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

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

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

What is allps

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

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

Case Report

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

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

12/03 second stage right lobe:936cm3, left: 540cm3 (0.729%) lab: Hb = 11.2 . PLT = 131,000. T-bil = 1.35, Alb=3.4 Left lobe volume increasing rate: (540-310)/310 = 74.5%

Material and Method

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 > 100000 /ml

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

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

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

Results

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%

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

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% (586-379/379) 52% 1.53 9 2 345 700 653 61% (653-405/405) 1.47 8 3 275 400 540 74% (540-310/310) 48% 1.35 15 4 268 150 500 45% (500-346/346) 43% 0.92 6 5 247 300 615 77% (575-325/325) 1.56 16 347 270 595 67% (525-315/315) 47% 1.37

Result number morbidity recurrence Follow period (m) AFP (ng/ml) 1 N 15 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

Discussion

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

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

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

Why do ALPPS be superior ? Faster and Larger Prevent collaterals and communications completely Parenchymal transection trigger liver regeneration K.J. Riehle, Hepatol. 26 (2011) 203-212 K. Abshagen. Langenbecks Arch. Surg. 397 (2012) 579-590.

Complete 2nd surgery: ALPPS 86% : PVE 66% Hypertrophy: ALPPS 77% : PVO 34% E. Schadde. World J. Surg. 38 (2014) 1510-1519.

Outcomes

Mortality and morbidity Long term follow up

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

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) 829-838.

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) 280-287

Increased proliferative activity of HCC ?

Liver regeneration vs. Carcinogenesis Same stimulators Same pathway

Case 5

Surgical consideration

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

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

Middle HV sacrificed Middle HV preserved

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) 280-287

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

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