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2010 တုန္းကလုပ္ထားတဲ့ slide ေလးပါ..
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HEPATOCELLULAR CARCINOMA
Presented by
HO. Myo Mg Mg
Liver Unit, MGH
23.11.2010
• 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 factors
1. 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
agentSymptomatic
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.
THANK
YOU