I°Corso AIGO in Epatologia
La cirrosi virale: prevenzione e terapia.La cirrosi virale: prevenzione e terapia.
EpatocarcinomaEpatocarcinoma: algoritmo diagnostico: algoritmo diagnostico
F.FarinatiF.FarinatiGastroenterologiaGastroenterologia, Padova, Padova
Gestione dell’HCC: i problemi
1. Sorveglianza? E come?1. Sorveglianza? E come?2. Prevenzione: si o no?2. Prevenzione: si o no?
3. 3. Radiologia o biopsia?Radiologia o biopsia?44. . StagingStaging : : sTCsTC, RMN o , RMN o lipiodollipiodol --TACTAC oo……....5. Resezione, trapianto o trattamento 5. Resezione, trapianto o trattamento
locoregionalelocoregionale ??6. RFA o PEI ?6. RFA o PEI ?7. La Tace 7. La Tace èè utile ?utile ?8. 8. TamoxifeneTamoxifene , , megestrolomegestrolo ,,
octreotideoctreotide , , ……..?..?
Biopsia. Si o no ?
EASL AISF GENE*
All lesions < 2 cm
Se sCT, RMN, US ed AFP
dubbi
Sempre 50%
All doubtful cases
sTC dubbia 18%
For molecular profile and risk
In caso di ter. aggressive 32%
* GRUPPO collaborativo EPATOCARCINOMA NORD-EST
Surveillance and recall strategy for HCC
> 1cm Normal AFPIncreased AFP**
Spiral CTUS/3m
< 1cm
Surveillance US+AFP/6m
AFP > 400 ng/mLCT-MRI-Angiography
FNAB
No HCC
* Available for curative treatments if diagnosed with HCC ** AFP levels to be defined
*** Pathological confirmation or non-invasive criteria
HCC***
< 2cm > 2cm
No noduleLiver nodule
Cirrhotic patients * US+AFP/6m
Bruix et al. J Hepatol 2001
HCC: vascolarizzazione arteriosa
F.P. ???F.N.???
In calo con le nuove tecnologieMacchina-dipendenti !!!Operatore-dipendenti !!!
AlfaFetoproteinaAlfaFetoproteina nellnell’’HCCHCC
0
10
20
30
40
50
<20 ng 20-200 201-400 >401
AFP ng/ml
Distribuzione di 1158 pazienti con HCC per classi di AFPDistribuzione di 1158 pazienti con HCC per classi di AFP
Italica
%
aFPaFP nellnell’’HCCHCC
0
20
40
60
< 2 cm 2-3 cm 3-5 cm >5 cm
AFP >400 ng/ml
Distribuzione di 1158 pazienti per classe di Distribuzione di 1158 pazienti per classe di ChildChild--PughPughe dimensioni del nodulo principalee dimensioni del nodulo principale(risultati (risultati validativalidati in serie interne)in serie interne)
0
20
40
60
1 nodulo 2-3 noduli >3 noduli diffuso massivo
AFP >400 ng/ml
p<0,0001p<0,0001 p<0,0001p<0,0001
%
aFPaFP e sopravvivenza nelle sopravvivenza nell’’HCCHCC
0 30 60 90 1200,00
0,25
0,50
0,75
1,00
Survivor
Times
1
2
3
4
Pazienti non trattati (p<0,0001)
dd
0 50 100 1500,00
0,25
0,50
0,75
1,00
Survivor
Times
1
2
3
4
Pazienti sottoposti a trattamento p <(0,0001)
AFP MEDIANA0-20 ng/ml 12 mesi21-200 ng/ml 13 mesi201-400 ng/ml 10 mesi> 400 ng/ml 5 mesi
AFP MEDIANA 0-20 ng/ml 33 mesi 21-200 ng/ml 26 mesi 201-400 ng/ml 20 mesi > 400 ng/ml 9,2 mesi
Seeding ???
Seeding and biopsy
The risk of seeding appears limited according to the currentl y availableepidemiological data; this should be considered. The be st accuracyin the sampling of hepatocellular carcinoma nodules is o btained bycombining smear cytology and microhistology…… .Seeding………… against the risk of false-positive diagnosis of malignancy based on imaging studies alone.
GUT 2004
Fine-needle biopsy in focal liver lesions: the usefulness of a screening programme and
the role of cytology and microhistology.
When both cytological and microhistological examinations were performed, the positive correlation between the two techniques was 80%, with a slightlyhigher sensitivity for microhistology (93%)
Ital J Gastroenterol. 1995
HCC diagnosis and staging in the 2000s
��Tumor Tumor yesyes //notnot��Tumor Tumor burdenburden��LiverLiver functionfunction��Tumor Tumor biologybiology ??????
New staging systems for HCC: any role for tumor biology ?
0
20
40
60
80
100
12 24 36 48 60
p53 - p53 < 10 p53 > 10
p53 overexpression
Months
%
JIM, 2004
New staging systems for HCC: any role for tumor biology ?
�� CoxCox multiple multiple regressionregression analysisanalysisTNMTNMOkudaOkudaChildChildCD44CD44MIB1 (Ki67)MIB1 (Ki67)GradingGrading
�� p53 single p53 single independentindependent predictorpredictor of of survivalsurvival (p=0.0048)(p=0.0048)
New staging systems for HCC: any role for tumor biology ?
Parameters n Overall survival rates %
1-year 3-year 5-year
P53 expres. - 110 88.8 66.3 60.6
+ 86 83.5 57.3 42.9
++ 13 60.0 46.7
+++ 13 38.5 12.3
Qin LX, W.J.Gastroenterol. 2002
New staging systems for HCC: any role for tumor biology ?
0
20
40
60
80
100
12 24 36 48 60
G1 G2 G3
Grading
Months
%
JIM, 2004
��VascularVascular invasioninvasion and grading and grading determinedetermine outcomeoutcome after after OLTxOLTx forforHCC HCC ……((NeuhausNeuhaus, , HepatologyHepatology2001)2001)
��OLTxOLTx forfor the treatment of the treatment of moderatelymoderately or or wellwell differentiateddifferentiatedHCCHCC…… ((CilloCillo, , AnnAnn SurgerySurgery, 2004), 2004)
Tumor grading ?
Gestione dell’HCC: i problemi1. Sorveglianza? E come?1. Sorveglianza? E come?2. Prevenzione: si o no?2. Prevenzione: si o no?3. 3. Quando Quando biopsiarebiopsiare ..
4. 4. StagingStaging : : sTCsTC, RMN o , RMN o lipiodollipiodol --TACTACoo…….., come esprimerlo?.., come esprimerlo?
5. Resezione, 5. Resezione, OLTxOLTx , , locoregionalelocoregionale ??6. RFA o PEI ?6. RFA o PEI ?7. La Tace 7. La Tace èè utile ?utile ?8. 8. TamoxifeneTamoxifene , , megestrolomegestrolo ,,
octreotideoctreotide , , ……..?..?
Staging
EASL AISF GENEUS + sCT sCT
RMN dinamica(contr.paramagn)
sCT/dRMN 32%Solo sCT 50%
Dynamic MRI>< sCT
USdoppler/colorD
power D/levovist
13% lipiodol CT
No angiography or lipiodol-CT
No angiografia,arterioTC,portoTC
or lipiodol-CT
5% laparoscopia
Classificazione di Barcellona (BCLC)
IPerformance status
Liver Transplantation (CLT / LDLT)
Symptomatic treatment
Okuda 3, PS >2, Child-Pugh C
Terminal stage (D)
Okuda 1-2, PS 0-2, Child-Pugh A-BSTAGES A - C STAGE D
Normal
Locoreg
Curative Treatments50% - 75% at 5 years
Single 3 nodules <3cm
Portal pressure/ bilirubinAssociated
diseasesIncreased
No Yes
Early stage ( A)Single or 3 nodules < 3cm, PS 0
Intermediate stage (B)Multinodular, PS 0
Chemoemb.New
Agents
Advanced stage (C)Extrahep. HCC, PS 1-2
Extrahepatic disease
No Yes
Randomized controlled trials40% - 50% at 3 yr vs 10% at 3yr
Resection PEI/RF
HCC
BCLC Staging and Treatment Strategy
Semin Liver Dis 1999, Hepatology 2002
Survival in untreated HCC
patients
Llovet, Lancet 2003
Life expectancy in untreated earlyHCC
Llovet, Lancet 2003
Intermediate stage HCC ?
14%14%28%28%47%47%J.I.MJ.I.MITALICAITALICA
17%17%27%27%63%63%BCLC IIBCLC II
50%50%65%65%80%80%BCLC IBCLC I
III III yearyearsurvivalsurvival
II II yearyearsurvivalsurvival
I I yearyear
survivalsurvival
CLIP scoring systemScore
Variable 0 1 2
Child-Pugh A B C
Tumormorphology
Uninodular< 50%
Multinodular< 50%
Massive or> 50%
AFP (ng/dL) < 400 ng/dL > 400 ng/dL
Portalthrombosis
No Yes
Add each individual value, score 0 to 6
CLIP score: a new prognostic system
Median Range
CLIP 0 43 37-48 CLIP 1 32 25 – 38 CLIP 2 17 14 - 19 CLIP 3 5 4 – 5 CLIP 4 3 1.5 – 4
CLIP 5-6 1 1 – 1
CLIP group, Hepatology 1998
Survival curves by CLIP staging
0
20
40
60
80
100
12 24 36 48 60
CLIP O CLIP I CLIP 2CLIP 3 CLIP 4 CLIP 5
Farinati, Cancer, 2000
Months
%
BCLC o CLIP?
++--20052005GUTGUTTateishiTateishi
====20032003EJGHEJGHRabeRabe
--++20042004J.HepatJ.HepatCilloCillo
====20042004JIMJIMGianniniGiannini
====20042004DMWDMWCaselitzCaselitz
--++20052005GUTGUTGriecoGrieco
CLIPCLIPBCLCBCLCYearYearJournalJournalAuthorAuthor
TNM forOLTxPTS TNM
15 I
19 II
11 IIIa
13 IVa
2 recurrences, 1 in stage I end1 in stage 3a
Llovet, Hepatology 1998
1)bilobarity2) size of the greatest tumor (2 to 5 cm and > 5 cm)3) vascular invasion(micro/macroscopic). Prognostic risk score (PRS) was calculated
from the relative risks of multivariateanalysis.
Tumor recurrence risk:
grade 1: PRS = 0 to < 7.5;
grade 2: PRS = 7.5 to < or = 11.0;
grade 3: PRS > 11.0 to 15.0;
grade 4: PRS > or = 15.0; and
grade 5: positive node, metastasis, or margin.
Iwatsuki, J.Am.Coll.Surg, 2000
Staging
New staging systems for HCC
�� GroupeGroupe EtudeEtude et et TraitmentTraitment CarcinomeCarcinomeHepatocellulaireHepatocellulaire ::
KarnovskyKarnovsky
BilirubinBilirubinAlkalineAlkaline phosphatasephosphatase 3 3 riskrisk --groupsgroupsAFPAFPPortalPortal thrombosisthrombosis
J. Hepatol, 1999
New staging systems for HCC: the surgical patients
Stage DescriptionStage 1 Single, no vascular invasion
Stage 2 Solitary or multiple,segmental portal thrombosis
Stage 3 Major vessel involved,LN +
Stage 4 Distant metastasis
Izumi, Gastroenterology, 1994Staudacher, Tumori, 2000 ?
Gestione dell’HCC: i problemi
1. Sorveglianza? E come?1. Sorveglianza? E come?2. Prevenzione: si o no?2. Prevenzione: si o no?
3. 3. Quando Quando biopsiarebiopsiare ? Sempre (?)? Sempre (?)4. 4. StagingStaging : : sTCsTC, RMN , RMN CLIP e/o BCLCCLIP e/o BCLC5. Resezione, trapianto o trattamento 5. Resezione, trapianto o trattamento
locoregionalelocoregionale ??6. RFA o PEI ?6. RFA o PEI ?7. La Tace 7. La Tace èè utile ?utile ?8. 8. TamoxifeneTamoxifene , , megestrolomegestrolo ,,
octreotideoctreotide , , ……..?..?
Surveillance and recall strategy for HCC
> 1cm Normal AFPIncreased AFP**
Spiral CTUS/3m
< 1cm
Surveillance US+AFP/6m
AFP > 400 ng/mLCT-MRI-Angiography
FNAB
No HCC
* Available for curative treatments if diagnosed with HCC ** AFP levels to be defined
*** Pathological confirmation or non-invasive criteria
HCC***
< 2cm > 2cm
No noduleLiver nodule
Cirrhotic patients * US+AFP/6m
Bruix et al. J Hepatol 2001
Surveillance and recall strategy for HCC
Any size, any aFP
Treatable Normal AFPIncreased AFP**
Spiral CTCT scan
Large size, untreatable, aFP> 400
Surveillance US+AFP/6m
CT-MRI
FNAB
TREATMENT
Contra for FNAB
No noduleLiver nodule
Cirrhotic patients * US+AFP/6m
Modified from Bruix et al. J Hepatol 2001
HCC
STOP
What about tomorrow ?
Diagnosi-staging-(trattamento)
HCC diagnosis and staging in the 2000s
��Tumor Tumor burdenburden��LiverLiver functionfunction��Tumor Tumor biologybiology
www.gastropadova.itwww.hcc-infohelp.org