1. 경희대학교병원 간암 다학제증례집담회 Multidisciplinary case conference Liver Cancer Conference 소화기 센터 회의실 2013.6.28

2.  B-viral LC 와 DM 으로 한양대 병원 f/u 해옴  ‘12.10.10 Angina 로 심장내과 입원해 시행한 Abd US 상 suggestive of HCC at S5/7, Liver MR 상 HCC at S7 → TACE #1 (’12.10.23)  ‘12.12.13 CT : no recurrence of HCC  ’13.3.7 CT : no recurrence of HCC  ’13.6.4 MR : Viable tumor at the posterior aspect to the lipiodolized HCC at S7 → TACE #2 (’13.6.25)  토의 목적 : 향후 치료 방향 논의 (operability) History Case 1 12235403 김 O 열 M/49 DM/HTN/TBc/Hepatitis(+/-/-/+) : HBV carrier – Baraclude 0.5mg qd 복용 중 B-viral LC (Child A(5), MELD 5.68) with esophageal varix Op Hx (-) Alcohol Hx (-), Smoking Hx (+) : 과거흡연 (20py)

3. Underlying liver function and performance status CBC/DC WBC(mm 3 )6,010 Hb(g/dl)15.8 PLT(mm 3 )45,000 PT(sec)13.9 INR1.10 Performance status: Grade 0 Chemistry TB/DB(mg/dL)1.61/0.44 AST/ALT(IU/L)35/26 ALP/rGT(IU/L)54/39 Prot/Alb(g/dL)7.6/4.4 BUN/Cr(mg/dL)10/0.8 LC & Stage Child-PughA (5) MELD score7.16 Esophageal varices+ (CbF2LmRC-) Ascites- Encephalopathy- 12235403 김 O 열 M/49 Case 1 Tumor markers AFP (ng/mL)60.54 CEA (ng/mL) 2.74 PIVKA II (mAU/mL)15 CA 19-9 (U/mL) 4.43 Viral markers/ underlying liver disease HBV / HCV(+/-) HBeAg / HBeAb(-/+) Virus titer<20 IU/mL Antiviral TxBaraclude 0.5mg qd Alcohol-

4. ’12.10. ‘12.12. ’13.3. ‘13.6. TACE #1 (’12.10.23) TACE #1 (’12.10.23) Angina s/p PCI HCC at S7 Angina s/p PCI HCC at S7 10259334 조 O 복 F/57 B-viral LC DM B-viral LC DM CT : no recurrence Case 1 Tumor Stage and Clinical Course 12235403 김 O 열 M/49 MR : viable tumor at S7 12 년 10 월 12 년 12 월 13 년 3 월 13 년 6 월 AFP 162935.574160.54 PIVKA Ⅱ 52202315 PET-CT (2012.10.23) 1. C/W HCC at segment VII of liver 2. No abnormal hypermetabolic lesion suggesting metastasis *Liver-MRI (2013.6.4) Viable tumor at the posterior aspect to the lipiodolized HCC at S7. CT : no recurrence TACE #2 (’13.6.25) TACE #2 (’13.6.25)

5. Summary – 치료 방침 결정 12235403 김 O 열 M/49 Case 1 Current liver function Normal Well preserved (no risk of decompensation) Compensated (risk of decompensation) Decompensated Terminal state Extent of current tumor Localized (curative) Locally advanced (resectable) Locally advanced (unresectable) No < 4 Diffuse or multiple (> 3) Initial Tumor stage Date: 2012 년 10 월 Modified UICC ( 대한간암연구학회 ) T 2 N 0 M 0 Stage II JIS score 1 BCLC stage Very early / Early / Intermediate / Advanced / Terminal Current status Locally advanced with well preserved liver function Risk factors of recurrence / Tumor biology Extrahepatic metastasis N Tumor size > 5 cm, capsulation N Tumor number 1 Repeated TACE ( 1 회 / 기간 ) 1 Vascular or bile duct invasion N High uptake of PET Y High AFP or PIVKA II Y Not normalized AFP after curative Tx Y Histology (microvascular invasion) - Histology (satellite lesion, differentiation) - Poor control of underlying liver disease N ART score (Good Px 2.5) 1

6.  ’08 : Chronic hepatitis B, B-viral LC 진단받고 Entecavir 복용 시작  ‘10.1 : Autoimmune hepatitis 진단받고 치료  ‘12.1.6 CT : HCC at S6 → TACE #1 (‘12.1.13)  ‘12.9.20 CT & MR : Marginal recurrent HCC of lipiodolized HCC in S6 → Liver segmentectomy (‘13.1.3) → 수술 중 Diaphragm defect 발견 → 6 개월 후 수술적 치료 고려  ‘13.5.2 MR : s/p lumpectomy of segment 6 for HCC without recurred tumor  토의 목적 : 횡격막 결손에 대한 수술 등의 치료방향 논의 History Case 2 11860780 백 O 흠 F/63 DM/HTN/TBc/Hepatitis(+/+/-/+) : CHB B-viral LC (Child A(5), MELD -2.93) with esophageal varix Old CVA (+) : SAH with A-com aneurysm Op Hx (+) : GDC coiling & LP shunt (‘06), hysterectomy (‘94) Alcohol Hx (-), Smoking Hx (-)

7. Underlying liver function and performance status CBC/DC WBC(mm 3 )5,250 Hb(g/dl)12.6 PLT(mm 3 )142,000 PT(sec)12.9 INR0.98 Performance status: Grade 0 Chemistry TB/DB(mg/dL)0.43/- AST/ALT(IU/L)50/59 ALP/rGT(IU/L)100/- Prot/Alb(g/dL)8.4/4.4 BUN/Cr(mg/dL)-/- LC & Stage Child-PughA (5) MELD score-2.93 Esophageal varices+ (F1CbLiRC-) Ascites- Encephalopathy- 11860780 백 O 흠 F/63 Case 2 Tumor markers AFP (ng/mL)616.3 CEA (ng/mL) - PIVKA II (mAU/mL)52 CA19-9 - Viral markers/ underlying liver disease HBV / HCV(+/-) HBeAg / HBeAb(+/-) Virus titer22 IU/mL Antiviral TxBaraclude 0.5mg qd Alcohol-

8. ’08 ‘10.1. ’12.1. ‘13.1. Autoimmune hepatitis Autoimmune hepatitis 10259334 조 O 복 F/57 CHB c B-viral LC CHB c B-viral LC Case 2 Tumor Stage and Clinical Course 11860780 백 O 흠 F/63 TACE #1 (‘12.1.13) Liver MRI (2013.5.2) S/P lumpectomy of segment 6 for HCC without recurred tumor. No visible other arterial enhancing lesion in the liver. No change of an accessory spleen. Disappeared right pleural effusion. Chest-CT (2012.9.20) No evidence of metastasis. No change of Bochdaleck's hernia. CT : HCC at S6 CT & MR : Marginal recurrent HCC in S6 CT & MR : Marginal recurrent HCC in S6 12 년 1 월 12 년 3 월 12 년 6 월 12 년 9 월 12 년 12 월 13 년 5 월 AFP155.16.1527.7533.5937.52616.3 PIVKA II-32-6352 Liver segmentectomy (‘13.1.3) : diaphragm defect Liver segmentectomy (‘13.1.3) : diaphragm defect

9. Summary – 치료 방침 결정 11860780 백 O 흠 F/63 Case 2 Current liver function Normal Well preserved (no risk of decompensation) Compensated (risk of decompensation) Decompensated Terminal state Extent of current tumor Localized (curative) Locally advanced (resectable) Locally advanced (unresectable) No < 4 Diffuse or multiple (> 3) Initial Tumor stage Date: 2012 년 1 월 Modified UICC ( 대한간암연구학회 ) T 2 N 0 M 0 Stage II JIS score 1 BCLC Very early / Early / Intermediate / Advanced / Terminal Current status Localized advanced with well preserved liver function Risk factors of recurrence / Tumor biology Extrahepatic metastasis N Tumor size > 5 cm, capsulation N Tumor number 1 Repeated TACE ( 1 회 / 기간 ) 0 Vascular or bile duct invasion N High uptake of PET - High AFP or PIVKA II Y Not normalized AFP after curative Tx Y Histology (microvascular invasion) N Histology (satellite lesion, differentiation) N Poor control of underlying liver disease N ART score (Good Px 2.5) 0

10. History Case 3 11735816 정 O 자 F/69 DM/HTN/Tb/Hepatitis(-/+/-/+) : CHB B-viral LC with gastro-esophageal varix Old CVA (+) : cerebral infarction Op Hx (+) : appendectomy Alcohol Hx (-), Smoking Hx (-)  ’96. : Chronic hepatitis B  ’07.6. : B-viral LC  ‘12.2.8. CT : Suggestive a HCC in Rt lobe of liver (5.5 x 5.9 x 7.0 cm)  ‘12.4.25. CT : Slightly increased size of suggested a massive HCC in Rt lobe of liver (6.2 x 6.0 cm)  ‘13.5.31 MR : Suggestive of hepatic adenoma at S5-6 of the liver, r/o HCC. → Rt lobectomy of liver (‘13.6.17)  ‘13.6.24 CT : s/p Rt hepatic lobectomy and cholecystectomy  토의 목적 : 향후 치료 방향 논의

11. Underlying liver function and performance status CBC/DC WBC(mm 3 )6,070 Hb(g/dl)10.0 PLT(mm 3 )313,000 PT(sec)14.2 INR1.13 Performance status: Grade 0 Chemistry TB/DB(mg/dL)0.60/- AST/ALT(IU/L)23/35 ALP/rGT(IU/L)108/60 Prot/Alb(g/dL)5.5/2.8 BUN/Cr(mg/dL)10/0.7 LC & Stage Child-PughA (5) MELD score1.11 Esophageal varices Fundic varices + (CwF1LiRC-) - Ascites- Encephalopathy- 11735816 정 O 자 F/69 Case 3 Tumor markers AFP (ng/mL)5.27 CEA (ng/mL) - PIVKA II (mAU/mL)155 CA19-9 (U/mL) 3.58 Viral markers/ underlying liver disease HBV / HCV(+/-) HBeAg / HBeAb(-/+) Virus titer294 IU/mL Antiviral Tx- Alcohol-

12. Tumor Stage and Clinical Course ’96. ‘07.6. ‘12.2. ’13.5. Case 3 11735816 정 O 자 F/69 Liver-CT (2013.6.24) S/P right hepatic lobectomy and cholecystectomy AP shunt at left lobe of liver Postoperative air bubble, small amount of pelvic ascites,draining tube in left subhepatic space, and small bilateral pleural effusion and atelectaiss of BLL Calcified right renal artery aneurys with multiple infarction rather than acute pyelonehritis. A tiny left renal cyst PET (2013.6.7) Known hepatic mass with isometabolic activity in the right lobe Small hypermetabolic lesion at left adrenal gland, benign lesion, more likely --> REC) Radiologic correlation CHB CHB B-viral LC B-viral LC CT : suggestive HCC MR : suggestive hepatic adenoma, r/o HCC MR : suggestive hepatic adenoma, r/o HCC Rt loectomy (‘13.6.17) 07 년 6 월 10 년 1 월 13 년 5 월 13 년 6 월 AFP1.472.053.165.27 PIVKA II--289155

13. Summary – 치료 방침 결정 11735816 정 O 자 F/69 Case 3 Current liver function Normal Well preserved (no risk of decompensation) Compensated (risk of decompensation) Decompensated Terminal state Extent of current tumor Localized (curative) Locally advanced (resectable) Locally advanced (unresectable) No < 4 Diffuse or multiple (> 3) Initial Tumor stage Date: 2012 년 2 월 Modified UICC ( 대한간암연구학회 ) T 2 N 0 M 0 Stage II JIS score 1 BCLC Very early / Early / Intermediate / Advanced / Terminal Current status Resected with well preserved liver function Risk factors of recurrence / Tumor biology Extrahepatic metastasis N Tumor size > 5 cm, capsulation Y Tumor number 1 Repeated TACE ( 1 회 / 기간 ) - Vascular or bile duct invasion Y High uptake of PET N High AFP or PIVKA II Y Not normalized AFP after curative Tx N Histology (microvascular invasion) Y Histology (satellite lesion, differentiation) - Poor control of underlying liver disease N ART score (Good Px 2.5) -

15. Hepatocellular carcinoma, (trabecular type), unifocal 1) Tumor size : 8.3x7.7 cm 2) Tumor gross type : expanding nodular 3) Edmondson-Steiner grade 2/4 4) Tumor extent Solitary tumor nodules confined to right lobe of the liver Hepatic capsular penetration : not identified Vascular invasion : present Involvement of branches of portal vein Tumor thrombi in small vessels 5) The parenchymal, distal bile duct, and vascular margins are free of tumor The tumor is 0.8 cm. from the parenchymal resection margin The tumor is 1.0 cm. from the distal bile duct margin 6) Lymph node status: No metastasis in 1 regional lymph node ( 0/1 ) 7) pTN Stage : pT2N0 8) Additional pathologic findings a. Fibrosis stage (by Ishak et al.) Marked bridging with occasional nodules (incomplete cirrhosis) (5) b. Steatosis : present c. Dysplastic nodule : not identified

18.  ’92. : Chronic hepatitis B  ’11.6. MR : Multiple nodular HCCs in left lobe of liver with PVT → TACE #1 (‘11.6.17)  ’11.6. CT : incompletely lipiodolized PVT, infiltrative HCC → TACE #2 (‘11.7.25)  ‘11.9. CT : recurrent, infiltrative HCC with PVT → TACE #3 (‘11.9.27)  ’11.11. MR : viable tumor at postero-inferior margin with PVT → Tomotherapy (‘11.12.14~’12.1.20)  ‘13.6. MR : suggestive of diffuse infiltrating HCC at left lobe  토의 목적 : 향후 치료 방침 논의 (TACE or operation) History Case 4 12205109 김 O 수 M/47 DM/HTN/Tbc/Hepatitis(-/-/-/+) : CHB B-viral LC(Child A(6), MELD 0.57) Op Hx (-) Alcohol Hx (+) : 과거 음주, Smoking Hx (+) : 과거 흡연, 20py

19. Underlying liver function and performance status CBC/DC WBC(mm 3 )6,220 Hb(g/dl)15.7 PLT(mm 3 )152,000 PT(sec)13.5 INR1.03 Performance status: Grade 0 Chemistry TB/DB(mg/dL)0.37/0.12 AST/ALT(IU/L)37/40 ALP/rGT(IU/L)91/155 Prot/Alb(g/dL)7.6/4.0 BUN/Cr(mg/dL)-/- LC & Stage Child-PughA(6) MELD score0.67 Esophageal varicesunchecked Ascites- Encephalopathy- 12205109 김 O 수 M/47 Case 4 Tumor markers AFP (ng/mL)2,240 CEA (ng/mL) - PIVKA II (mAU/mL)48 CA19-9 (U/mL) - Viral markers/ underlying liver disease HBV / HCV(+/-) HBeAg / HBeAb(+/+) Virus titer<20 Antiviral TxBaraclude 0.5mg qd Alcohol - ( 과거 음주 )

20. ‘92 ‘11.6~9. ‘11.11. ‘13.6. 6/14 MR : Multiple nodular HCCs with PVT 6/27 CT : infiltrative HCC with PVT 9/5 CT : recurrent, infiltrative HCC with PVT 6/14 MR : Multiple nodular HCCs with PVT 6/27 CT : infiltrative HCC with PVT 9/5 CT : recurrent, infiltrative HCC with PVT 10259334 조 O 복 F/57 CHB Case 4 Tumor Stage and Clinical Course 12205109 김 O 수 M/47 Liver-MR (2013.6.18) Post-Tomotherapy follow up. Suggestive of diffuse infiltrating HCC rather than radiation hepatitis at left lobe. No interval change of thrombosis within the umbilical segment of the left portal vein. Suggestive of several small DNs at right lobe of the liver, no interval change. Several hepatic cysts at right lobe of the liver. PET-CT (2013.6.19) New two hypermetabolic lesions at left lateral segment of liver, suggestive of recurred HCCs R/O post-radiation hepatitis MR : viable tumor with PVT MR : diffuse infiltrating HCC Tomotherapy (‘11.12.14~’12.1.20) TACE #1 (‘11.6.17) #2 (‘11.7.25) #3 (‘11.9.27) 11 년 6 월 11 년 9 월 12 년 2 월 12 년 10 월 13 년 2 월 13 년 6 월 AFP3645011942408.6597.9896.52240 PIVKA II-3725747948

21. Summary – 치료 방침 결정 12205109 김 O 수 M/47 Case 4 Current liver function Normal Well preserved (no risk of decompensation) Compensated (risk of decompensation) Decompensated Terminal state Extent of current tumor Localized (curative) Locally advanced (resectable) Locally advanced (unresectable) No < 4 Diffuse or multiple (> 3) Initial Tumor stage Date : 2011 년 6 월 Modified UICC ( 대한간암연구학회 ) T 4 N 0 M 0 Stage IV JIS score 3 BCLC Very early / Early / Intermediate / Advanced / Termin Current status Diffuse with well preserved liver function Risk factors of recurrence / Tumor biology Extrahepatic metastasis N Tumor size > 5 cm, capsulation N Tumor number 1 Repeated TACE ( 1 회 / 기간 ) 2 Vascular or bile duct invasion - High uptake of PET Y High AFP or PIVKA II Y Not normalized AFP after curative Tx Y Histology (microvascular invasion) - Histology (satellite lesion, differentiation) - Poor control of underlying liver disease N ART score 1

22.  DM, Alcoholic & B-viral LC Hx (+), HCC s/p RFA state (+)  ’11.11. CT : Newly visible two omental masses(3cm, 1.7cm) in the left perihepatic space → Laparoscopic tumorectomy of omental masses (’11.12.23)  ’12.1.12~’12.3.13 : Sorafenib  ’13.6.21 MR : New HCC at left perihepatic space  토의 목적 : 향후 치료 방침 논의 History Case 5 12113057 김 O 수 M/63 DM (+), CHB (+) Alcoholic & B-viral LC : uncheckable grade Op Hx (+) : laparoscopic tumorectomy (‘11.12.23) Alcohol, Smoking : uncheckable

23. Underlying liver function and performance status CBC/DC WBC(mm 3 )5,610 Hb(g/dl)17.1 PLT(mm 3 )80,000 PT(sec)13.7 INR1.06 Performance status: Grade 0 Chemistry TB/DB(mg/dL)0.78/- AST/ALT(IU/L)32/19 ALP/rGT(IU/L)65/236 Prot/Alb(g/dL)7.5/4.3 BUN/Cr(mg/dL)15/0.6 LC & Stage Child-Pughuncheckable MELD score0.68 Esophageal varices+ (CbF1~2LmERC-) Ascitesuncheckable Encephalopathyuncheckable 12113057 김 O 수 M/63 Case 5 Tumor markers AFP (ng/mL)704.5 CEA (ng/mL) - PIVKA II (mAU/mL)16 CA19-9 (U/mL) - Viral markers/ underlying liver disease HBV / HCV(+/-) HBeAg / HBeAb(-/+) Virus titer<20 (‘11.12.19) Antiviral Tx- Alcohol+

24. ‘11.11. ‘12.1~3. ‘13.6. CT : two omental masses in Lt perihepatic space 10259334 조 O 복 F/57 DM Alcoholic & B-viral LC HCC s/p RFA DM Alcoholic & B-viral LC HCC s/p RFA Case 5 Tumor Stage and Clinical Course 12113057 김 O 수 M/63 Liver-MR (2013.6.21) New HCC at left perihepatic space. Post RFA lesion at the liver segment 7/8. with no evidence of viable or recurrent tumor. PET-CT (2011.12.20) Two mild hypermetabolic omental mass in left perihepatic space ; R/O Metastatic lesions. Laparoscopic tumorectomy (‘11.12.23) 11 년 11 월 12 년 3 월 12 년 10 월 13 년 1 월 13 년 3 월 13 년 6 월 AFP36.45139.6253.8291.8225.7704.5 PIVKA II8233271916 Sorafenib MR : new HCC at Lt perihepatuic space

25. Diagnosis : Omentum, excision: Hepatocellular carcinoma, metastatic 1) size: 3x2.5x1.8 cm 2) Edmondson-Steiner grade III 3) no tumor identified at resection margins (safety margin: 0.2 cm) Omentum, excision: Hepatocellular carcinoma, metastatic 1) size: 0.9x0.5 cm 2) Edmondson-Steiner grade III 3) no tumor identified at resection margins (safety margin: 0.1 cm)