factors that cause postoperative liver failure after major hepatic resection in patients with over a % Indocyanine Green Retention rate at 5 minutes (ICGR5). Methods: From Apr. to Aug. 9, 3 patients who had over a % rate of ICGR5 underwent major hepatic resection ( 4 Couinaud segments). Among the 3, 9 patients showed postoperative liver failure (less than 5% prothrombine time and/or 5 mg/dl or higher of total bilirubin). This high-risk group was compared to the rest who constituted a low-risk group. Results: Patients with esophageal varix were more common in the high risk group (4 versus, p=.43). Other clinicopathologic features showed no difference between the two groups. We had in-hospital deaths in the high risk group. Conclusion: Great care is needed in patients with esophageal varix and limited liver function during major hepatic resection. 이채윤, 황윤진, 천재민, 권형준, 손준호, 김상걸, 윤영국 경북대학교병원외과 Chae Yoon Lee, M.D., Yoon Jin Hwang, M.D., Jae Min Chun, M.D., Hyung Joon Kwon, M.D., Joon Ho Son, M.D., Sang Gul Kim, M.D., Yung Kook Yun, M.D. Department of Surgery, Kyungpook National University Hospital 책임저자 황윤진대구시중구삼덕동 가 5 경북대학교병원외과우편번호 7-7 Tel: 53-4-58 Fax: 53-4-5 E-mail: yjhwang@mail.knu.ac.kr Key Words : Hepatocellular carcinoma, Hepatectomy, Hepatic failure, Esophageal varix 중심단어 : 간세포암, 간절제술, 간부전, 식도정맥류 Received:. 8. 4 Accepted:.. 4 서론 간세포암의근치적치료법으로는수술절제, 간이식, 국소치료술등이있다. 간이식은경변간에발생한간세포암의치료에있어손상된간기능을동시에회복시킬수있다는점에서가장이상적인치료법이지만, 고비용과공여자가부족의문제로절제가능한간세포암의경우간절제술이다른치료법에우선한다. -7 간절제술은최근수술술기의발달과술전후 환자관리의발달로인해낮은수술사망률의안전한수술이며, 현재가능한간세포암치료법중가장효과적인치료법이다. 그러나간세포암환자의대부분이만성간질환등을동반하고있어간절제후사망의주된원인인간부전의발생의예방을위해술전잔류간기능검사가중요하며이를위해여러가지방법들이고안되었다. 이중 Indocyanine Green (ICG) 의 5분후의정체율 (ICGR5) 은간절제술을시행할환자의선별및간절제술의절제범위의결정에있어널리사용되는잔류간기능검사이다. 8-3 간우엽절제술및 4분절이상의간절제술
한국간담췌외과학회지 : 제 5 권 호 시행에있어 ICGR5 % 는술후간부전을피할안전경계로알려져있으나, 그상한선은논쟁의여지로남아있다. 4,5 본연구는술전 ICGR5가 % 이상인환자에서간우엽절제술및 4분절이상의간절제술후간부전및술후사망의예측인자들에대해평가하고자한다. 방법 년 4월에서 9년 8월까지경북대학교병원에서간세포암으로진단된환자중술전 ICGR5가 % 이상이며, 4분절이상의대량간절제술 ( 우엽절제술, 확대우엽절제술, 우삼분절절제술및확대좌엽절제술 ) 을시행한 3명의환자를대상으로하였다. 술후프로트로빈시간 (Prothrombine time) 이 5% 미만이거나술후한차례이상총빌리루빈값 (Total bilirubin) 이 5 mg/dl 이상이었던 9명의환자들을고위험군, 이외 3명의환자들을저위험군으로분류하여각각의임상병리학적특징, 수술소견및영상학적소견등을의무기록검토, 혈액검사및복부전산단층촬영사진확인등을통해후향적으로조사하였다. 술전관련인자는성별, 나이, B형간염및 C형간염의유무, ICGR5, 혈소판수치, 복부전산단층촬영사진상종양의크기및개수, 식도정맥류의유무, 프로트롬빈시간, 혈청알부민 (albumin), 총빌리루빈, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) 를분석하였다. 술중관련인자는술중출혈량, 수혈여부, 간헐적간유입혈류차단시간, 수술시간및시행절제술을분석하였다. 술후관련인자는술후재원기간, 합병증및사망률을분석하였다. 통계분석은 SPSS (Version.) 프로그램을이용하였으며, 연속변수와비연속변수는각각 Student s t test와 Chi-square test 를이용하여 p<.5일때유의한것으로판단하였다. 결과 전체 3명의환자중남자는 3명 (9.9%), 여자는 명 (3.%) 이었으며수술당시평균나이는고위험군에서 58.33±.세, 저위험군에서.9±8.8세로차이가없었다. B형간염은저위험군 3명중 3명, 고위험군 9명중 5명으로차이가없었으며, C형간염또한저위험군 5명, 고위험군 3명으로유의한차이가없었다. ICGR5는저위험군에서 5.5±., 고위험군에서.7±.9로통계학적유의성이없었으며, 술 전복부단층촬영사진소견에따른종양의개수및크기, 간절제량에따른차이는없었다. 고위험군에서 4명의환자가식도정맥류가있었으며저위험군 명과비교하여통계학적유의성이있었다 (p=.43). 프로트롬빈시간, 알부민 (albumin), 총빌리루빈, AST/ALT 분석에서고위험군과저위험군간의통계학적유의성은발견되지않았다 (Table ). 수술방법은우엽절제술 명 ( 고위험군 : 명, 저위험군 : 5명 ), 확대우엽절제술 명 (명, 4명 ), 우삼분절절제술 명 ( 저위험군 ) 이었고확대좌엽절제수술이 4명 (3명, 명 ) 이었다. 술중출혈량은각각 89.7±.47 ml,.4±59.53 ml, 수술시간은 47± 44.4분, 43.33±.5분으로두군간의차이가없었다 (Table ). 평균재원기간은각각 5.3±9.7일,.4±5. 일로차이가없었으며병리조직소견 ( 만성간염, 간경병증 ) 에따른차이역시보이지않았다 (Table 3). 수술후합병증은두군간차이가없었으며고위험군에서간부전및다발성장기부전에의한 명의사망례가있었다 (Table 4). 고찰 일반적으로간세포암종은수술절제가다른치료법에비해우선하며이에따라술전간기능평가와술후잔류기능성간실질의크기와보존의예측은수술적위험도를최소화하기위해우선적으로중요하다. 대표적인간기능분류법인 Child- Pugh 분류는간경변증과정맥류출혈이있는환자에서문정맥단락수술후사망률과유병률을구하기위해고안되었으며현재까지도간절제술전평가에중요하게이용되고있다.,7 Child-Pugh 분류는총빌리루빈, 혈청알부민, 프로트롬빈시간, 복수의정도, 간뇌증의정도등의인자들로간기능을평가하는데, 복수나간뇌증의판단은주관적요소가될수있고나머지항목은다양한변화가가능하기에간기능을종합적으로평가하기에부족한점이있다. 실제간절제술후합병증을정확히예측하는데많은한계가있어 Child-Pugh A의간세포암종환자군에서도간절제술후 5% 이상에서비대상간기능상실을보였다는보고도있다. 8 Bruix 등 8 은정상문맥압이간절제술대상자를선택하는최선의척도로제시하였다. 바르셀로나그룹에서는 임상적으로의미있는문맥압항진증 을간정맥압기울기 (HVPG) 가 mmhg 이상에서내시경검사상식도정맥류가관찰되거나혹은비장비대와혈소판수치가, mm 3 이하인경우로정
이채윤외 :ICGR5 가 % 이상인간세포암환자에서대량간절제술에따른술후간부전의예측인자 Table. Comparison of preoperative variables between low risk group and high risk group in the high ICGR5 patient who Sex (M : F) Age (years) (mean±sd) HBs Ag (present/absent) Anti HCV Ab (present/absent) ICGR5* (%) (mean±sd) Platelet count ( 4 /μl)(mean±sd) Tumor volume on CT scan (cm 3 )(mean) Tumor size on CT scan (mm) (mean±sd) Tumor number (single/multiple) Esophageal varices (present/absent) Prothrombin time (%) (mean±sd) Albumin (g/dl) (mean) Total bilirubin (mg/dl) (mean±sd) AST (units/l) (mean±sd) ALT (units/l) (mean±sd) (n=3) : ±9 3/ 5/8 5.5±. (. 9.5) 79.4±. 4.9 5.±3. / / 9.3±. 3.9.8±.4 38.4±8. 8.8±9. Highrisk 9: 58± 5/4 3/.7±.9 (. 5.) 49.±5. 45. 49.3±5. 5/4 4/5 88.7±9.4 3.97.±.4 4.4±7. 4.4±9.4 *ICGR5=Indocyanine Green Retention rate at 5 minutes; High ICGR5=ICGR5 of % or higher.4.3.4.39.4.33.89.59.4.73.77..34.53 Table. Comparison of intraoperative variables between low risk group and high risk group in the high ICGR5 patient who (n=3) Highrisk Blood loss (ml) (mean±sd) Blood transfusion Intermittent hepatic inflow occlusion time (min) (mean±sd) Operation time (min) (mean±sd) Operation procedures Right hepatectomy Extended right hepatectomy Right trisectionectomy Extended left hepatectomy.4±59.5 48.±3.5 43.3±. 5 4 3 89.±.4 55.±5.7 47.±44..3.48.4.9 의하고, Child-Pugh A 환자군이라도 임상적으로의미있는문맥압항진증 이있는경우에는간절제술의적응에서제외할것을제안하였다. 9 간문맥압항진증의직접적인지표인 HVPG 측정은칩습적인검사라는제한점으로실제임상에서사용되지않고있으나, An 등 은간접적으로확인한문맥압항진증도침습적으로확인한 HVPG 상승처럼간세포암종수술후합병증과예후를반영하는인자로제시하였다. ICG 청정검사는간접적으로기능적간혈류와역학적간기능을평가하는상대적으로간단한검사이다. 여러방법들이술전간기능적보존평가에사용되었으나, 몇몇연구에서간절제술을시행할환자의선별에 ICG 청정검사가가장분별적인검사로보고되었다. -3 하지만 ICG 청정검사가부정확한경우도있다. ICG가담도계로분비되므로담도폐쇄가있을때 ICG 정체율의증가가예상될수있다. 3
한국간담췌외과학회지 : 제 5 권 호 Table 3. Comparison of postoperative variables between low risk group and high risk group in the high ICGR5 patient who (n=3) Highrisk Blood transfusion, postoperative (No) RBC transfusion (unit) FFP transfusion (unit) Background histology (No) Normal Chronic hepatitis Cirrhosis Resected volume (%) (mean±sd) Hospital stay (day) (mean±sd) Morbidity, case (rate%) Mortality, case (rate%) Cause of death.5 ( 5) 4.7 ( 3) 47.±4..±5. 7 (3.4%) (%) -.8 ( 7).3 ( 44) 7 47.9±9. 5.±9. 4 (44.4%) (.%) Hepatic failure....9.95.87.97.73 Table 4. Comparison of postoperative variables between low risk group and high risk group in the high ICGR5 patient who (n=3) Highrisk Complications (No) Pleural effusion Ascites Wound complication Bleeding Cardiac event Patients with complication Morbidity rate (%) Mortality rate (%) 7 (3.4%) /3 (34.4%) /3 (.3%) 3 4 (44.4%).97 용적측정과 ICG 청정검사를함께사용할경우각각을단독으로사용하는경우보다더나은지표를제공할것이다. 4 간용적측정을위해컴퓨터단층촬영을이용한최근연구에서간절제술은비종양간실질의 5% 이하를절제하는경우 ICGR5 % 미만의환자들에게용인되어진다. 5 앞으로이같은계열의연구들은수술을위한환자선별과술기선택에있어도움을줄것이다. 대량간절제술의경우근세기에술후간부전의높은위험인자로 ICGR5 4% 를안전제한으로정하여왔다.,3 Makuuchi 등 은복수가없고혈청빌리루빈이정상일때술전 ICGR5 수치를바탕으로간절제술의범위를결정하는표를제안하며, ICGR5 % 미만의환자에게간우엽절제술및 3엽절제술의 적응증이된다고제시하였다. 그러나술중출혈을줄이는매우신중한수술법과수술전후처치가동반된다면, 제한된간기능적보존을가진환자들이라도좋은간기능적보존을가진환자와유사한생존률과수술직후의좋은결과를얻을수있다. 4 좋은수술법과술후세심한관리가동반될경우제한된간기능적보존을가진환자에서환자선별은술후예후에영향을미치는또다른주요요인이다. Kubota 등 7 은술후프로트로빈시간이 5% 미만이거나, 총빌리루빈수치가 5. mg/dl 이상일때, 이를술후간부전이라정의하였다. 본연구에서는이를기준으로제한된간기능적보존에서간절제술을시행한환자들을고위험군및저위험군으로나누어술전, 술중및술 4
이채윤외 :ICGR5 가 % 이상인간세포암환자에서대량간절제술에따른술후간부전의예측인자 후관련인자들을비교하였다. 그결과대부분의인자에서통계적유의성을보이지않았으나, 식도정맥류는유의한인자로나타났다. 좋은술기와수술전후처치가가능하다해도제한된간기능적보존을가진환자에서식도정맥류를동반한경우수술후간부전이발생할수있어치료에대해깊은고찰이필요하겠다. 결 론 ICGR5 % 이상의제한된간기능적보존을가진환자에서 4분절이상의대량간절제시식도정맥류의여부는수술후간부전을예측할수있는인자로확인되며수술전평가를통해식도정맥류가존재할경우선별적절제가필요하고생각된다. 또한수술적절제시주의를요하며수술후세심한관리가필요하다. 참고문헌. Park JW; Korean Liver Cancer Study Group and National Cancer Center. Practice guideline for diagnosis and treatment of hepatocellular carcinoma. Korean J Hepatol 4;:88-98.. Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology 5;4:8-3. 3. Poon RT, Fan ST, Lo CM, et al. Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over years. Ann Surg ;34:3-7. 4. Cha CH, Ruo L, Fong Y, et al. Resection of hepatocellular carcinoma in patients otherwise eligible for transplantation. Ann Surg 3;38:35-3. 5. Belghiti J, Cortes A, Abdalla EK, et al. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg 3; 38:885-89.. Margarit C, Escartín A, Castells L, Vargas V, Allende E, Bilbao I. Resection for hepatocellular carcinoma is a good option in Child-Turcotte-Pugh class A patients with cirrhosis who are eligible for liver transplantation. Liver Transpl 5;: 4-5. 7. Majno P, Mentha G, Mazzaferro V. Resection, transplantation, either, or both? Other pieces of the puzzle. Liver Transpl 5;:77-8. 8. Caesar J, Shaldon S, Chiandussi L, Guevar L, Sherlock S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci 9;:43-57. 9. Takasaki K. Development of a method of estimating postoperative hepatic functions upon hepatectomy before the operation. J Jpn Surg Soc 978;79:5-534.. Takasaki T, Kobayashi S, Suzuki S, et al. Predetermining postoperative hepatic function for hepatectomies. Int Surg 98;5:39-33.. Okamoto E, Kyo A, Yamanaka N, Tanaka N, Kuwata K. Prediction of the safe limits of hepatectomy by combined volumetric and functional measurements in patients with impaired hepatic function. Surgery 984;95:58-59.. Yamanaka N, Okamoto E, Kuwata K, Tanaka N. A multiple regression equation for prediction of posthepatectomy liver failure. Ann Surg 984;:58-3. 3.Makuuchi M, Hasegawa H, Yamazaki S. Indication for hepatectomy in patients with hepatocellular carcinoma and cirrhosis (In Japanese). Shindan to Chiryo 98;74:5-3. 4. Lam CM, Fan ST, Lo CM, Wong J. Major hepatectomy for hepatocellular carcinoma in patients with an unsatisfactory indocyanine green clearance test. Br J Surg 999;8: -7. 5. Lang BH, Poon RT, Fan ST, Wong J. Perioperative and long-term outcome of major hepatic resection for small solitary hepatocellular carcinoma in patients with cirrhosis. Arch Surg 3;38:7-3.. Child CG III, Turcotte JG. Surgery and portal hypertension. In: Child CG III, editor. The Liver and Portal Hypertension. Philadelphia: Saunders; 94. 49-5. 7. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 973;:4-49. 8. Bruix J, Castells A, Bosch J, et al. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology 99;:8-. 9. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 999;3:434-44.. An M, Park JW, Shin JA, et al. The adverse effect of indirectly diagnosed portal hypertension on the complications and prognosis after hepatic resection of hepatocellular carcinoma. Korean J Hepatol ;:553-5.. Yamanaka N, Okamoto E, Toyosaka A, et al. Prognostic factors after hepatectomy for hepatocellular carcinomas. A univariate and multivariate analysis. Cancer 99;5:4-.. Fan ST, Lai EC, Lo CM, Ng IO, Wong J. Hospital mortality of major hepatectomy for hepatocellular carcinoma associated with cirrhosis. Arch Surg 995;3:98-3. 3. Lau H, Man K, Fan ST, Yu WC, Lo CM, Wong J. Evaluation of preoperative hepatic function in patients with hepatocellular carcinoma undergoing hepatectomy. Br J Surg 5
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