1. Management of Hepatocellular carcinoma
-2010 AASLD guideline-
Kyung Hee University
Byung-Ho Kim

2. Liver Cancer in the world
Bosch F, et al. Gastroenterology 2004;127:s5.

3. Cancer incidence in Korea, 2007
Stomach, 16.0
Thyorid 13.1
Colon, 12.7
Lung
11.0
Liver
9.2
한국에서 암발생 순서를 보면, 간암은 위암 (16%), 갑상선암, 대장암, 폐암에 이어 5번째로 많은 암입니다.

4. Cancer incidence according to gender
Male Female
Stomach Thyroid
Lung Breast
Colon Stomach
Liver Colon
Prostate Lung
Liver

5. Etiology of HCC in Korea
1) HBV
2) HCV
3) Alcohol

6. 5 year survival rate of various cancer in Korea
Thyroid Breast Prostate Cervix
Stomach Colon
Lung Liver GB Pancreas

7. Case 1) M/51, Liver cirrhosis-HBV
MR – axial view MR – coronal image

8. Risk factor(HBV, HCV, LC)
Diagnosis of HCC
Clinical Dx.
Risk factor(HBV, HCV, LC)
AFP <200 ng/mL
CT, MRI, HA* (2)
AFP ≥200 ng/mL
CT, MRI (1)
Liver cirrhosis ≥ 2 cm
Pathological Dx
No risk factor
Atypical case
Obscure image
*HA, hepatic angiograhy

9. Diagnostic algorithm for suspected HCC (2010 AASLD guideline)

10. TNM classification 종양수 1개 크기 < 2cm 혈관침범
* adopted from LCSGJ: Ueno S, et al. Hepatol Res 2002;24:395

11. BCLC staging of HCC Stage 0 PST 0, CP-A Stage A Stage B Stage C
Child-Pugh A-B
Stage D
PST >2, CP-C
The usefulness of portal pressure measurement to predict the outcome of patients and define optimal candidates for resection has been validated in Japan. Thus, resection should remain the first option
for patients who have the optimal profile. A cohort study of RFA demonstrated that complete ablation of lesions smaller than 2 cm is possible in more than 90% of cases, with a local recurrence rate of less than 1%. These data should be confirmed by other groups before positioning ablation as the first-line approach for very early HCC.
The recommendations regarding patient selection and method of TACE are unchanged. Radioembolization, i.e., the intra-arterial injection of yttrium-90 bound to glass beads or to resin, has been shown to induce tumor necrosis, but there are no data comparing its efficacy to TACE or to sorafenib for those with portal vein invasion. However, for patients who have either failed TACE or who present with more advanced HCC, new data indicates the efficacy of sorafenib (a multikinase inhibitor with activity against Raf-1, B-Raf, vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor, c-Kit receptors, among other kinases) in prolonging life. Sorafenib induces a clinically relevant improvement in time to progression and in survival. The most frequent adverse events were diarrhea (sorafenib vs placebo: 11% vs 2%) and hand–foot skin reaction (sorafenib vs placebo: 8% vs <1%), fatigue, and weight loss. Sorafenib is now considered first-line treatment in patients with HCC who can no longer be treated with potentially more effective therapies.

12. Laparoscopic hepatectomy

13. Surgical resection of HCC
The optimal candidate: 20% of patients with HCC
Single mass
Preserved liver function: Child-Pugh class A
Advantages
Cure possible
Expect long-term survival
Disadvantages
Operative mortality < 3%
High recurrence rate >70% at 5 years
Persistence of underlying liver disease

14. Liver transplantation
The optimal candidates
Milan criteria: single < 5 cm, up to 3 nodules < 3 cm
UCSF criteria: single < 7 cm, 3 nodules < 5 cm, 5 nodules < 3 cm
Advantage
Simultaneously cure the tumor and the underlying liver cirrhosis
Disadvantage
Postoperative mortality: 10%
High cost
Donor shortage
Donor mortality in living donor LT: < 1%

15. AASLD guideline on LT
LT is an effective option for patients with HCC corresponding to the Milan criteria (level II). Living donor transplantation can be offered for HCC if the waiting time is expected to be so long that there is a high risk of tumor progression leading to exclusion from the waiting list (level II).
No recommendation can be made regarding expanding the listing criteria beyond the standard Milan Criteria (level III).
Preoperative therapy can be considered if the waiting list exceeds 6 months (level II).
The development of living donation has further stimulated the discussion about expansion of the tumor
burden limits for HCC patients. Since transplantation can be done with almost no delay and staging
would be recent, several programs have proposed that living donation might be a valid option for those
patients whose tumor stage does not allow listing for cadaveric liver transplantation. Cadaveric livers would
then be allocated to patients with the best potential outcome (70% at 5 years), and living donation livers
would benefit patients with a lower expectancy, around 50% at 5 years. There are no data to support utilizing such expanded criteria.188

16. Case 2) F/65, LC-HBV
CT – arterial phase CT – delayed phase

17. Sono-guided radiofrequency ablation (RFA)

18. RFA & Follow-up CT Sono-RFA Post–RFA 2.5 years later
좌측 사진을 초음파를 보면서 탐침자를 삽입하여 고주파를 가하는 사진이고,
중간 사진은 RFA를 한 직후에 촬영한 CT 사진으로 치료가 잘 되었음를 보여주고 있다.
우측 사진은 2년 반이 지나서 촬영한 CT로 재발이 없음을 보여주고 있다.
Sono-RFA Post–RFA years later

19. Case 3) M/65, Russian, LC-HCV
Yakutsk
CT-arterial CT-delayed

20. Liver MRI (magnetic resonance imaging)

21. Trans-Arterial Chemo-EmbolizationPV HA

22. TACE

23. TACE The optimal candidates Advantages Limitations
patients with inoperable HCC
preserved liver function: Child-Pugh score A & B
Advantages
Less systemic side effects
Applicable to even multiple tumors
Limitations
Peripheral portion of tumor , hypovascular tumor
Marginal effect on survival
Portal vein thrombosis, total bilirubin > 3 mg/dL

24. AASLD guideline for advanced HCC
TACE is recommended as first line non-curative therapy for non-surgical patients with large/multifocal HCC who do not have vascular invasion or extrahepatic spread (level I).
Sorafenib is recommended as first line option in patients who can not benefit from resection, transplantation, ablation or TACE, and still have preserved liver function (level I).
Tamoxifen, anti-androgens, octreotide or hepatic artery ligation/embolization are not recommended (level I).

25. Radioembolization with Yttrium90-labeled glass beads has been shown to induce extensive tumour necrosis with acceptable safety profile. However, there no studies demonstrating an impact on survival and hence, its value in the clinical setting has not been established and cannot be recommended as standard therapy for advanced HCC outside clinical trials (level II).
Systemic or selective intra-arterial chemotherapy is not recommended and should not be used as standard of care (level II).

26. Case 4) M/50 LC-HBV Large HCC, Stage III  TACE 6 times 2008.5.26.
수술은 IVC에 접하고 있어 어려울 것으로 판단함.

27. Tomotherapy, CT-guided IMRT (Intensity Modulated Radiation Therapy)
The optimal candidates
patients with preserved liver function, but other treatment modalities are not applicable.
Advantage
save surrounding normal tissue
simultaneous targeting of multiple tumor lesions
less side effects
Disadvantage
expensive

28. Total dose: 5,000cGy/20Fx Daily dose: 250cGy Duration: 4 weeks
본 환자에 적용한 tomotherapy로 적색 부위가 방사선 조사 부위.
오른쪽 아래의 그래프는 각 부위의 방사선 조사량 표로, 간암 근접해있는 척추나 콩팥 조직에 방사선량을 최소화하고 간암조직에만 방사선을 집중.
Liver
Spinal Cord
Total dose: 5,000cGy/20Fx
Daily dose: 250cGy
Duration: 4 weeks
Rt. kidney

29. Follow-up after tomotherapyCT MR MR

30. Response to tomotherapy in Kyung Hee University
Objective response = CR + PR = 52.9%
본원 tomotherapy 치료 결과, 약 반 정도에서 효과를 보이며(위 그림), 중앙생존기간도 2년 정도로 기대 이상이었음.
Kaplan-Meier survival curve

31. Summary - I HCC is prevalent and 5th most common cancer in Korea.
Surgical resection is primary curative therapy in patients with single HCC and preserved liver function.
Liver transplantation is also curative therapy in patients with HCC within Milan criteria.
Radiofrequency ablation is effective and curative treatment in patients with small HCC, less than 3 in number.

32. Summary - II
Transarterial chemoembolization is primary therapy in patients with inoperable HCC and compensated liver function.
Tomotherapy may have a therapeutic role in HCC patients to whom other treatment modalities are not applicable but whose liver function is compensated.
A multidisciplinary team approach seems essential to further improve prognosis in HCC patients.