Surgical Resection

2019. 2. 15

고려대학교 구로병원

최새별

Real practical process

before and during treatment for HCC

Contents

Introduction

Practice Guideline

Assessment of Liver Function

Surgical Strategy

Conclusion

Introduction

HCC occurs mainly in patients with cirrhosis, a condition that

increases the risks when performing potentially

curative surgical therapy

The safety of surgical resection has greatly improved because of

advances in radiologic assessment, patient selection, and

perioperative management

The operative mortality rate for hepatectomy has decreased less than

5%.

Relative merits of hepatectomy, ablation therapy, TACE, radiation

therapy liver transplantation → combination of these modalities to

best extend patients’ survival

Practical process of surgical resection to improve outcome

간세포암 의심

일차검사

(필수 검사 (Echo추가 :심혈관 질환 및 당뇨병의 기왕력), 선택검사)

일차판단 (간세포암 확진 및 수술 가능성 판단)

수술 가능 : 전신 마취 가능

수술 불가능 : 간기능 저하, 동반된 전신질환, 수행능력 저하, 수술거부

이차검사

(ICG, CT, Bone scan, PET, 간동맥조영술, 위내시경)

이차 판단 (절제 가능성)

국소적, 잔존 간기능 적절

진료 방침

복강경 혹은 개복

추적 검사

간세포암 치료 권장사항 V2

Surgical Outcome of HCC

Author Year N 3-YSR (%) 5-YSR (%)

Takenaka 1996 208 70 50

Chen 1997 382 52 46

Fong 1999 154 54 37

Llovet 1999 77 62 51

Hanazaki 2000 386 51 34

Poon 2001 136 47 36

Kanematsu 2002 303 67 51

Belghiti 2002 300 57 37

Ercolani 2003 2204 63 43

Shimozawa 2003 135 73 55

Kaibori 2007 285 69 55

Choi 2008 163 74 66

Kamiyama 2010 504 - 66

Practice Guideline for Surgical Resection

Practice Guideline

BCLC (Barcelona Clinic Liver Cancer)

Modified BCLC staging system

Optimal surgical candidacy ; Child-Pugh class A liver function with MELD

score <10, to be matched with grade of portal hypertension,

acceptable amount of remaining parenchyma

possibility to adopt a laparoscopic/minimally invasive approach.

The combination of the previous factors should lead to an expected

perioperative mortality <3% and morbidity <20% including a postsurgical

severe liver failure incidence <5%.

AASLD

Should adults with Child pugh class A cirrhosis

and early stage HCC (T1 or T2) be treated with

resection or locoregional therapy?

→The AASLD suggests that adults with Child-Pugh

class A cirrhosis and resectable T1 or T2 HCC

undergo resection over radiofrequency ablation

EASL

Indications for resection of HCC in cirrhosis should be based on multi-

parametric composite assessment of liver function, portal

hypertension, extent of hepatectomy, expected volume of the future

liver remnant, performance status and patients’ co-morbidities

LR is recommended for single HCC of any size and in particular for

tumours >2 cm, when hepatic function is preserved, and sufficient

remnant liver volume is maintained

HCC presenting with two or three nodules within Milan criteria may be

eligible for LR according to patient performance status, co-morbidities

and preservation of liver function and remnant volume

HCC-related macrovascular invasion is a contraindication for LR.

Intervention on distal portal invasion – at segmental or sub-segmental

level – deserves investigations within prospectively designed

protocols

Neoadjuvant or adjuvant therapies are not recommended

Assessment of Remnant Liver Function

잔류 간기능 평가

Child Pugh Class MELD

Child Turcotte Pugh

Model for End-stage Liver Disease (MELD) score

MELD 점수 = 3.8Ⅹloge(bilirugin[mg/dl]) + 11.2Ⅹloge(INR) + 9.6Ⅹloge

(creatinine[mg/dl]) + 6.4Ⅹ(간질환의 원인, 알코올성 또는 담즙정체성

간질환인 경우 0, 그 외 1)

1점 2점 3점

Albumin (g/dl) > 3.5 2.8-3.5 < 2.8

Bilirubin(mg/dl) < 2.0 2.0 – 3.0 > 3.0

PT % > 65 40 – 64 < 40

초(sec) 4 4 - 6 > 6

INR <1.7 1.7 - 2.3 > 2.3

복수 없음 중등도 ( 불응성

간성혼수 (등급) 없음 Ⅰ-Ⅱ Ⅲ-Ⅳ

간기능 평가

간혈류 측정; Indocyanine green (ICG),

Bromsulphalein (BSP), Radiolabeled bile acid

간대사기능 측정; lidocaine (MEGX), aminopyrine,

phenacetin, galactose, glucose (KBR), LiMAx

동위원소 검사

HVPG (Hepatic Venous Pressure Gradient)

ICG test

Indocyanine Green (ICG) test

ICG 15분 정체율 (ICG-R15) ;

ICG 정맥주사 ICG+Albumin+ α-1-lipoprotein간에서 일차순환시 선택적

유입담즙 배출

-장간 순환이나 신장배설은 되지 않는다.

- ICG의 수송은 빌리루빈과 동일한 운반체로 운반,

- 폐쇄성 황달; ① ICG 와 빌리루빈이 운반체에 경쟁적 결합을 하게 되어,

경쟁적 수송

② 분광광도계를 이용하여 흡광도를 측정, 위상승(false

elevation) 효과 초래

-혈청 빌리루빈이 2mg/dl이하로 떨어져야만 결과에 신빙성을 부여할 수가 있다

ICG 혈장 소실률 (ICG K)

ICG K=0.693/T1/2

T1/2 ; 혈장색소 반감기, 0.693; 2의 log값

Makuuchi’s Criteria in Japan

간섬유화 스캔

Transient elastography (FibroScan)

정상 간기능을 가진 경우 간섬유화 스캔 값은 평균 5.5±1.6 kPa

간세포암으로 수술하는 환자의 수술전 간기능 및 간경화도를 예측

간섬유화가 없거나 미약한 경우 2.5-7 kPa 정도이며, 12.5 kPa 이상(~75

kPa)인 경우 간경화로 진단할 수 있음 (Castera et al., 2008)

만성 간질환을 동반한 간세포암의 간절제술 후 간부전 발생과 간섬유화

수치의 연관성 을 연구한 논문에서 간섬유화 수치가 수술 후 간부전 발생 을

예측할 수 있는 유용한 도구이며, 수술 전 간경화도가 25.6 kPa 이상인

환자에서 수술 후 간부전이 발생할 위험 도가 증가 (Kim et al, 2008).

Liver Resection ; volume

Liver volume ; how much parenchyma could be

preserved?

Evaluation of Remnant Liver Function

Volume 간용적 측정

Portal Vein Embolization

Indication of PVE

Functional criteria; Child A, no PHT, tolerable ICG

FLR criteria; vol %

Anatomic criteria; no tumor thrombi, vascular anomaly

Liver Cancer 2012;1:159-167

Surgical Strategy ; ALPPS Associating Liver Partition and Portal vein Ligation for Staged hepatectomy

Right portal vein ligation combined with in situ splitting induces rapid left lateral

liver lobe hypertrophy enabling 2-staged extended right hepatic resection in

small-for-size settings.

World J Surg 2014;38:1498-1503

Surgical Planning & Strategy

간절제술 Surgical Strategy

Operative Design

Anatomical resection

vs Non-anatomical resection

Open vs Laparoscopy

Anatomical vs Non Anatomical resection

Micrometastases disseminate via

portal venous branches

Anatomic liver resection

providing systematic removal of the

tumour-bearing portal territories, with

exposure of the landmark veins

framing the segmental territory

anatomic resection is preferred over

nonanatomic resection in liver

resection carried out with curative

intent.

The incidence and patterns of HCC recurrence were similar between

the anatomical and nonanatomical resection. Recurrence by local

dissemination may be considered to be negligible in both surgical

methods.

Conclusions: In the propensity-matched cohort,

long-term outcomes of the Nonanatomical Lapa LR group

were not inferior to those of the Anatomical Lapa LR group.

Conclusions: Anatomical resection contributed to improve the

RFS rate in solitary HCC patients without macroscopic vascular

invasion using propensity score matching analysis, especially

in patients with MVI.

Conclusions; Anatomic resection decreases the risk of tumor

recurrence and improves OS in patients with a primary, solitary

HCC of <5.0 cm in diameter.(J Hepatobiliary Pancreat Sci (2017)

24:616–626

)

Resection margin

Incidence of micrometastases was closely related

to the distance from the primary HCC

an anatomic liver resection with a wider resection

margin theoretically gives a higher potential for a

cure

The optimal liver resection margin is still

controversial.

the aimed resection margin is different from the final

resection margin.

For macroscopically solitary HCC, a resection margin

aiming grossly at 2 cm efficaciously and safely decreased postoperative

recurrence rate and improved survival outcomes when compared with

a gross resection margin aiming at 1 cm, especially for HCC ≤2 cm.

(Ann Surg 2007;245: 36–43)

Conclu sions: A narrow resection margin (5 mm or less) does not detract from

oncologic outcomes after partial hepatectomy for HCC. Tailoring resection

margins may lead to greater preservation of hepatic parenchyma. Factors other

than margin status represent the driving forces for local and systemic

recurrence.(The American Journal of Surgery 214 (2017) 273-277)

Laparoscopic liver resection

pure laparoscopy, hand-assisted laparoscopy, and the hybrid

technique

And the consensus of best indication for laparoscopic liver

resection is limited to selected patients; solitary lesion, 5cm or

less, located in the peripheral liver segments.

The laparoscopic left lateral sectionectomy should be

considered the standard treatment

The indication has been expanded

Lap segmentectomy

M/64, HCV, Child A

During Liver resection

Decrease Bleeding and Transfusion

Pringle maneuver

Low CVP

Avoid Ischemia and congestion ; anatomy, IOUS

Transfusion and Worse outcome

Receipt of RBCT is associated independently with perioperative M & M

and prolonged hospitalization after partial hepatectomy

The mechanism

Transfusion-related immunomodulation

Impairment in immunity created by transfusion

Hypotheses; decrease in natural killer cell function, T-cell function,

increased number of suppressor T cells, and impaired macrophagic

and monocyte functions.

Inflammatory cytokines and other bioactive molecules being

generated with prolonged storage

Transfusion ; worse long-term outcomes,

including cancer recurrence and survival

Surgery 2016;159:1591

Control of inflow and outflow system during hepatectomy

Pringle maneuver ; total inflow occlusion

The time limit for clamping is 10–15 min, followed by

5 min declamping.

Selective clamping

Conclusions: These results suggest that PM does not increase the risk of

tumor recurrence or decrease long-term survival. J Surg Oncol 2018;117:198

Lowering the central venous pressure (CVP)

Inflow occlusion(HA, PV)

hepatic veins, sinusoid ; bleeding

The pressure within the sinusoids of the liver parenchyma is directly

related to the pressure in the hepatic veins, which is directly related to

the pressure in the central veins.

The hypothesis was that a low pressure in the central veins would be

accompanied by a low pressure in the hepatic veins and sinusoids,

thereby decreasing blood loss during transection of the liver

parenchyma.

The estimated blood loss from the outflow system

strongly correlates with central venous pressure (CVP)

In particular, keeping the CVP below 5 cmH2O is very effective at

reducing bleeding during liver resection

The remnant liver after hepatectomy may have inadequate blood supply,

especially following nonanatomical resection or vascular damage.

328 pts

Remnant liver ischemia was defined as reduced or absent

contrast enhancement during the venous phase. Remnant liver ischemia was classified as

minimal (none or marginal) or severe (partial, segmental, or necrotic).

radiologic signs of severe RLI were found in 98 patients (29.9%), of whom 63,

16, and 19 had partial, segmental, or necrotic RLI, respectively. These patients experienced

more complications and longer hospital stay than patients with minimal RLI.

Severe remnant liver ischemia was an independent risk factor for overall survival (OR, 6.98;

95% CI, 4.27-11.43; P < .001) and disease-free survival (OR, 5.15; 95% CI, 3.62-7.35; P < .001).

Preventive management and technical refinements in hepatectomy are

important to decrease the risk of RLI and to improve survival of

patients with hepatocellular carcinoma.

Special consideration

Portal hypertension

Volume preserving surgery

Huge HCC

PV invasion or BD invasion

Portal hypertension

Although clinically relevant portal hypertension (CRPH;

(defined as HVPG >10 mmHg) is a significant prognostic factor

affecting survival

11 publications

The final pooled data were composed of 2,285 patients.

There were 775 PHT group and 1,510 non-PHT group

Pooled proportion of mortality was 6.1% in PHT group and 2.8% in the

non-PHT group.

The pooled proportion of morbidity was 41.7% in PHT group and

34.7% in non-PHT group.

Pooled data confirmed a significantly higher postoperative mortality in

the PHT group, with OR 3.02 ( P <0.001).

Surgical resection should be selected carefully with strict surgical

strategy in patients with clinically significant portal hypertension

when surgical resection is planned.

J Hepatobiliary Pancreat Sci

2014;21:639-647

Special consideration

Portal hypertension

Volume preserving surgery

Huge HCC

PV invasion or BD invasion

Volume Preserving Surgery

J HBP Sci 2004;11:390-396,

Am J Surg 2005; 189:195-199

Rt ant segment; ventral and dorsal segment← Anterior Fissure

Right liver; right anterior, middle and posterior segment

To resect tumors infiltrating to the right hepatic vein at its root, right

hemihepatectomy or that following portal vein embolization (PVE) is

applied.

If the IRHV is sizable, the IRHV preserving liver resection can be

another option, a safe and useful procedure.

Dig Surg 2014;31:377–383

Segment 7,8

M/74

Child A, HBV

ICG R15 22.2%

Bisegmentectomy (7,8)

RHV

Case; central bisectionectomy Strategy for the preservation of liver volume

M/44

HBsAg (+)

Child A, 5

ICG R15 13.7%

2014.8.

central

bisectionectomy

HCC

1) Size of tumor : 8x7.1x6cm

2) Gross type : expanding nodular

3) Histologic pattern : trabecular

4) Tumor cell group : classical and clear cell

5) Tumor differentiation(Edmondson-Steiner's histologic grade)

- The worst grade(III/IV), The most grade(II/IV)

6) Tumor necrosis : 10%

7) Vascular invasion : present(focal and peritumoral)

8) Surgical margin : free of tumor

- safety margin : 0.2cm

9) Pathologic staging : pT2NX(AJCC)

(Seg 4,5,8; anterior section and medial section)

Special consideration

Portal hypertension

Volume preserving surgery

Huge HCC

PV invasion or BD invasion

Anterior approach right hepatic resection

Conventional approach ; Complete mobilization of the right liver with the

righthepatic vein controlled outside the liver before parenchymal transection ; mobilization 후 실질 절제

The technique

1) initial vascular inflow control,

2) parenchymal transection

3) venous outflow control

4) the right liver is mobilized

Conclusion: The anterior approach results in better operative and

survival outcomes compared with the conventional approach. It is the

preferred technique for major right hepatic resection for large HCC.

(Ann Surg 2006;244: 194–203)

Surgical method; Hanging Maneuver

Case ; Huge Hepatocellular Carcinoma

M/55

2006. 5. 14

M/55

DM, Hepatitis B

Chronic alcoholics

Child A, 5

ICG R15 13.8%

HBSAg (+)

Right Trisectionectomy

(segment 4,5,6,7,8)

(anterior, posterior, medial section)

Case ; huge HCC M/70

nonB nonC, alcoholics (-)

RUQ pain 주소로 내원

165cm, 80.4kg

AFP 7.2ng/ml ICG ; 18.4% (17.1%)

IMP)

. Suspected hepatocellular carcinoma in the right lobe of the liver.

DDx. Combined type 의 HCC + CCC 의 가능성 있겠음.

. Cholangiocellular carcinoma 단독의 경우는 가능성이 매우

떨어짐.

ICG ; 18.4% (17.1%)

Special consideration

Portal hypertension

Volume preserving surgery

Huge HCC

PV invasion or BD invasion

HCC with Bile Duct tumor thrombus, BD invasion

M/47, nonB nonC

ICG R15 13.7%, AFP 2.8ng/ml

HCC with Bile duct tumor thrombus (BDTT)

257 pts, Korea – Japan, 32 centers

Overall survival and recurrence rate at 5 years was 43.6% and 74.2%,

respectively.

Both performing liver resection equal to or greater than

hemihepatectomy and combined bile duct resection significantly

increased overall survival

Conclusions: Clinical outcomes were mostly influenced by tumor stage

and underlying liver function, and the impact of BDTT to survival seemed

less prominent than vascular invasion. Therefore, an aggressive surgical

approach, including major liver resection combined with bile duct

resection, to increase the chance of R0 resection is strongly

recommended.

HCC with Portal Vein invasion (PVTT)

PVTT can be graded asPV1 (segmentary), PV2 (secondary order branch), PV3 (first order branch), PV4 (main trunk/contralateral branch)

EASL; LR can only be considered for PV1/2 extension of HCC, and

only then as an option to be tested within research settings and not to

be considered a standard of practice.

Japan multicenter study, multicenter, 6474pts HCC with PVTt, surgery

2093pts

As long as the PVTT is limited to the first-order branch, LR is

associated with a longer survival outcome than non-surgical

treatment.

Conclusion

To eradicating the HCC and preservation of hepatic function

;surgical strategy

Assessment of resectabiliaty, future remnant liver function and

volume

Appropriate choice of procedure, surgical planning

During liver resection, to decrease blood loss, transfusion and to

avoid ischemia and congestion is necessary

Consideration of specific condition ; appropriate surgical plan

PHT, huge HCC, ruptured HCC, Bile duct turmor thrombosis, PV

thrombosis