hcc ressecção x tx
TRANSCRIPT
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SERVIÇO DE TRANSPLANTES DO APARELHO DIGESTIVO
HC-FMUSP
Dr. André Ibrahim David
Dr. Rafael A. A. Pécora
Dr. Paulo Hermann
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IMPORTÂNCIA
Sexto câncer mais comum
Aumento da incidência: 4,9/100.000 pessoas ao ano nos EUA
Terceira causa de morte por câncer
Parkin DM et al. Global Cancer Statistic, 2002. CA Cancer J Clin. 2005
Altekruse SF et al. J Clin Oncol. 2009
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Por que a incidência do
Carcinoma Hepatocelular continua a aumentar ?
1 – Melhor triagem
2 – Infecção epidêmica de VHC
3 – Epidemia de obesidade
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Infecção por VHC
Morte por cirrose ou HCC
0
5
10
15
20
Incid
ên
cia
(po
r 1
00
.00
0)
Idade (anos)
1982 - 19841991 - 19932000 - 2002
Incidência do CHC nos EUA
Infecção pelo VHC
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Source : National Center for Health Statistics
Relative Risk of Liver Cancer
BMI< 25 25-30 30-35 >35
Men 1.00 1.13 1.90 4.52
Women 1.00 1.02 1.40 1.68
New Engl J Med (2003) 900.000 adults, USABr J Cancer (2005) 145.00 adults, Australia
Epidemia de obesidade
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Racional do Tratamento
Cirurgia: sobrevida de 39% em 5 anos
Aumento do tratamento cirúrgico : 28%(92-93) → 44% (03/04)
Diagnóstico precoce (rastreamento dos grupos de risco)
Nathan H et al. Ann Surg. 2009
Altekruse SF et al. J Clin Oncol. 2009
Evolução da cirurgia hepática → ressecção em cirróticos
Fong Y et al. Ann Surg. 1999
Sobrevida ruim: 13% em 5 anos
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Desenvolvimento de novas terapias nos últimos 15 anos
Indicação bem aceita para Transplante Hepático (Critérios de Milão, 1996)
Jarnagin W et al. HPB (Oxford). 2010
Mazzafero V et al. N Engl J Med .1996
Racional do Tratamento
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Cancer. 2011
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Cancer. 2011
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• 29 centros participantes
• 1405 pacientes incluídos
• Idade média: 59 anos
• Sexo– Masculino: 78%– Feminino: 22%
Inquérito Nacional do Carcinoma Hepatocelular- SBH/ Luciana Kikuchi, 2010
Inquérito Nacional do CHC
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Inquérito Nacional do Carcinoma Hepatocelular- SBH/ Luciana Kikuchi, 2010
Inquérito Nacional do CHC
Child-Pugh
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Distribuição dos pacientes de
acordo com 1° tratamento
Inquérito Nacional do Carcinoma Hepatocelular- SBH/ Luciana Kikuchi, 2010Inquérito Nacional do Carcinoma Hepatocelular- SBH/ Luciana Kikuchi, 2010
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Opções de tratamento
Ressecção
Transplante
Terapias ablativas
Quimioembolização
Quimioterapia sistêmica
Estadiamento
X
Função hepática
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Opções de tratamento
Ressecção
Transplante
Terapias ablativas
Quimioembolização
Quimioterapia sistêmica
Estadiamento
X
Função hepática
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Ressecção
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Ressecção
Margens adequadas → remoção micrometástases → evitar recidiva
Preservação parênquima → sobreviver à cirurgia
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Abordagem pré-operatória
TC/RM: diagnóstico, estadiamento, ressecabilidade, extensão da hepatectomia e doença hepática crônica
Reserva funcional
- CHILD-PUGH (A/B)
- MELD
- Hipertensão portal
- Biópsia
- Verde Indocianina
Volumetria (40-50% nos cirróticos)
Embolização portal
Belghiti J et al. HPB 2005
Fan ST et al. J Hepatobiliary Pancreat Surg Sci 2010
Manizate F et al. J Hepatobiliary Pancreat Surg Sci 2010
Kishi Y et al. Ann Surg 2009
Schindl MJ et al. Gut 2005
Quimioembolização do tumor
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“Liver function assessment was based largely on the results of the
indocyanine green (ICG) clearance test. An ICG retention rate of 14%
at 15 minutes after intravenous injection was acceptable for major
hepatectomy. For minor hepatectomy, the cut-off value was 22%”
Fan ST et al, Ann Surg 2011
Verde de Indocianina
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Reserva Funcional
Ressecção
- CHILD-PUGH A
- Bilirrubina ≤ 1mg/dL
- Hipertensão portal (plq >100.000 /µL, GVH < 10mmHg, Varizes –
- Verde Indocianina não utilizado
Manizate F et al. J Hepatobiliary Pancreat Surg Sci 2010
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Aumento do volume residual→ resgate irressecáveis
Avaliar capacidade regeneração
750 cc
1015 cc
Embolização Portal
Ogata S et al. Br J Surg 2006
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750 cc
1015 cc
Medidas intra-operatórias
Man K et al. Ann Surg 1997
Clavian PA et al. Ann Surg 2003
Imamura H et al. Lancet 2002
Belghiti J et al. Ann Surg 1996
USG intra-operatório
Preservação hepática:
- Oclusão vascular: hemi ou Pringle (↓sangramento)
- Pré-condicionamento (10 min)
- Oclusão intermitente
- Associação
- Evitar exclusão vascular total
Técnica de secção do parenquima
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Ressecção x Função
Melhores candidatos à ressecção: - CHC único
- Child-Pugh A: Ausência de HP
Bilirrubina normal
0
20
40
60
80
100
0 12 24 36 48 60 72 84 96
Sem hipertensão portal (n= 35)
Hipertensão portal e bilirrubina normal (n=15)
Hipertensão portal e bilirrubina >1 mg/dL (n=27)
Log Rank 0,00001
Sobre
vid
a (
%)
meses
74%
50%
25%
Llovet et al. Hepatology, 1999
n=77
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Shimozawa, J Am Coll Surg, 2004
135 ressecções CHC < 3cm
Morbidade 25% e mortalidade 2%
Impacto da Cirrose
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Takayama T, Jpn J
Clin Oncol 2011
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Takayama T et al. Jpn J Clin Oncol 2011
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Takayama T et al. Jpn J Clin Oncol 2011
Mediana:
• 1ano – 80%
• 3 anos – 70%
• 5 anos – 50%
Ressecção
Recorrência :
• 5 anos – 77 a 100 %
• Fígado – 80%
• Ressecáveis – 20%
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Ressecção
Annals of Surgery 2007
1 cm x 2 cm
n=169
Livre de doença Global
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Ressecção
Surgery 2010
GlobalLivre de doença
≤ 5 cm
n=373
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Ressecção
Multinodular
Invasão
macrcópica
J Gastrointest Surg 2009
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Aspectos e princípios técnicos
Annals of Surgery. 2011
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Aspectos e princípios técnicos
Anatômica X Não Anatômica
Annals of Surgery. 2011
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Aspectos e princípios técnicos
Linfadenectomia
Annals of Surgery. 2011
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Aspectos e princípios técnicos
Ressecções vasculares
Annals of Surgery. 2011
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Aspectos e princípios técnicos
Annals of Surgery. 2011
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Fatores Prognósticos
Livre de doença Global
Idade ≥ 60 a 0,040 CHILD B 0,0009
CHILD B 0,039 Cirrose 0,0027
Albumina < 3,5 0,086 Albumina 0,0028
ICGR -15(%) < 20 0,044 ICGR -15(%) < 20 0,0023
Análise Univariada
Shimozawa, J Am Coll Surg, 2004
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Poon R, Ann Surg 1999
Tratamento da Recidiva
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Transplante
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Transplante
Remove o tumor – margem
Metástases intrahepáticas
Remove a cirrose de base - Tu ‘de novo’
Child e MELD
Melhor sobrevida a longo prazo
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Escassez de órgãos
Critérios restritivos N e T
Tempo de espera e drop out
Problemas de imunossupressão e recidiva
Transplante
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0
200
400
600
800
1000
1200Número de pacientes em lista de espera
Número de transplantes realizados
Limitação de Órgãos
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Drop out: 15-33%
Llovet et al. Hepatology 1998
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TRANSPLANTE NO CHC
Maior ou igual a 2cm
Sem indicação de ressecção
Dentro dos critérios de Milão
Complicação de doença hepática crônica
Ausência de invasão vascular
Diagnóstico: critérios de Barcelona
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IRRESSECABILIDADE
MELD > 10
CHILD-PUGH B ou C
Na+ < 135
Ressecções de dois ou mais segmentos
Tumores múltiplos (mais de 1 nódulo em segmentos distintos)
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SITUAÇÃO ESPECIAL
MELD 20 3 meses MELD 24
CHC
MELD baixoTRANSPLANTE
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TRANSPLANTE NO CHC
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Mazzaferro et al. NEJM 1996
MILAN CRITERIA
• 1 nodule, < 5 cm
• < 3 nodules, < 3cm
• No macroscopic vascular invasion
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Transplante Hepático para CHC
Resultados com os Critérios Restritivos
Autores N Critérios de Seleção Rec Survival 5a
* Sobrevida 5a
Mazzaferro, NEJM 1996 48 Único < 5cm 8% 74%*
3 nódulos < 3cm
Bismuth, Semin Liver Dis 1999 45 Único < 3cm 11% 74%
3 nódulos < 3cm
Llovet, Hepatology 1999 79 Único < 5cm 4% 75%
Jonas, Hepatology 2001 120 Único < 5cm 16% 71%
3 nódulos < 3cm
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Takayama T et al. Jpn J Clin Oncol 2011
Transplante Hepático para CHC
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RESSECÇÃO VERSUS TRANSPLANTE
Indicação Cirúrgica no CHC
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Is resection an appropriate treatment for HCC?
Hepatocellular Carcinoma
Effective Treatments
• Resection
• Liver Transplantation
How to choose ?
No RCT
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Single Small Nodule + Good Liver Function + No Portal Hypertension
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20-30% 5y GS
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Chan et al. Ann Surg 2008
Survival according to treatment modality
Hepatocellular Carcinoma
0 20 40 60 80 100 120
0%
20%
40%
60%
80%
100%
Resection
Liver Transplantation
Radiofrequency
TACEConservative
Months
Su
rviv
al
(%)
Treament
of the cancer
and
liver disease
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Preserved liver function
Organ shortage
Progression in the waiting list
LT higher morbidity and mortality
Less expensive
Can be readily performed
Independent from age; tumor size or vein invasion
Independent of graft availability
Poon & Fan, 2004; Llovet et al., 2004
HCC: Liver Resection
Rationale
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Transplantation for HCC –
Intention to treat
Pelletier S et al, Liver Transpl 2009
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Post-Transplant
Resection
Transplantation for HCC –
Intention to treat
Resection
=
LT
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Fan et al, Br J Surg 2011
Patients CHILD-PUGH A within Milan Criteria
Liver Resection of HCC
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RESULTS
• Similar results than LT intention to treat or for
Child A and within Milan
• However = higher recurrence rate
HCC: Liver Resection
BUT = more effective treatment for small recurrence is
more effective in resected patients than in transplanted
ones (re-resection; ablation; salvage LT)
Fan et al, Br J Surg 2011
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Cherqui et al, Ann Surg 2009
Liver Resection for transpantable HCC
67 LLR (tumors within Milan)
Mortality = 4.5%
56% recurred (77% transplantable)
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Liver resection before LT should be
considered in the treatment of HCC
•70 Primary OLT
•18 Secondary OLT (salvage)
after liver resection
Ann Surg, 2003
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42%
51%
62%
41%
52%
Liver Resection – 5y Survival
Fong, 1999 (100)
Llovet, 1999 (77)
Takayama, 2000 (74)
Wayne, 2002 (249)
Lee, 2010 (130)
Hepatocellular Carcinoma
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Time (months)
Dis
ease F
ree S
urv
ival (%
)
0
20
40
60
80
100
0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180
80 %
54 %
36 %
33 %
Survival120 pacients resected
HCFMUSP
Mortality = 5.3%
5y GS = 63.6%
5y DFS = 36.3%
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25
HCC Resection - Morbidity
21
1312
8
6
0
5
10
15
20 ASCITE
INSUF HEPÁTICA
DERRAME PLEURAL
ABSCESSO PAREDE
SEPSIS
Global – 36.5 %
HCFMUSP
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Mortality – 400 liver resections
0 5 10
Intrahepatic
Lithiasis
Benign tumors
HCC – 93 casos
Metastasis
0 %
0 %
5.3 %
1.1 %
HCFMUSP
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J Am Coll Surg 2010
OS
DFS
163 cases (3 centers)
Anatomic resection = 65%
Mortality= 1.2%; Morbidity= 22%
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Belli et al, Br J Surg 2009
HCC: Laparoscopic X Open Resection
7% of conversion2% of mortality
54 LLR X 125 OR
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HCC: Laparoscopic Liver Resection
Advantages
No collateral vessels ligation = Less ascitis
Less bleeding
Fewer postoperative adhesions
Salvage transplantation possible (easier transplant)
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HCC: Laparoscopic Liver Resection
PATIENT SELECTION
Peripheral (anterior or lateral segments - 2,3,4b,5,6)
Solitary nodule
Smaller than 5cm (unless LLS or pedunculated)
CHILD A patients
Absence or mild portal hypertension (Grade 1
varices; platelet count > 100.000)HCFMUSP
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Indications (n = 105)
• Liver cell adenoma = 36
• Coloretal metastasis = 28
• HCC = 22
• FNH = 4
• Biliary cystoadenoma = 3
• Breast Ca metastasis = 2
• Intrahepatic lithiasis = 3
• Melanoma metastasis = 2
• Peripheric cholangioCa = 1
• Hemangioendothelioma = 1
• Liver fibroma = 1
• HCC Fibrolamellar = 1
• Angiomyolipoma = 1
Laparoscopic Liver Resection
University of São Paulo Experience
HCFMUSP
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HCC = 22• Nodulectomy = 9
• Bi-segmentectomy 2+3 = 4
• Segmentectomy 6 = 4
• Bi-segmentectomy 6+7 = 2
• Right hepatectomy = 2
• Left hepatectomy = 1
Results• Morbidity = 3 (13.6%)
Ascitis = 1
Sepsis (pneumonia) = 1
Subphrenic abscess= 1
• Mortality = 0
Laparoscopic Liver Resection
13 (59%) anatomic resections
HCFMUSP
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Hepatocellular CarcinomaTreatment Algorithm – CHILD A Patients
Centrally located small (<2cm) HCC
Solitary nodule
Peripheral, small (<5cm) HCC
Solitary nodule
Centrally located (>2cm) HCC
Solitary nodule
Large solitary nodule
LLR
RFA
Open resection;
TACE
Open resection +
PVE
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Ressecção x TransplanteDentro dos Critérios de Milão
Poon RT, Ann Surg 2007
Invasão vascular microscópica -
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Ressecção x TransplanteAlém dos Critérios de Milão
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Lee et al, J Surg Onc, 2010
Ressecção x TransplanteAlém dos Critérios de Milão
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Adam R et al. Ann Surg 2003
Ressecção antes do transplante
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OLT after liver resection doesn’t significantly increase the technical difficulty
of the surgery or impair survival after OLT
Liver resection before LT should be considered in the treatment of HCC.
70 Primary OLT 18 Secondary OLT after liver resection
11 Recurrence4 Deterioration of liver function3 Incomplete prior resection
( + margin or satellite nodules)
Ann Surg 2003
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Cherqui et al. Annals of Surgery 2009
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Cherqui et al. Annals of Surgery 2009
Sobrevida
Risco recorrência
Transplante secundário
Data do TX
Data Hepatectomia
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Takayama T, Jpn J Clin Oncol 2011
Ressecção x Ablação
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Chan ACY et al. Ann Surg 2008
Sobrevida de acordo com a modalidade de tratamento
0 20 40 60 80 100 120
0%
20%
40%
60%
80%
100%
Ressecção
Transplante Hepático
Radiofreqüência
QuimioembolizaçãoConservador
Meses
So
bre
vid
a (
%)
Tratamento do Carcinoma Hepatocelular
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Opções terapêuticas em casos selecionados
A limitação é a função, e não o N ou T
Devemos melhorar nossa seleção
Tx Intervivos
No Brasil a lei desfavorece a ressecção
A re-ressecção ou o transplante de resgate são opções nas recidivas
Conclusões
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OBRIGADO !
“Ainda que busquemos critérios científicos e
objetivos para a indicação adequada no tratamento
cirúrgico do CHC, nesta patologia, o bom
senso, será sempre decisivo”
Jacques Belghiti-2005