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1 A Practical Approach in Hepatocellular Carcinoma Surveillance Joong-Won Park Center for Liver Cancer National Cancer Center, Korea

2 간세포암종조기진단 (Early Detection) Screening 선별 Surveillance 감시 Recall 소환 Diagnosis Normal liver Chronic hepatitis Cirrhosis Lesions

3 간세포암종감시 - 소환 - 진단 - 추적 Recurrence Follow-up up 추적 Surveillance 감시 Recall 소환 Diagnosis After curative treatment Chronic hepatitis Cirrhosis Lesions

4 Inappropriate Using of the Term Screening/ Surveillance Screening 선별 Surveillance 감시 Recurrence Follow-up 추적 Recall 소환 Diagnosis Surveillance

5 National Cancer Screening Program of Korea

6 우리나라국가암조기검진프로그램요약 검진대상검진주기검진방법 위암 40세이상 ( 남녀공통 ) 매2년마다 위내시경검사또는위장관 조영술 간암 남자 30세, 여자 40세이상으로 B형또는 C형간염바이러스에의한만성간질환혹은기타간경변증등의간암발생고위험군 선별검사 (Screening) 매 6 개월마다 복부초음파검사및혈청알파태아단백검사 감시검사 (Surveillance) 대장암 50 세이상 ( 남녀공통 ) 매 1 년마다분변잠혈반응검사 선별검사 (Screening) 유방암 30 세이상 35 세이상 40 세이상 매월 2년간격 1-2년간격 자가유방검진의사의진찰의사의진찰및유방촬영 선별검사 (Screening) 선별검사 (Screening) 자궁경부암 30 세이상의모든여성매 2 년마다자궁질경부도말세포검사

7 간암조기진단을위한권고안 2001 대한간학회 - 국립암센터 목표간암발생위험이높은대상자에서정기적인검진을시행함으로써조기발견과적절한치료의기회를높여간암으로인한사망률을감소시키고생존기간을연장시키는것을목표로함 검진대상남자 30 세, 여자 40 세이상으로아래의위험인자를가지고있는대상자에게권고함 - B 형또는 C 형간염바이러스에의한만성간질환환자 - B 형간염바이러스표면항원과 C 형간염바이러스항체가모두음성인간경변및기타간암발생고위험군 검진방법 복부초음파검사와혈청알파태아단백 (AFP) 측정을 6 개월마다시행할것을권고함

8 AASLD Guideline: Surveillance for HCC Zhang BH, et al. J Cancer Res Clin Oncol 2004;130:417 Randomized Controlled Trial of Screening for HCC

9 AASLD Guideline: Surveillance for HCC If prevalence rate 5%, AFP >20 ng/ml PPV41.5% AFP>400 PPV 60% Trevisani F, J Hepatol 2001 Trevisani F, et al. Am J Gastro 2002 Not follow-up interval after treatment DN?

10 Impact of regererative, dysplastic nodules in HCC development LGDN, RN Borzio M, et al. J Hepatol 2003;208

11 Bruix J, Shermann M. Hepatology 2005 Surveillance and Recall Policies in Patients with higher risks of HCC Risk - HBV carrier male, age, cirrhosis, FHx, high DNA titer, ongoing hepatitis - Non-HBV cirrhosis Nodule + Large RN DN Surveillance Recall and diagnosis Follow-up After Tx interval tests interval tests interval tests 6-12 mo USG ±AFP?? 3-4 mo CT, MRI, Contrast US± Bx No consensus, Eminence-based

12 Bruix J, Shermann M. Hepatology 2005

13 National Cancer Screening Program of Korea

14 국가암조기검진사업 (NCSP): 간암 1. 검진대상 : 40 세이상 ( 남, 녀 ) 으로간경변증이나 B 형간염바이러스항원또는 C 형간염바이러스항체양성으로확인된경우 ( 단, 미확인자는 1 의방법으로확인하는것을원칙으로함 ) 2. 검진주기 : 6 개월 3. 검진방법 : 복부초음파검사 + 혈청알파태아단백측정 의료급여수급자 건강보험대상자소득수준하위 50% 40세이상이면서, 1. B형간염바이러스표면항원 (+) 2. C형간염바이러스항체 (+) 3. 간경변증 (+) 근거자료 6 개월마다 복부초음파검사및 혈청알파태아단백측정 암조기검진사업지원평가단권고안분과위원회

15 국가암조기검진사업 (NCSP): 간암 1 간암검진대상자확인방법 혈청 HBsAg 및 ALT 검사시행 B형간염바이러스표면항원 (+) 지피티 (ALT) 상승또는정상 B형간염바이러스표면항원 (-) 지피티 (ALT) 상승 B형간염바이러스표면항원 (-) 지피티 (ALT) 정상 국가간암검진사업등록 (+) C형간염바이러스항체 (-) 간암검진대상자에서제외 암조기검진사업지원평가단권고안분과위원회

16 국가암조기검진사업 (NCSP): 간암 검사결과에따른사후관리 (Recall Policies) 복부초음파검사 간결절 (-) < 20ng/ml 정기적검사반복 - 혈청알파태아단백검사 - 복부초음파검사 알파태아단백검사 간결절 (+) 20 ng/ml 1 간전문의상담후 2 추후확진검사시행 * 대한간암연구회 국립암센터간세포암종진료가이드라인참조

17 2003 간세포암종진료가이드라인 -2 대한간암연구회 - 국립암센터 L1 기본입원검사 L2 간염바이러스검사 말초혈액검사 혈청생화학검사 전해질검사 PT, aptt 혈액형검사 소변검사 대변검사 흉부촬영 심전도 선택검사 폐기능검사 (60세이상 ) VDRL, HIV 1 차 - HBsAg, HBsAb, HBcAb -Anti-HCV Ab 2 차 - HBsAg 양성인경우 HBeAg, HBeAb HBV DNA 정량검사 - Anti-HCV Ab 양성인경우 HCV RNA 정성검사 D1 간세포암종 1. 임상적진단 위험인자 (HBV 양성, HCV 양성, 간경변증등 ) 가있으면서, 혈청알파태아단백 > 400 ng/ml 이면, 아래의영상검사들중한가지이상에서간세포암종에합당한소견을보일때 혈청알파태아단백 < 400 ng/ml 이면, 아래의영상검사들중두가지이상에서간세포암종에합당한소견을보일때영상검사 : 나선식전산화단층촬영 (spiral CT), 역동적조영증강자기공명영상촬영 (dynamic MRI), 간동맥혈관조영술 (hepatic artery angiography) 2. 조직학적진단

19 < 국가조기검진사업간암검진결과서식 > 초음파검사 혈청알파태아단백검사 종합판정 검사결과 검진일년월일 병형 1. 정상 2. 이형결절 3. 간암의심 4. 간암 5. 양성종양 6. 기타 ( ) 병변부위 1. Ⅰ 2. Ⅱ 3. Ⅲ 4. Ⅳ 5. Ⅴ 6. Ⅵ 7. Ⅶ 8.Ⅷ 병변크기 1. 2 cm미만 2. 2 cm ~5 cm미만 3. 5 cm이상 간암형 1. 단발성결절형 2. 다발성결절형 3. 대종괴형 4. 미만형 문맥침범 1. 정상 2. 주문맥 3. 좌문맥 4. 우문맥 만성간질환 1. 정상 2. 만성간염 3. 간경변증 4. 지방간 기타이상ㅇ비장종대등추가이상소견을기술한다. ( ) 검진의사면허번호 : 검진의사명 : 검사일년월일 검사방법 1. 정성검사 2. 정량검사 세부검사방법 정성검사 : 1. RPHA 2. ICT 3. 기타 ( ) 정량검사 : 3. 효소면역측정법 (EIA) 4. RIA 5. CIA 6. 기타 ( ) 정성검사 1. 음성 (-) 2. 양성 (+) 정량검사검사결과 : ( ) 기준치 : ( ) 이하 단위 1. ng/ml 2. I.U./ml 자문의사면허번호 : 자문의사명 : 판정결과 1. 정상 2. 추적요망 3. 정밀검사필요 4. 암치료대상 5. 기타질환 ( ) 판정의사면허번호 : 판정의사 : ( 인 ) 출장검진여부 출장 내원

22 A Practical Approach of Surveillance and Recall for Patients with HBV+ve HCC Screening 선별 Surveillance 감시 and F/U Recurrence Cirrhosis Recall 소환 Follow-up Tx and F/U Diagnosis 추적 HBV Tx Surveillance

24 A Practical Approach of Surveillance and Recall Surveillance patient with risk USG + AFP q 6 mo patient with risk + suspect lesions (APS, r/o DN, unknown character lesions, poor view) USG/ alternative CT or MRI + AFP q 6 mo Recall and diagnosis patient with risk + nodule KLCSG-NCC + AASLD guideline

25 F/60 Case 국가암조기검진간초음파검사에서 1.5cm 간종괴발견후재검통보로정밀검사위해방문 Anti-HCV+, alcohol abuse+, IFN tx - r/o CH, Performance 0 AFP 7.2 ng/ml, PIVKAII 72 mau/ml CA U/ml

26 Arterial T1W dynamic Early portal T2 Bx? r/o CCC >> RFA? r/o WD HCC Op? Well Diff. HCC

27 Case F/48 HBsAg+, DNA > 10 8 copies/ml Liver cirrhosis, Child-Pugh class A 1.7cm S8 in the surveillance USG and AFP 10.5 ng/ml

28 Arterial phase T2W Portal phase USG and AFP q 6 mo r/o organizing r/o abscess Antiviral Tx q 3 mo SPIO HCC r/o CCC Follow-up? Over 3 yrs Bx? Bx? r/o DN Necrotizing and AFP granuloma RFA? Re-OP? RFA? Resection? 1.5 cm HCC grade II

29 Case F/62 HBsAg+, DNA < 2000 copies/ml Liver cirrhosis Child-Pugh B with multiple DN and RN, AFP 3.6 ng/ml surveillance q 3-4 mo with LC complication Tx over 2 yrs

30 New 2.1 cm lesion RFA?, LT?, TACE? AFP 59.3 ng/ml Bx? RFA?

32 Case M/65 효도 건강검진 (screening); liver mass, 3.0 cm Non-B, non-c, non-alcoholic AFP 3.7 ng/ml

33 Arterial Arterial Early portal Early portal Op; refused TACE Bx? Angio? f/u q 3-4 mo Op? l yr later Bx: HCC Bx: Eosinophilic abscess

34 Bruix J, Shermann M. Hepatology 2005 Surveillance and Recall Policies in Patients with higher risks of HCC Risk - HBV carrier male, age, cirrhosis, FHx, high DNA titer, ongoing hepatitis - Non-HBV cirrhosis Nodule + Large RN DN Surveillance Recall and diagnosis Follow-up After Tx interval tests interval tests interval tests 6-12 mo USG ±AFP?? 3-4 mo CT, MRI, Contrast US± Bx No consensus, Eminence-based

35 Prediction Models for Recurrence and Survival after Hepatectomy of Hepatocellular carcinoma SJ Park, BH Nam, SH Kim, SK Han, KW Lee, SY Cho, YK Kim, SA Lee, JI Choi, HB Kim, EK Hong, JW Park, CM Kim Center for Liver Cancer National Cancer Center, Korea SJ Park, et al. Kor J Hepatol 2008; 14 supp3: s54

36 Prognostic factors of HCC after hepatectomy Tumor factors : size, number, vascular invasion, differentiation, AFP Liver factors : hepatitis, cirrhosis, Child-Pugh score, ICG R15 Surgery factors : extent of resection, resection margin, transfusion operation complication Previous HCC staging systems: imperfect for predicting surgical patients. There is no prognosis prediction model for surgical patients of HCC SJ Park, et al. Kor J Hepatol 2008; 14 supp3: s54

37 Patients and Methods Apr Nov. 2006, 406 HCC patients with hepatectomy - Exclusion : 7 patients (6; age<20, 1; follow-up loss) 399 patients of HCC with age 20 Median follow-up : 36 months (12-68) until Dec Disease-free survival (DFS) & over-all survival (OS) : Kaplan-Meier Univariate and multivariate analysis Prognostic factors (p<0.1) : Cox Proportional Hazard Regression Model SJ Park, et al. Kor J Hepatol 2008; 14 supp3: s54

38 Multivariate Analysis for OS & DFS Overall Survival Disease-Free-Survival Variable p-value HR 95% CI p-value HR 95% CI AFP>15ng/ml Microvascular inv.(+) Major vessel inv.(+) Tumor No Complication ICG R15>10% Hepatitis B Hepatitis C R/M (+) SJ Park, et al. Kor J Hepatol 2008; 14 supp3: s54

39 Development of Prediction Model for DFS by Scoring System 1. Risk point assessment by relative risk Factors Risk point Hepatitis B 4 Hepatitis C 3 Hepatitis B+C 5 AFP>15ng/ml 2 Microvascular inv.(+) 4 2. Staging with sum of risk point Stage Range of Risk of recur point within 5 years I 0-3 <40% II % III % IV 12 >89% Major vessel inv.(+) 8 Tumor No.=2 1 Tumor No. 3 5 Resection Margin (+) 7 Complication 3 SJ Park, et al. Kor J Hepatol 2008; 14 supp3: s54

for DFS χ 2 = 58.97 AJCC stage χ 2 = 31.

40 Comparison of New Model for DFS with AJCC and Modified UICC Stages New Model for DFS χ 2 = AJCC stage χ 2 = n=42 n=170 n=132 n=55 Modified UICC χ 2 = However, follow-up interval? SJ Park, et al. Kor J Hepatol 2008; 14 supp3: s54

41 Summary Regular surveillance with USG and AFP should be necessary for patients at high risk of HCC Good physician with good radiology is essential The surveillance interval need not to be shortened for patients at higher risk However, patients with suspect HCC should be receiving enhanced follow-up

42 경청해주셔서감사합니다.

김범수

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