4. Pathogenesis
• The precise mechanisms of carcinogenesis
– unknown
• Repeated circle of cell death & regeneration
mutation of hepatocytes
• Preneoplastic changes – hepatocytes
dysplasia can be seen.
5. Aetiological factors
1. Viral infection
(repeated circle of cell death &
regeneration)
2. Aflatoxins
(mutation in proto-oncogene/tumor
suppressor gene, p53)
3. Cirrhosis of liver (COL)
(inflammation of the hepatocytes)
6. • Others
– Age
– Sex
– Chemicals
– Viruses
– Hormones
– Alcohol
– Nutrition
7. • 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 (+)
8. Morphology
• Gross
– 3 types
• Unifocal
• Multifocal
• Diffusely infiltrative
– Unifocal lesion mostly seen in pt without COL
– Multifocal lesion mostly seen in pt with COL
9. • Microscopic appearance
– Well to moderately differentiated tu – nearly
similar to the hepatocytes
– Poorly differentiated tu – pleomorphoic
10. • 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
11. 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.
12. • 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.
13. 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
14. • 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 searched
aggresively.
15. (ii) USG
• Can show small tumor about 2-3cm
• Also portal vein involvement and
coexisting COL
• USG contrast agent can also be used
16. (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.
17. (iv) Liver biopsy
• To confirm the diagnosis & exclude
metastasis from other sites
• 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)
18. 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
20. Stage Survival rate
• I – no positive
• II – 1 or 2 (+)ve
• III – 3 or 4 (+)ve
8.3 mth
2 mth
0.7 mth
21. • Does not stratify pt by vascular invasion or
presence of nodal metastasis
• Not important for treatment (surgery)
• Only pure clinical scoring system
22. 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
23. 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
26. Five year survival rates
• Stage I – 55%
• Stage II – 37%
• Stage III – 16%
• Stage IV <16%
27. 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
28. STAGE TU BURDEN CHILD-
PUGH
PST MEDIUM
SURVIVAL
Very early (0) Single tu <2cm A 0
Early (A) Single tu <5cm or
3 tu <3cm each
A-B 0-2 53 mth
Intermediate (B) Single tu >5cm or
Multiple 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
29. 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
31. 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)
32. • Tu clearence margin at least 1-2cm
• In COL pt, the volume of resection must be
minimized to avoid post-operative liver
failure
34. 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.
36. 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
37. • 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.
