HEPATOCELLULAR CARCINOMADR. ANANDRAJ

• Introduction• Pathogenesis • Clinical

Features

• Investigations• Management • Prevention

Introduction The most common primary tumor Sixth most common CA

• Incidence – 28/100,000 in SEA

(d/t increased prevalence of HBV inf)– 10/100,000 in South EU – 5/100,000 in North EU

(d/t increase incidence of HCV related cirrhosis)

Pathogenesis • The precise mechanisms of carcinogenesis

– unknown• Repeated circle of cell death & regeneration

mutation of hepatocytes• Preneoplastic changes – hepatocytes

dysplasia can be seen.

Aetiological factors1. Viral infection (repeated circle of cell death &

regeneration)2. Aflatoxins

(mutation in proto-oncogene/tumor suppressor gene, p53)

3. Cirrhosis (inflammation of the hepatocytes)

• Others – Age – Sex – Chemicals– Viruses – Hormones– Alcohol – Nutrition

• The most important HVB infection(100 folds increase in risk to develop HCC)

• COL (-) – 0.4% per year (+) – 2-6% per year HCC

• 75-90% of HCC pt - COL (+)

Morphology• Gross

– 3 types• Unifocal • Multifocal • Diffusely infiltrative

– Unifocal lesion mostly seen in pt without COL– Multifocal lesion mostly seen in pt with COL

• Microscopic appearance

– Well to moderately differentiated tu – nearly similar to the n/l hepatocytes

– Poorly differentiated tu – pleomorphoic

• Spread

– Tend to spread by invasion into the vasculature, mostly the portal vein

– Highly metastases to lymph nodes– Lung & bone metastasis are not uncommon

and seen in terminal cases

Clinical Features • Seldom characteristics• Masked by the underlying liver disease• May present with features of chr. VH or

COL• May c/o about ill-defined abd

pain/discomfort, fullness of abd, malaise, fatigue, LOA and LOW.

• Examination may reveal hepatomegaly or a right hypochondrial mass.

• Tumour vascularity can lead to an abdominal bruit, and hepatic rupture with intra-abdominal bleeding may occur.

Investigations(i) Serum alpha feto-protein • Produced by 60% of HCC• Level depends on size of tu• May be n/l in small tu• Both sensitivity and specificity – low • Can be high in presence of HBV & HCV

replication and a/c liver necrosis

• Should be used in conjunction with other imaging techniques

• In the (-)ce of obvious liver disease, if there is increasingly rising AFP or AFP > 400 ng/ml, HCC must be search aggresively.

(ii) USG

• Can show small tu about 2-3cm• Also portal vein involvement and

coexisting COL• USG contrast agent can also be used

(iii) CT and MRI

• Contrast enhanced helical CT can show HCC – hypervascular appearance.

• MRI can also be used instead of CT.• But tumors <2cm – difficult to differentiate

from hyperplastic nodule of cirrhosis.

(iv) Liver biopsy• To confirm the diagnosis & exclude

metastasis tu from other• Done in pt with large tu, no COL and HBV

inf• Avoid in pt eligible for transplantation or

surgical resection (<2% risk of tumor seedling along the needle tract)

Tumor Staging Systems• Various systems used to determine the

stages of HCC• Most of them describe the prognosis of

HCC depending upon – The severity of underlying liver d/s– The size of tumor– Extension of tumor into adjacent structures– Presence of metastasis

OKUDA SYSTEM

CRITERIA POSITIVE NEGATIVE

Tu. size >50% <50%

Ascities Clinically detectable Clinically absent

Albumin <3 mg/dl >3 mg/dl

Bilirubin >3 mg/dl <3 mg/dl

Stage Survival rate

• I – no positive 8.3 mth• II – 1 or 2 (+)ve 2 mth• III – 3 or 4 (+)ve 0.7 mth

• Does not stratify pt by vascular invasion or presence of nodal metastasis

• Not important for treatment (surgery)• Only pure clinical scoring system

TNM staging (American Joint Committee on Cancer )

• This system recognizes the most important predictors of prognosis

The number and size of tumor Extent of vascular invasion Condition of regional lymph node Presence or absence of metastasis

Primary tumor• TX – primary tu cannot be assessed• T0 – no evidence of primary tu• T1 – solitary tu without vascular invasion• T2 – solitary tu with vascular invasion• T3a – multiple tu more than 5 cm• T3b – single or multiple tu of any size

involving maj branch of portal vein of hepatic vein

• T4 – tu with direct invasion of adjacent organs other than gallbladder or with perforation of visceral peritoneum

Regional lymph node• NX – regional lymph cannot be assessed• N0 – no regional lymph metastasis• N1 – regional lymph metastasis

Distant metastasis• M0 – no distant metastasis• M1 – distant metastasis

Five year survival rates

• Stage I – 55%• Stage II – 37%• Stage III – 16%• Stage IV <16%

Barcelona Clinic Liver Cancer System• Considers in combination of tu burden,

hepatic function and performance status together with evidence based treatment argorithm

• Can provide not only the prognosis but also the treatment plan

STAGE TU BURDEN CHILD-PUGH

PST MEDIUM SURVIVAL

Very early (0) Single tu <2cm A 0

Early (A) Single tu <5cm or3 tu <3cm each

A-B 0-2 53 mth

Intermediate (B) Single tu >5cm orMultiple tu largest >3cm

A-B 0-2 16 mth

Advanced (C) Any tu burden A-B 1-2 7 mth

Terminal (D) Any tu burden C >2 3mth

Hepatocellular carcinoma

Very early stage Early stage Intermediate stage

Terminal stage

Advanced stage

Single 3 nodules

Portal pressure

Normal

increase Asso: d/s

Resection Transplantation

Yes No

Ablation Chemo-embolisation

Newer agent

Symptomatic

Management options

• Hepatic resection• Liver transplantation • Transarterial chemo-embolization

Hepatic resection • Treatment of choice for non-cirrhotic pt• 5yr survival rate – 50%• Recurrence rate at 5 yr – 50%• Can be consider in cirrhotic pt with small tu

and good liver functions (risk of a/c liver failure)

• Tu clearence margin at least 1-2cm• In COL pt, the volume of resection must be

minimized to avoid post-operative liver failure

Liver transplantation• Curative treatment for cirrhotic pt • 5 yr survival rate – 75%

Transarterial chemo-embolisation• Embolisation of hepatic artery with

gelfoam and doxirubicin• Used in pt unresected HCC and good liver

function• Contraindicated in pt with cirrhosis and

multifocal HCC• Survival rate 60% at 2 yr and lost in 4 yr.

Radio-frequency ablation• used to produce coagulative necrosis of ca

cells

Prevention • As viral infection with HBV is the most

important aetiology and HBV vaccination is already avaliable, vaccination should be done.

• Consider about the universal precaution in handling infected blood and its products in medical personal

• Reduce the risk of vertical transmission of hepatitis viruses

• Early diagnosis and prompt treatment– To get early diagnosis, screening procedures

should be done in endemic area – All pt must be given prompt treatment after

being diagnosed as HCC or chr. hepatitis

• So that tu burden will be reduced and QOL of the pt will improve.

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