Department of Hepatobiliary Oncology,SYSUCC

Anti-liver cancer team

Shengping Li, M.D., Ph.D

•Advanced stage

•Low resection rate

•High recurrence

•Decompensation liver function

Poor prognosisFierce

Liver cancer

PLC (Primary Liver Cacner)

Secondary Liver Cancer

HCC(Hepatocellular carcinoma)

CCC(Cholangiocellular carcinoma)

HCC

HCC and CCC mixed

Epidemiology

“Hot spots” – 150 per 100 000

US, Australia : 2 per 100 000

•The fifth most common

cancer worldwide

•CA Cancer J Clin 2005

High incidence In China

• Shanghai

• Jiangsu

• Fujiang

• Guangdong

• Guangxi

Epidemiology

Trend of Death rate of malignant Trend of Death rate of malignant tumor in China tumor in China

LungLiverStomach

1282004-2005

StomachLiverLung

1061990-1992

Stomach EsophagusLiver

801973-1974

Three leading causes of Ca. death

Death Rate(per100,000)

Period(years)

EtiologyEtiology

Hepatitis

Alcoholism

Environmental factors

molecular and Cytogenetic alterations

HBV 80% (Asia and Africa),

100 million china

HCV 70% (Japan,West count

ries)

Hepatitis virus infectionHepatitis virus infection

Alcoholism: alcoholic cirrhosis

Food contaminated with aflatoxin

Decayed peanut,corn

Turkey Liver cancer

Liver Flukes (Clonorchis sinensis )

Liver Flukes InfestationLiver Flukes Infestation

Mutation of oncogene and tu

mor suppressor gene

（癌基因和抑癌基因的突变） N-ras,c-myc,cfms,CSF-1R, IGF

-II ， p53 ， TTR, DLC-1, LPTS, W

FDC1, HCCS1, HCRP1, 17HSDB2

Chromosomal alterations

( 染色体改变）

Gain （获得） :1q,8q and 20q

Lose （缺失） : 4q,8p,13q,16q

,

and 17p

( Li SP, et al . J Hepatology 2001)

Molecular and cytogenetic aberration

（分子和细胞遗传学变异）

Peoples lived in high incidence of liver cancer area

Peoples persistent infection of hepatitis virus

Family history of liver cancer

Liver cancer history previously

High Risk Group

Early stage Subclinical stage

Non symptom and sign

Clinical manifestation

• Abdominal pain and distention

• Weight loss

• Hepatomegaly ： 80%

• Abdominal mass

• Jaundice ,ascites

Clinical stage

Diagnosis of HCCDiagnosis of HCC

Serological (tumor markers)

Radiological

Cytological

Histological

Either alone or in combination

Tumor markers for HCCTumor markers for HCCMost common used

Diagnostic Imaging for Diagnostic Imaging for HCCHCC

Radiology--USRadiology--US

Ultrasound– Availability, cost– Operator

dependant– Therapeutic role.

Radiology--CTRadiology--CT

Triphasic CT – detect 30 – 40%

more tumour nodules than conventional CT.

Lipiodol – Retained by all

hypervascular liver tumours.

Radiology--MRIRadiology--MRI

Slightly higher sensitivity than CT in detecting hepatic lesions.

Cost, availability.

Diagnosis and treatment simultaneously

Invasive, not routinely used

Radiology--angiographRadiology--angiograph

• Expensive

• Whole body sca

ning

• Tumor cell Funct

ion

Radiology--Positron Emission computed Tomography, PET/CT

Liver BiopsyLiver Biopsy

Biopsy now rarely required to diagnose HCC.

Avoid biopsy of potentially resectable tumour.– Risk of needle track seeding 1 – 3%– Risk of bleeding

US and CT most commonly used clinically

Diagnostic imaging for Diagnostic imaging for HCCHCC

1. AFP≥400 ng/L, palpable mass or space-occupying

lesions in the liver by imaging

2. AFP<400 ng/ L, specific liver cancer images confir

med by at least two kinds of imaging scanning

3. Clinical manifestation of liver cancer with patholog

ical diagnosed extrahepatic liver cancer and meta

stases liver tumor ruled out

Standard rule for Diagnosis of HCC

Clinical Application of Clinical Application of AFPAFP

1.Screening of liver cancer

2.Dianosis of liver cancer

3.Predicting prognosis after treatment

4.Surveillance of recurrence after

treatment( decrease to normal level

within 1-2 months after resection)

Differential diagnosisDifferential diagnosis

AFP positive

chronic active hepatitis, cirrhosis, testicular tumor,

pregnancy

AFP negative

haemangioma, metastatic liver carcinoma, absces

s, focal nodular hyperplasia (FNH), hepatic hydatid

osis

Pregnancy with HCC

Delivery baby and resection of HCC simultaneously

Hepatic haemangioma

Colon cancer liver Colon cancer liver metastasismetastasis

Focal Nodular Hyperplasia Focal Nodular Hyperplasia (FNH)(FNH)

Hepatic AbscessHepatic Abscess

Hepatic Hepatic HydatidosisHydatidosis

Therapeutic Option for Therapeutic Option for HCCHCC

SurgerySurgery

Langenbuch 1888 first left hepatic

lobectomy Tiffany 1890

first liver resection for solid tumour

Starzl 1963 first liver

graft

Principles of Surgical Principles of Surgical ManagementManagement

Determining resectability

Stage of tumour

Functional hepatic reserve

80%-90% of HCC occur in cirrhotic livers

Less than 20% of patients with HCC are candidates for resection at time of presentation.

1. Staging1. Staging

TNM– Stage III, IV unresectable

Okuda CLIP (Cancer of the Liver Italian Program) Barcelona Staging Classification

– Performance scores, Okuda, tumour morphology

French Staging Classification– Performance scores, LFT, US

TNM Staging System

stagingstaging

Because the combined impact of liver diseaseand tumor burden is not yet fully understood, andthe cause of HCC may vary geographically, noneof the currently used staging systems fulfils all therequirements for stratification of patients with HCCinto groups of different prognosis and therapeuticrecommendations. None of the staging systems isuniversally accepted.

2. Functional Reserve2. Functional Reserve

Resection only of benefit in patients with adequate functional reserve.

Assessment of liver function : – Synthetic capacity of liver

» Serum albumin, prothormbin time

– Excretion of metabolites» Indocyanine dye test, bilirubin, bile acid profile

– Child-Pugh Classification

Child Pugh ClassificationChild Pugh Classification

2. Functional Reserve2. Functional Reserve

Portal hypertension Estimation of likely remaining liver

volume after resection Comorbidities

– ASA / Performance scores– Nutritional state : Perioperative

nutritional support decreases post operative morbidity

5-year survival 26-50%, mean 30%

5 years recurrence rate is about 70%

A critical clinical problem

Hepatectomy

6 mPre-op

Cutting edge recurrence

Liver transplantationLiver transplantation

• Potentially resect HCC while replacing the cirrhotic liver

• Milan criteria for HCC

Single lesion <5cm or upto three lesions <3cm

LimitationLimitation

Immunosuppression– Recurrent hepatitis– Recurrent HCC

Shortage of donors – Consider “bridging therapy” to

prevent tumour progression.– Living donors

Non Surgical Management Non Surgical Management Transcatheter Arterial Chemoembolization Percutaneous microwave coagulation therapy Percutaneous ethanol injection Radiofrequency Ablation Cryosurgery Systemic Chemotherapy Hormonal therapy Immunotherapy Gene Therapy Chinese medicine

Percutanous interventiPercutanous interventiononPEI: percutanous ethanol injection

RF: Radiofrequency ablation

MCT: microwave coagulation thermotherapy

LT: Laser thermotherapy

Cryoablation

Best option for small unresectable HCC

　　　　将 10枚象“弹头”一样的小电极通过穿刺针管送入癌组织，多枚小电极从不同的角度和方向“锁定”癌症组织区域，由计算机测算出射频治疗所需的最佳温度，时间，功率和阻抗，由小电极发出高能射频波，在 100

—120℃的高温下，使癌组织蛋白发生凝固性坏死，达到杀灭癌组织的效果。

3.5cm/15G 10 electrodes Lee Veen needle

Radiafrequency ablation,RF•Alternative to PEI

•Applied percutaneously,laparoscopically, during laparotomy

•Expensive but offer a better local control

•Ablation of tumor large than 5 cm in diameter

• The most widely used treatments for HCCs which

are unresectable or cannot be effectively treated with

percutaneous interventions.

•Embolization agents: Lipiodol,gelfoam

•Chemotherapeutics: doxorubicin, 5-Fu, mitomycin, cisplatin

•Partial responses in 15-55% of patients

• Delays tumor progression and vascular invasion

•Prolongs the survival time compared to conservative management.

TACE or TAE

TACE or TAE

•Patients liver function Child A

•Without vascular invasion or extrahepatic spread.

•Advanced liver disease (Child B or C), treatment-induced liver failure may offset the antitumor effect or survival benefit of the intervention.

•Postoperative adjuvant TACE may improve survival in patients with risk factors for residual tumor

Tumor shrinkage post-TACE

Principles of

management •Treatment in early stage

•Combination therapy

•Actively( time and again)

Metastasis of HCC

Intrahepatic ---port vein pathway, satellite

Extrahepatic: lung Lymphatic pathway: CCC Invasion periheaptic organs directly Abdominal implantation: tumor rupture

HCC metastasis

Continuing challenges

•Prevalance of chronic hepatitis

•Low resection rate

•High recurrence rate post-resection

•Shortage of liver donor

•Optimal combination therapy

•Molecular staging system

Thank you!Thank you!