Nuove metodiche strumentali inteventistiche e diagnostiche in gastroenterologia

Dr Fabio FarinatiDr Fabio FarinatiGastroenterologia, Gastroenterologia,

PadovaPadova

“Terapie locoregionali percutanee dell’HCC”

Clinical management of HCC: the problems

1. 1. SurveillanceSurveillance2. 2. ChemopreventionChemoprevention3. 3. BiopsyBiopsy : : yesyes or or notnot4. 4. StagingStaging : : imagingimaging and and methodologymethodology5. 5. Treatment of Treatment of earlyearly HCCHCC6. 6. RFA o PEI ?RFA o PEI ?7. 7. IsIs Tace Tace effectiveeffective ??8. 8. TamoxifenTamoxifen , , megestrolmegestrol ,,

octreotideoctreotide , , ……..?..?

“Early” HCC: treatment

Chirurgia Chirurgia 64%64%

PEI/RFA PEI/RFA 30%30%

OLTxOLTx 6%6%

Chirurgia se Chirurgia se a basso a basso rischio rischio

(LFT!).PEI(LFT!).PEI **..

OLTxOLTx <65 <65 aaaaChildChild B/CB/C

SurgerySurgery , , ifif

notnot PEIPEI**..

OltxOltx basedbasedon on availableavailableresourcesresources

Single Single nodenode ,,ChildChild A A (B?)(B?)

SURVEYSURVEYAISFAISF(2001)(2001)

EASLEASL(2000)(2000)

* RFA not validated

Locoregional transparietal Txs

��PEI (PEI (PercutaneousPercutaneous ethanolethanol injectioninjection ))��RadiofrequencyRadiofrequency --mediatedmediated thermalthermal treattreat ..��InterstitialInterstitial laser treatmentlaser treatment��MicrowaveMicrowave treatmenttreatment��IntratumoralIntratumoral chemotherapychemotherapy��IntratumoralIntratumoral immunomodulationimmunomodulation��IntratumoralIntratumoral gene gene therapytherapy

PEI : results

0

20

40

60

80

100

1 2 3 4 5

Curative Palliative Years

Shiina, Cancer 1994

%

Pei versus no treatment

0

20

40

60

80

100

1 2 3

PEI No TxYears

Omata, 1992

Retrospective analysis

%

PEI: Padua experience

0

20

40

60

80

100

1 2 3 4 5

Overall Curative Palliative Years

218 treated patients

%

PEI: tumor size

0

20

40

60

80

100

1 2 3 4 5

<3 cm 3 - 5 cm > 5 cm 2 nodes

p<0.05

%

years

PEI: Child status

0

20

40

60

80

100

1 2 3 4 5

Child A Child B

%

years

p<0.01

PEI: αααα Fetoprotein levels

0

20

40

60

80

100

1 2 3 4 5

< 20 < 50 =/>100

%

Years

p=0.002

PEI versus surgery

0

20

40

60

80

100

1 2 3 4 5

PEI Surgery

%

years

p=n.s.

Castells, Hepatology, 1996

PEI plus TACE : survival

0

20

40

60

80

100

1 2 3 4 5

PEI PEI+TACE

%

years

p=n.s

Nodes < 3 cm

PEI plus TACE : survival

0

20

40

60

80

100

1 2 3 4 5

PEI PEI+TACE

%

years

p<0.05 Nodes > 3 cm

Percutaneous RadioFrequencyInterstitial Thermal Ablation

�� InterstitialInterstitial hyperthermiahyperthermia��MonopolarMonopolar needleneedle , 2 , 2 -- 12 min.12 min.��LimitLimit : : tissuetissue impedanceimpedance��LimitLimit : : largelarge sizesize of the of the needleneedle��LimitLimit : : needneed forfor anesthesiaanesthesia��LimitLimit : 3 cm : 3 cm diameterdiameter of of necrosisnecrosis

RF thermal ablation:developments

�� New New developmentsdevelopments ::–– cold H2Ocold H2O --refrigerated refrigerated needlesneedles ((toto reduce reduce

impedanceimpedance ))–– multiple terminal multiple terminal needleneedle ((toto increaseincrease sizesize of of

necrosisnecrosis ))–– stopstop --flowflow arterialarterial catheterismcatheterism ((toto block block bloodblood --

flowflow thatthat reducesreduces necrosisnecrosis ))

RF thermal ablation

0

20

40

60

80

100

1 2 3 4 5

RFTA

%

Years

Rossi, A.J.R., 1996

RFA or PEI ?

0

20

40

60

80

100

RFA PEI

% Tumoral control

Livraghi, Radiol. 99 Lencioni, Radiol. 99

PEI and RFA: prospective evaluation

0

20

40

60

80

100

1 year2 years

1 year REC2 year REC

PEI RFA

Lencioni, Radiology, 2003

RFA IN EXPLANTED LIVERS

“Early” HCC: RF thermal ablation

�� EASL = EASL = promisingpromising , , similarsimilar or or eveneven betterbetterresponseresponse rate, rate, fewerfewer sessionssessions , , higherhigher rate rate of side of side effectseffects , , lowerlower applicabilityapplicability

�� AISF = the AISF = the locoregionallocoregional treatment of treatment of choicechoice isis PEIPEI

Forget about ethanol !!!

Barcelona, EASL, AGA, JCSJune 2005

ETOH

Forget about ethanol !!!

Barcelona, EASL, AGA, JCSJune 2005

ETOH

PEI is…• Less efficient• More time consuming• Similar costs (JPN)

RFA has…• Very high applicability (?)• Few complications

HOWEVER…..

Barcelona, EASL, AGA, JCSJune 2005

ETOH

ETOH < 2 cmDifficult position

RFA < 3 CM> 3 = SURGERY

Why 3 cm ???

> 3 cm

1 cm cancer-freemargin (as in surg.)

“Our” data

COMPLICANCE (34% pts)EC immediati (11%)

% EC ricovero (22%)

% EC post-ricovero(7%)

%

Dolore 42 Febbre 45 Febbre 38

Spasmo diaframmatico

19 Dolore 37 Ascite 23

Conati di vomito 19 Ascite 6 Fistola 15

Pneumotorace 4 Colica biliare 4 Ascesso 7

Pneumoperitoneo 4 Ematoma 2 Dolore 7

Extrasistolia 4 Emobilia 2 7

Stillicidio ematico 4 2Morte-Ictus

Morte-perfor. intest

MortalityMortality: 0,5%: 0,5%

Seeding 0.8%

RFA: caveats !!!

�� RapidRapid progressionprogression of HCC after RFAof HCC after RFA�� RuzzenenteRuzzenente etet al.al.�� World Journal of World Journal of GastroenterologyGastroenterology , 2004, 2004

4/87 patients (5%), with lesions proximalto major portal branches or with elevated AFP

Unexpected and rapid HCC progression

Dopo RFA, rapida progressione non clinicamente o biologicamente plausibile. 11 casi /359 (3%) pazienti nel nostro studio

# localizzazioni MULTIPLE anche di nodi di dimensioni rilevanti a 1-6 mesi dal trattamento# 1 paziente metastatizzazione polmonare massiva con malattia epatica trattata

MECHANISMS ?

vaporizzazione della massa tumorale

T°C

ESPLOSIONE ESPLOSIONE DISSEMINAZIONEDISSEMINAZIONE

TGFTGFββββββββ11

LBFLBF --GFGFCRESCITA CRESCITA

TUMORALETUMORALE

Ohno T et al, J.Hepatol., 2002

TAC dopo 1 mese dalla RFTA

Residuo di malattia

TAC dopo 4 mesi, multiple lesioni

nodulari bilobari

M.M.

a. 73

TAC torace: quadro

plurimetastatico a livello polmonare

TAC (12 mesi) HCC trattato con

successo

C.V.

a 50

RFA

• Large scale study

• Long time observation

• End of honey-moon effect

Surgery OLTx

RFA/PEI