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Current Surgical Management of Hepatoma/HCC Panayiotis Hadjicostas M.D., PhD, F.A.C.S. Chief, Department of Surgery LARNACA GEN. HOSPITAL
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Page 1: Current Surgical Management of Hepatoma/HCCcysurg.org/2013/images/Concress2013/omilies/HCC_GC... · Hepatocellular Carcinoma: Ablation Ablation: radiofrequency ablation (RFA), microwave

Current Surgical

Management of

Hepatoma/HCC

Panayiotis Hadjicostas

M.D., PhD, F.A.C.S.

Chief, Department of Surgery

LARNACA GEN. HOSPITAL

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Hepatocellular Carcinoma

17,000 new cases / year in USA

major cause of cancer death worldwide (5th)

•Associated with chronic liver disease (70 – 90%)

•10 – 30 % amenable & transplant or resection

no treatment: median survival 6-20 months

doubling time: median 6 months (range 1-19)

Ca-A Cancer 2001; 51:15-36

Semin Liv Dis 1993; 13:374-383

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Epidemiology

Alterkruse et al. JCO 2009

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Mortality

Alterkruse et al. JCO 2009

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Cirrhosis

Cancer

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B Vs C Does it matter?

• Hepatitis B:– 80% cirrhosis, most Child’s A, less portal HTN

– Often larger in size but tend to be more well –differentiated with less vascular invasion

– Effective medication to treat HBV

– Incidence of HCC is 0,5 – 2% per year

• Hepatitis C:– 100% cirrhosis, most Child B,C with portal HTN

– Moderately – differentiated, more likely to have microvascular invasion even in small tumors (2 – 3 cm)

– Incidence of HCV is 1,4 – 5,8% per year

– Correlation with degree of fibrosis and continue to rise over time

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HCC Vs CirrhosisMust consider survival related to cirrhosis independed of malignancy.

Child –Turcotte- 1year Liver

Pugh score Related mortality

5-6 (A) 0%

7-9 (B ) 20%

10-15(C) 55%

HCC in a cirrhotic Liver

with PHTN

Schneider Surg. Clin.N. America 2004

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Therapeutic Approach

Typical Malignancy

Liver Specific Factors

Cirrhosis / Fibrosis

Ascites

Portal Hypertension

Thrombocytopenia

Bilirubin

Size of Remnant Liver

Tumor Specific Factors

Size

Location

Number

Relation to adjacent

structures

Distant Spread

Hepatocellular Carcinoma

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Hepatocellular Carcinoma

Treatment and disease extend

• Local– Simple Tumor

– Milan Criteria

• Regional– Multifocal, liver

confined

• Systemic– Extrahepatic

metastasis

Resection

Transplantation

Ablation

Embolization

?Chemotherapy

Chemotherapy

?Embo + Chemotherapy

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Disease

Extent

Performance

Status

Hepatic

Functional

Reserve

Better Worse

Worse

Surgical Clinical Decision Making

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Surgical Treatment Options

Ablation:

Small Lesions

Inoperable/Unresectable

Bridge

Resection:

All size HCC

Normal liver and early

fibrosis/cirrhosis

Transplantation:

Single 5 cm and

Multiple 3 cm up to 3

Advanced cirrhosis

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Classical Contraindications

• Poor liver function (especially

portal HTN)

• Multifocal disease

• Major vascular invasion

• Major biliary invasion

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Recurence

• 75 – 100 % overall

• 78 – 96 % Intrahepatic

– Intrahepatic metastasis

– Micro/ macro – portal vein invasion

– New primary tumor

– Ongoing carcinogenesis

Poon Ann Surg 2000

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Surgical Resection: Liver Factors

• Quality of underlying liver

• Quantity of underlying liver

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0

10

20

30

40

50

60

70

80

90

100

Surgery in Patients with CirrhosisNon-transplant Operative Mortality by CTP Class

Garrison et al, Ann Surg 1984

Mansour et al, Surgery 1997

Garrison et al.

Mansour et al.

CTP-A CTP-B CTP-C

Peri

-Opera

tive

Mort

alit

y%

5-10%

9-30%

50-90%

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0 1 2 3 4 5 6 7

Years

Ris

k o

f Liv

er

Decom

pensation (

%)

≥ 10 mmHg

< 10 mmHg

Ripoll, et al. Gastroenterology 2007Bruix J, et al. Gastroenterology 1996

Non-decompensated

(n = 18)

Decompensated

(n = 11)

0

5

10

15

20

HP

VG

(m

mH

g)

Surgery in Patients with CirrhosisHepato-Portal Veinous Gradient (HPVG)

HPVG

1.0

0.8

0.6

0.4

0.2

0.0

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0 5 10 15 20 25 30 0 10 20 30 40 50 60 70 80 90

Days Following Surgery Days Following Surgery

100

80

60

40

20

0

Peri

-Opera

tive S

urv

ival (%

)

P < 0.001 P < 0.001

― 6-10 (n=432)― 11-15 (n=243)― 16-20 (n=68)― 21-25 (n=15)― 26-39 (n=10)

Teh et al. Gastroenterology 2007

Surgery in Patients with CirrhosisBiologic MELD and Post-Operative Outcome

30-Day Mortality 90-Day Mortality

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Liver Volumetry

Future Liver Remnant

(FLR)

40-50%

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Portal Vein Embolization (PVE)

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R. Liver L. Liver

Hepatic Hypertrophy

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Pre-operative portal vein embolization

ANNALS OF SURGERY

Vol. 237, No. 2, 208–217

© 2003 Lippincott Williams & Wilkins, Inc.

Portal Vein Embolization Before Right

Hepatectomy: Prospective Clinical Trial

Olivier Farges, MD, PhD,* Jacques Belghiti, MD,*

Reza Kianmanesh, MD,* Jean Marc Regimbeau,

MD,* Roberto Santoro, MD,* Valerie Vilgrain, MD,†

Alban Denys, MD,† and Alain Sauvanet, MD*

From the Hepatobiliary Service and Department of *Digestive

Surgery and †Radiology, Beaujon Hospital, Assistance

Publique, Clichy, France

Variable

Pre-Operative PVE

Yes (14) No (14) p

Mortality 1 1 0.8

Morbidity 7 13 0.012

Liver Failure 1 7 0.01

Hospital Stay

(days)13 4 30 15 0.002

Post-operative Course After R. Hepatectomy:

Patients with Chronic Liver Disease

Improved outcome in patients with chronic liver disease

Hepatocellular Carcinoma: Resection

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Surgical Resection: Tumor Factors

• Tumor size

• Tumor number (multi-focality)

• Presence of vascular invasion

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Barcelona-Clinic Liver Cancer Classification and Treatment Schedule

RFAblation

Curative treatment Palliative treatment

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Intermediate Stage HCC

or

“Group 2”

???

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Liau et al. Cancer; 104:1948-1955, 2005

Tumor Size

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Months

250200150100500

Pro

port

ion

Su

rviv

ing

1.0

.8

.6

.4

.2

0.0

T1

T2

T3

T4

P < .001

Tumor Size ≥ 10 cm

Pawlik et al. Arch Surg; 140:450-457, 2005

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Vauthey et al. J Clin Oncol; 20:1527-1536, 2002

Tumor Size + Tumor Number

Solitary Tumors Multiple Tumors

Vauthey et al. J Clin Oncol; 20:1527-1536 2002

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Morbidity Mortality

Ng et al. 27 2.2

Wang et al. - 2.7

Torizilli et al. 26 0

Bellevance et al. 49 2

Teh et al. - 0

Resection of Multi-Nodular HCC

Percent (%)

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Overall Survival 25-30%

Disease-Free Survival 18%

Wang et. al. 2008

Resection of Multi-Nodular HCC

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Multifocal Disease

• Classical Contraindication

• Intrahepatic Metastasis Vs synchronous

primary Tumors

• Very high recurrence( Universal?)

• Poor Survival ( < 25% 5 year)

• Selected patients can do well

• Selection criteria not well studied

• Ng Ann Surg Onc 2005

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Major Vascular Invasion

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Resection: Major Vascular Invasion

Portal Vein 5-yr Survival

Vp0 50%

Vp1 31%

Vp2 26%

Vp3 12%

Vp4 7%

Hepatic Vein 5-yr Survival

Vv0 43%

Vv1 19%

Vv2 11%

Vv3 0%

Ikai et al. Surg Oncol Clin N Am; 12:65-75, 2003

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Major Vascular Invasion

• Advanced Disease

• Technically challenging and risky

• Associated with large tumors

• Near Universal recurrence

• Poor survival (<20%)

• Occasional long term survival

Pawlik, Surgery 2005

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Pawlik et al. Surgery; 137:403-410, 2005N=101

Months

2001751501251007550250

Pro

porti

on S

urv

ivin

g

1.0

.8

.6

.4

.2

0.0

No or minimal fibrosis

Moderate or severe fibrosis

P = 0.001

Resection: Major Vascular Invasion

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Resection: Overall Survival for “All-

Comers”0.0

00.2

50.5

00.7

51.0

0

Perc

ent S

urv

ival

0 1 2 3 4 5Years

Resection Transplant

Survival by Surgery Type

Transplantation

Resection

66%

46%

79%

71%

P < 0.01

Bellavance , Pawlik. JOGS 2008.

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65% 5-year survival

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Resection Vs Transplantation

When is Resection “As Good” or Better

Normal Remnant Liver Parenchyma

• Child’s A Cirrhotic

– Total bilirubin (<1,5 mg/dl)

– Absence of portal HTN

• Platelets: >100000

• No varices

• Single Tumor

– Multiple Tumors often metastatic

– Hepatitis B Vs other

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Ablation:

Small Lesions

Inoperable/Unresectable

Bridge

Resection:

All size HCC

Normal liver and early

fibrosis/cirrhosis

Transplantation:

Single 5 cm and

Multiple 3 cm up to 3

Advanced cirrhosis

Surgical Treatment Options

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Hepatocellular Carcinoma: Transplantation

1. Only solid neoplasm for which transplantation

plays a role

2. Treats both the malignant disease and the

underlying hepatic parenchymal disease

3. Not restricted by liver function

4. Limited by:

• Disease extent (size and number: Milan criteria)

• Organ availability

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Author N Recurrence 5-Year Survival

Ringe ’91 61 - 15%

Iwatsuki ’91 105 43% 36%

Pichlmayr ’92 87 - 20%

Bismuth ’93 60 54% 49% (3 yr)

Moreno ’95 38 32% 48%

Results of early series: broad selection criteria

Hepatocellular Carcinoma: Transplantation

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Author N Recurrence 5-Year Survival

Mazzaferro ’96 48 8% 74% (4 yr)

Bismuth ’99 45 11% 74%

Llovet ’99 79 4% 75%

Jonas ’01 120 16% 71%

Hemming ’01 112 - 57%

Results of early series: restrictive criteria

Hepatocellular Carcinoma: Transplantation

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Expanding the Criteria: UCSF

• Single tumor < 6.5 cm or up to 3 nodules each less

than 4.5 cm and a total diameter less than 8 cm

• 1 year survival 90% and 5 year survival was 75%

• 1 yr survival 50% in patients with tumors larger than

6.5 cm

• Size cutoffs were based on retrospective review of

explants, not preoperative imaging

Yao FY, et al. Hepatology 2001;33:1394-1403.

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61 patients with disease exceeding UNOS T2

Solitary tumor: > 5 cm ≤ 8 cm

2 – 3 tumors: > 3 cm ≤ 5 cm

4 – 5 tumors: < 3cm

Down-staging protocol (≥ 3-month waiting period before transplantation)

Successful down-staging in 43 patients

Treatment failure in 18 patients

Tumor progression (15), death without OLT (3)

Yao et al. Hepatology 2008;48:819

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Yao et al. Hepatology 2008;48:819

Follow-up (years)

Kap

lan

-Me

ier

Pro

ba

bilit

y

0 1 2 3 4

0.0

1.0

0.8

0.6

0.4

0.2

Intention-to-treat Survival (n = 61)

Treatment Failure (n = 61)

69%

32%

Survival (4-year)

Intention-to-treat = 69%

Post-transplant = 92%

No recurrent HCC after transplantation

Median follow-up = 25 months

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Should LDLT Be Preformed for

Patients With HCC Exceeding the

Milan Criteria?• LDLT in pts outside Milan Criteria can be considered

justified since it involves the use of an individually available graft without penalizing other pt on the waiting list

• LDLT offers acceptable survival to pt who would otherwise die from liver failure following resection or

HCC / intrahepatic recurrence (SalvageTransplantation/… Ethical dilemmas..)

• The proportion of HCC pts not fulfilling the Milan Criteria that could be cured by LT ranges from 25-50%

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Ablation:

Small Lesions

Inoperable/Unresectable

Bridge

Resection:

All size HCC

Normal liver and early

fibrosis/cirrhosis

Transplantation:

Single 5 cm and

Multiple 3 cm up to 3

Advanced cirrhosis

Surgical Treatment Options

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Hepatocellular Carcinoma: Ablation

Ablation: radiofrequency ablation (RFA), microwave

Efficacy limited by several factors:

Size (> 5 cm)

Location (major vascular structures)

Tumor burden (multifocal disease)

Short follow-up, inadequate assessment of response

Associated morbidity and mortality

Analysis of ˜ 4000 procedures in Japan

♦Morbidity = 8%

♦Mortality = 0.3%

Kasugai et al Oncology 2007;72 (suppl 1):72

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Radiofrequency Ablation

Ideal Tumors for RFA are:

•Preferably <3cm but up to 5cm in diameter

•<4 in number

•Completely surrounded by hepatic parenchyma

• 1cm deep tp the liver capsule

•2cm from large hepatic or portal veins

•Not immediately adjacent to the diaphragm,

gallbladder or bowel.

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Thermal Ablation:

HCC vs. Colorectal Liver Metastasis

Soft Tumor + Hard Liver Hard Tumor + Soft Liver

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Resection vs. ablation for small HCC

Petrowsky et al J Hepatol 2008;49:502Hasegawa et al J Hepatol 2008:49;589

Hepatocellular Carcinoma: Ablation

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HCC: Resection vs RFA (single < 4cm Lesion)

148 Patients (Hep B/C)

Refuse Surgery Resection (93)

RFA (55)

No difference in 1 and 3yr recurrence free and overall survival

Hong et al, J. Clin.

Gastroenterology 2005; 39(3): 247

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NO DIFFERENCE

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FACTOR CATEGORY # CASES % RECURRENCE

Size

> 5 cm 31 58

3 – 5 cm 106 25

≤ 3cm 1680 14

Pathology

HCC/Met Colorectal 3132 15

Other Metastatic 1046 10

Met Neuroendocrine 330 3

SubcapsularYes 13 62

No 57 16

Vascular

Proximity

Yes 104 37

No 271 3

Approach

Percutaneous 3002 16

Laparoscopic 515 6

Open 907 4Mulier et al Ann Surg 2005;242:158

Local recurrence after RFA: 5224 treated tumors

Hepatocellular Carcinoma: Ablation

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Hepatology 2008;47:89

218 patients with HCC

Solitary

≤ 2 cm

1995 – 2006

5 Centers

One or two sessions

Follow-up = 31 months

Major morbidity = 2%

6 Treatment failures (2.7%)

Survival (5-year)

Disease-free = 20%

Overall = 55%

Operable = 68%

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291 patients 2001 – 2004

≤ 3 tumors

> 3 cm but < 7.5 cm

Free of major vasculature

Child’ A or B

Randomized: TACE, RFA, both

1378 patients screened

1087 excluded

Results:

45% solitary tumors

75% ≤ 2

3 – 4 courses of therapy

Median survival

TACE 24 months

RFA 22 months

TACE + RFA 37 months

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TACE

RFA 2nd RFA

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Pre-RFA Post-RFA

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Summary

• In patients with ‘small’ HCC: good results can be

obtained with all modalities

• Resection

• Best alternative for advanced tumors with well

preserved liver function

• Transplantation

• Best alternative for advanced cirrhosis or multifocal

disease

• Ablation

• Reasonable as 1st line therapy in patients with small

(2 - 3cm) tumors

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RESECTIONTRANSPLANTATION

Individualize Therapy NOT Dogmatic Approaches

• Underlying liver disease

• Tumor size, number, vascular invasion

• Location of lesion

• Performance status

• Local expertise

• ? Other factors: hepatitis status, wait time, etc.

ABLATION


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