1. The 44th Congress of the Korean Association of HBP Surgery
Staged Partial Hepatectomy Versus Transarterial Chemoembolization for the Treatment of Spontaneous Hepatocellular Carcinoma Rupture: A Multicenter Analysis in Korea.
Hyung Soon Lee, MD1, Gi Hong Choi, MD1, Jin Sub Choi MD1, Kwang-Hyub Han, MD2, Sang Hoon Ahn, MD2, Do Young Kim, MD2, Jun Yong Park, MD2, Seung Up Kim, MD2, Sung Hoon Kim, MD3, Yoon Dong Sup, MD4, Jae Keun Kim, MD4, Jong Won Choi, MD5 , Soon Sun Kim, MD6, Hana Park, MD7
1Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. 2Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
3Department of Surgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
4Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
5Department of Internal Medicine, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea.
6Department of Internal Medicine, Ajou University Medical Center, Ajou University School of Medicine, Suwon, Korea.
7Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.

2. AJCC cancer staging manual. 7th ed. Chicago: Springer; 2009.
Background
Spontaneous rupture of hepatocellular carcinoma (HCC)
- Considered as T4 stage (AJCC 7th)
- Evokes risk of peritoneal metastasis
AJCC cancer staging manual. 7th ed. Chicago: Springer; 2009.

3. Background
An Analysis of 1160 Cases From a Nationwide Survey in Japan
Spontaneous tumor rupture had an additional negative impact on the baseline tumor status.
This impact corresponded to an additional 0.5 to 2.0 TNM stages.
Aoki T et al. Ann Surg. 2014 Mar;259(3):

4. Chan AC et al. Surgery. 2015 Aug 18
Background
Spontaneous tumor rupture affects the outcome of partial hepatectomy for T1T2 disease or tumor ≤ 10 cm only.
Assigning all resectable ruptured tumors to T4 may overestimate the severity of disease.
Chan AC et al. Surgery. 2015 Aug 18

5. Lee HS et al. World J Surg. 2014 Aug;38(8):2070-8
Background
Unmatched
After propensity score-matching.
Spontaneously ruptured HCC with staged hepatectomy shows comparable long-term survival and recurrence pattern versus non-ruptured HCC, with similar tumor characteristics and liver functional status.
Lee HS et al. World J Surg Aug;38(8):2070-8

6. Background
Although recent studies have shown favorable long-term outcomes of staged partial hepatectomy in well-selected cases, the optimal treatment modality in patients with ruptured HCC remains unclear.
Resection and TACE mainly performed treatment modality in patients with ruptured HCC.
However, very few studies had specifically investigated the survival benefit between staged hepatectomy and TACE for patients with ruptured HCC.

7. Purpose
Thus, we aimed to compare the long-term outcomes of treatment with staged hepatectomy or with TACE for patients with ruptured HCC.
To identify prognostic factors for patients with ruptured HCC to select optimal candidates for staged partial hepatectomy.

8. Methods Retrospectively review with medical records
Duration : from 2000 to 2014
Subject
- Age : 18 ~ 80
- Newly diagnosed HCC as ruptured tumor
Multicenter study involving 6 hospitals
- Severance Hospital
- Gangnam Severance Hospital
- Wonju Severance Christian Hospital
- National Health Insurance Corporation Ilsan Hospital
- Ajou University Medical Center
- CHA Bundang Medical Center

9. Results

10. Patients Number according to the Treatment Modality
Center
Total Number
Surgery *
TACE
Supportive care
Chemotherapy
Radiotherapy
Severance Hospital
60 (34.9%) 27 31 2
Gangnam Severance Hospital
25 (14.5%) 6 11 3
Wonju Severance Christian Hospital
32 (18.6%) 7 17 1
CHA Medical Center
15 (8.7%) 12
National Health Insurance Corporation Ilsan Hospital
20 (11.6%) 8 10
Ajou University Medical Center 5
172 (100%)
49 (28.5%)
90 (52.3%)
23 (13.4%)
5 (2.9%)
* Staged partial hepatectomy + Bleeder ligation

11. Scheme of Patients Selection
Spontaneous rupture of HCC (n=172)
Child-Pugh A (n=117, 71.3%)
Surgery (n=49)
Staged hepatectomy (n=44)
Bleeder ligation (n=5)
TACE (n=61)
*Conservative (n=7)
Child-Pugh B (n=37, 22.6%)
TACE (n=20)
*Conservative (n=17)
Child-Pugh C (n=10, 6.1%)
TACE (n=4)
*Conservative (n=6)
Concomitant extrahepatic metastasis (n=8)
*Conservative
: Supportive care, Radiotherapy, Chemotherapy
Duration :
Median follow-up time: 5 months (range, 0-162)

12. Staged Hepatectomy vs TACE
Patient characteristics at diagnosis of tumor rupture
Staged hepatectomy (n=44)
TACE (n=61)
P value
Age (yrs)
51.5 ( )
61 ( )
0.009
Sex (M : F)
34:10
52:9
0.295
HBV (+) *
36 (81.8%)
42 (68.9%)
0.495
Shock on presentation*
13 (29.5%)
24 (39.3%)
0.300
Portal vein thrombosis*
4 (9.1%)
12 (19.7%)
0.137
Tumor size (cm)
6.7 ( )
8.4 ( )
0.012
Multiple tumor*
5 (11.4%)
26 (42.6%)
0.001
Pre-treatment transfusion*
21 (47.7%)
37 (60.7%)
0.189
Pre-treatment transfusion >1200 (mL) *
12 (27.3%)
0.199
AFP (ng/mL)
144.5 ( )
62 ( )
0.082
DCP (mAU/mL)
806.5 ( )
2000 ( )
0.249
Hemoglobin (g/dL)
11.6 ( )
10.7 ( )
0.045
Platelet (103/µL)
184k (69k-467k)
165k (65k-454k)
0.138
Creatinine (mg/dL)
0.8 ( )
1.0( )
0.419
AST (IU/L)
52 (12-386)
67 (20-466)
0.061
ALT (IU/L)
45.5 (7-136)
43 ( )
0.084
Total bilirubin (mg/dL)
0.75 ( )
0.9 ( )
0.006
INR
1.06 ( )
1.13 ( )
0.078
*The data are presented as numbers and percentages.

13. Overall Survival according to the Main Treatment Modality
Staged hepatectomy vs TACE

14. Type of Resection Rt. hemihepatectomy 11 (25.0%) Lt. hemihepatectomy
Number (%)
Rt. hemihepatectomy
11 (25.0%)
Lt. hemihepatectomy
7 (15.9%)
Lt. extended hemihepatectomy
2 (4.5%)
Central bisectionectomy
Lt. lateral sectionectomy
6 (13.6%)
Anterior sectionectomy
1 (2.3%)
Posterior sectionectomy
Segmentectomy
8 (18.2%)
Wedge resection
44 (100%)

15. Complication after Staged Hepatectomy
Complication analysis by Clavien-Dindo classification†
Complication
Grade
Number (%)
Wound problem I
4 (3.8%)
Pleural effusion
5 (4.8%)
Ileus II
2 (1.9%)
Fluid colllection *
Acute renal failure #
1 (1.0%)
17 (16.2%)
* Antibiotics change due to fever
# Managed conservatively
† Dindo D. et al. Ann Surg 2004;240:205–213.

16. Recurrence Pattern after Staged Hepatectomy
Recurrence after staged hepatectomy (31/44, 70.5%)
Number of patients 16
(51.6%)
7 (22.6%)
2 (6.5%)
4 (12.9%)
1 (3.2%)
1 (3.2%)

17. Univariate Cox Regression Analysis of Prognostic Factor
Variable
Categories
Disease-free Survival
Hazard Ratio
95% Confidence Interval
P value
Age
1-year increase
1.940
0.164
Gender
Female vs Male
0.008
0.929
HBsAg positivity
No vs Yes
1.095
0.295
Shock on presentation
0.140
0.708
Portal vein thrombosis
13.333
<0.001
Type of treatment
Staged hepatectomy vs TACE
26.205
Pre-treatment transfusion >1200 mL
5.005
0.025
Hemoglobin , g/dL
1.271
0.260
Creatinine , mg/dL
2.109
0.146
Albumin, g/dL
0.776
0.378
AST, IU/L
2.225
0.136
ALT, IU/L
0.697
0.404
Platelet, mm3
0.006
0.940
Total bilirubin, mg/dL
3.598
0.058
INR
0.173
0.678
AFP, IU/mL
5.162
0.023
DCP, mAU/mL
0.415
0.519
Tumor size > 5cm
9.154
0.002
Multiple tumor
Solitary vs Multiple
8.633
0.003

18. Multivariate Cox Regression Analysis of Prognostic Factor
Variable
Categories
Disease-free Survival
Hazard Ratio
95% Confidence
Interval
P value
Type of treatment
Staged hepatectomy vs TACE
17.027
<0.001
Pre-treatment transfusion >1200 mL
No vs Yes
4.135
0.042
Portal vein thrombosis
10.485
0.001
Tumor size > 5cm
4.183
0.041

19. Comparison of Overall Survival between Staged Hepatectomy Group and TACE Group
by using propensity score match

20. Comparison of Demographics in the Propensity Score Model
Variable
Categories
Before Matching
After Matching
Staged hepatectomy (n = 44)
TACE
(n = 85)
P value
Staged hepatectomy (n = 16)
(n = 16)
Age (yrs)
53.43±12.70
59.63±12.07
0.0076
57.38±13.64
57.38±14.66
>.9999
Hemoglobin (g/dL)
11.01±2.16
10.55±2.27
0.2616
11.44±1.97
11.35±1.73
0.9023
Tumor size (cm)
6.98±3.23
9.25±4.51
0.0014
7.82±3.42
7.83±2.63
0.9942
Multiple Tumor *
5(11.4%)
38(44.7%)
0.0001
2(12.5%)
Child-Pugh grade * A
44(100%)
61(71.8%)
<.0001
16(100%) NA B
0(0%)
20(23.5%) C
4(4.7%)
*The data are presented as numbers and percentages.

21. Staged Hepatectomy vs TACE Overall survival (after match)

22. Conclusion
Our study indicates that staged partial hepatectomy may offer better long-term survival than TACE for HCC with recent tumor rupture.
Multivariate analysis showed that type of treatment, pre-treatment transfusion above 1200mL, presence of portal vein thrombosis, and tumor size above 5cm were associated with poor prognosis of patients.
Further clinical studies are required in the form of prospective randomized trials with adequate sample sizes and prolonged follow up.

23. Thank you for your attention