1. Experience of ALPPS procedure in treating hepatocellular carcinoma
謝沛民 謝焜州 陳耀森
高雄義大醫院外科部一般外科
Pei-min Hsieh, Kun-chou Hsieh, Yaw-sen Chen
Division of General Surgery, Department of Surgery, E-Da Hospital, Kaohsiung

2. Introduction
ALPPS:
Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy

3. Combines liver partition with portal vein ligation (1st stage operation) followed by a 2nd operation to remove the deportalized, diseased part of the liver

4. What is allps

5. History of ALPPS In 2007, Dr. Hans Schlitt from Regensburg
Extended right hepatectomy for Klastin tumor
Insufficient FLR (future liver remnant) during operation
Divided the liver parenchyma along the falciform ligament to perform left hepatico-jejunostomy
PVL immediately

6. Prevent post-hepatectomy hepatic failure
Advantages of ALPPS
Prevent post-hepatectomy hepatic failure
Extend possibility of R0 hepatectomy for malignancy
Rationale:
Regeneration power of hepatocyte
Portal vein ligation induce hypertrophy of contralateral side liver lobe

7. Case Report

8. 53 y/o male
HBV+
HCC diagnosed 2015/04
CT scan: infiltrating tumor at S8 with right anterior PV thrombosis
s/p TACE, R/T and sorafenib
AFP down from 1097 to 15

9. 11/25 first stage
right lobe: 1130 cm3, left: 310 cm3 , body weight 74 kg
310/1440 = 21.3%
310/74000 = 0.42%
ICG 24.8% Hb: 15.4, Plt:105,000 Bil-T:1.01, Alb:4.0

12. 12/03 second stage
right lobe:936cm3, left: 540cm3 (0.729%)
lab: Hb = PLT = 131,000. T-bil = 1.35, Alb=3.4
Left lobe volume increasing rate:
( )/310 = 74.5%

13. Material and Method

14. Between 2015 June to 2016 May,
We choose six HCC patients undergoing ALPPS procedure.
The inclusion criteria included
Estimated FLR less than 35%
Child A liver function
ICG test < 25
Platelet number > /ml

15. 1st Hepatectomy Transection liver parenchyma with CUSA
Hanging or anterior approach
Right portal vein was ligated
Right and Middle (option) hepatic vein were preserved
Right hepatic artery and right hepatic duct were identified and preserved
Anti-adhesive material (Sepafilm) was placed over transection surface

16. F/U liver function post-op day 1 and 5
Interval period
F/U liver function post-op day 1 and 5
F/U liver CT and volumetry on the day before 2nd operation (post-op day 6 or 7)
If total bilirubin > 2 or FLR / Pre-op Total volume < 40%, the 2nd operation should be delayed

17. 2nd operation Performed 7 or 8 days after 1st hepatectomy
Transection of Right portal pedicle
Transection of right and middle hepatic vein
Removal of diseased liver

18. Results

19. Patient Profile - 1 number Age Sex Hepatitis Child score ICG PLT (K)
Estimate FLR
FLR/BW 1 72 M B A
7.9
134
34% (379/1109)
0.52% 2 65 N
15.2
171
34% (405 /1179)
0.56% 3 54 24
105
27% (310/1141)
0.43% 4 61
4.6
177
30% (346/1157) 5 44
21.1
277
23.6% (325/1377)
0.47% 6 57 C 17
145
24.8% (315/1268)
0.45%

20. Patient Profile - 2 number Major vascular invasion AFP ng/ml
Pre-op management 1 Y
(Right PV) 2
TACE x II
(Middle HV)
4334
RTO + TACE x III 3 15
RTO + TACE x II + N 4
5.7
TACE x III, PEI 5
(Right HV)
325 N 6
142
TACE x I

21. Result 55% 61% 74% 45% 77% 67% number 1st Operative time (m)
1st OP Blood loss
2nd stage op interval (d)
FLR
FLR increasing ratio
FLR ratio
Bil T before 2nd operation
MELD Score 1
317
464 7
586
55%
( /379)
52%
1.53 9 2
345
700
653
61%
( /405)
1.47 8 3
275
400
540
74%
( /310)
48%
1.35 15 4
268
150
500
45%
( /346)
43%
0.92 6 5
247
300
615
77%
( /325)
1.56 16
347
270
595
67%
( /315)
47%
1.37

22. Result number morbidity recurrence Follow period (m) AFP (ng/ml) 1 N15
1.6 2
1.7 3
Y, Grade 1
(pleural effusion) 13
3.3 4
Y, Grade 3 P
(post-op 11 m) 14
3.01 5 9
4.5 6
(bile leakage) 10
1.5

23. Discussion

24. R0 resection for malignancy
Post-hepatectomy liver failure still be the problem
Extended functional remain liver volume  extended possibility of R0 resection
Portal vein embolization, portal vein ligation
Redistribute portal venous blood flow
Compensatory hypertrophy

25. Portal vein embolization failure
Progression of disease(10%)
Inadequate hypertrophy(5%)
A. Abulkhir,, Ann. Surg. 247 (2008) 49e57

26. Failure of PVE or PVL for hypertrophy
Regeneration power of hepatocyte
Cirrhosis
Chemotherapy
Intra-liver communication
Recanalization of embolization

27. Why do ALPPS be superior ?
Faster and Larger
Prevent collaterals and communications completely
Parenchymal transection trigger liver regeneration
K.J. Riehle, Hepatol. 26 (2011)
K. Abshagen. Langenbecks Arch. Surg. 397 (2012)

28. Complete 2nd surgery: ALPPS 86% : PVE 66%
Hypertrophy: ALPPS 77% : PVO 34%
E. Schadde. World J. Surg. 38 (2014)

29. Outcomes

30. Mortality and morbidity
Long term follow up

31. Mortality and morbidity
90-days mortality: 12 %
77% mortality were due to post-hepatectomy liver failure
Bilirubin level between the two steps as a predictor
Age more than 70 years
Marcello Donati. Future Oncol. 2015,11:2255-8

32. Mortality and morbidity
Higher morbidity rates than conventional hepatectomy
Overall Major morbidity(> grade IIIB) 28%
Hilar cholangiocarcinoma or gall bladder cancer with biliary reconstruction
E. Schadde, Ann. Surg. 260 (2014)

33. Long term follow up
Disease-free survival (DFS) at a median of 180 days :73%~95%
1 and 2-year DFS for CRLM : 59%
liver-specific recurrence rate of 86% at 15months
K.A. Bertens Intl J Surg 13 (2015)

34. Increased proliferative activity of HCC ?

35. Liver regeneration vs. Carcinogenesis
Same stimulators
Same pathway

36. Case 5

37. Surgical consideration

38. Patient selection General condition Age Liver regeneration power
Chemotherapy, cirrhosis
Precise volumetry
too much or too less?
ICG test ?

39. Procedure and Technique
Non-touch technique (no mobilization of right liver)
Avoid Tumor spreading and adhesion
Bile duct ligation/division
Induce atrophy of disease liver, bile leak ↑
Middle hepatic vein preservation
Increase the risk of ischemia, hepatic necrosis and subsequent bile leak

40. Middle HV sacrificed
Middle HV preserved

41. Time to reoperation Short interval to re-operation
Between 1 to 2 weeks
Enough hypertrophy, less adhesion
Longer period (>2 weeks)
progress after the first stage do not have favorable tumor biology, and are likely to have early recurrence following ALPPS
K.A. Bertens Intl J Surg 13 (2015)

42. Risk of tumor progression
Pre-apple treatment
Down size / stage
Biological selection
Risk of tumor progression

43. Conclusion ALPPS extended the possibility of R0 resection of HCC
Difficult procedure and High morbidity and mortality rate
Selection and drop out criteria are not established yet
Data of long term follow-up is still lacking