HCC ressecção X tx

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  • 1. SERVIO DE TRANSPLANTES DO APARELHO DIGESTIVO HC-FMUSP Dr. Andr Ibrahim David Dr. Rafael A. A. Pcora Dr. Paulo Hermann

2. IMPORTNCIA Sexto cncer mais comum Aumento da incidncia: 4,9/100.000 pessoas ao ano nos EUA Terceira causa de morte por cncer Parkin DM et al. Global Cancer Statistic, 2002. CA Cancer J Clin. 2005 Altekruse SF et al. J Clin Oncol. 2009 3. Por que a incidncia do Carcinoma Hepatocelular continua a aumentar ? 1 Melhor triagem 2 Infeco epidmica de VHC 3 Epidemia de obesidade 4. Infeco por VHC Morte por cirrose ou HCC 0 5 10 15 20 Incidncia(por100.000) Idade (anos) 1982 - 1984 1991 - 1993 2000 - 2002 Incidncia do CHC nos EUA Infeco pelo VHC 5. 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, USA Br J Cancer (2005) 145.00 adults, Australia Epidemia de obesidade 6. Racional do Tratamento Cirurgia: sobrevida de 39% em 5 anos Aumento do tratamento cirrgico : 28%(92-93) 44% (03/04) Diagnstico precoce (rastreamento dos grupos de risco) Nathan H et al. Ann Surg. 2009 Altekruse SF et al. J Clin Oncol. 2009 Evoluo da cirurgia heptica resseco em cirrticos Fong Y et al. Ann Surg. 1999 Sobrevida ruim: 13% em 5 anos 7. Desenvolvimento de novas terapias nos ltimos 15 anos Indicao bem aceita para Transplante Heptico (Critrios de Milo, 1996) Jarnagin W et al. HPB (Oxford). 2010 Mazzafero V et al. N Engl J Med .1996 Racional do Tratamento 8. Cancer. 2011 9. Cancer. 2011 10. 29 centros participantes 1405 pacientes includos Idade mdia: 59 anos Sexo Masculino: 78% Feminino: 22% Inqurito Nacional do Carcinoma Hepatocelular- SBH/ Luciana Kikuchi, 2010 Inqurito Nacional do CHC 11. Inqurito Nacional do Carcinoma Hepatocelular- SBH/ Luciana Kikuchi, 2010 Inqurito Nacional do CHC Child-Pugh 12. Distribuio dos pacientes de acordo com 1 tratamento Inqurito Nacional do Carcinoma Hepatocelular- SBH/ Luciana Kikuchi, 2010Inqurito Nacional do Carcinoma Hepatocelular- SBH/ Luciana Kikuchi, 2010 13. Opes de tratamento Resseco Transplante Terapias ablativas Quimioembolizao Quimioterapia sistmica Estadiamento X Funo heptica 14. Opes de tratamento Resseco Transplante Terapias ablativas Quimioembolizao Quimioterapia sistmica Estadiamento X Funo heptica 15. Resseco 16. Resseco Margens adequadas remoo micrometstases evitar recidiva Preservao parnquima sobreviver cirurgia 17. Abordagem pr-operatria TC/RM: diagnstico, estadiamento, ressecabilidade, extenso da hepatectomia e doena heptica crnica Reserva funcional - CHILD-PUGH (A/B) - MELD - Hipertenso portal - Bipsia - Verde Indocianina Volumetria (40-50% nos cirrticos) Embolizao 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 Quimioembolizao do tumor 18. 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 19. Reserva Funcional Resseco - CHILD-PUGH A - Bilirrubina 1mg/dL - Hipertenso portal (plq >100.000 /L, GVH < 10mmHg, Varizes - Verde Indocianina no utilizado Manizate F et al. J Hepatobiliary Pancreat Surg Sci 2010 20. Aumento do volume residual resgate irressecveis Avaliar capacidade regenerao 750 cc 1015 cc Embolizao Portal Ogata S et al. Br J Surg 2006 21. 750 cc 1015 cc Medidas intra-operatrias 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-operatrio Preservao heptica: - Ocluso vascular: hemi ou Pringle (sangramento) - Pr-condicionamento (10 min) - Ocluso intermitente - Associao - Evitar excluso vascular total Tcnica de seco do parenquima 22. Resseco x Funo Melhores candidatos resseco: - CHC nico - Child-Pugh A: Ausncia de HP Bilirrubina normal 0 20 40 60 80 100 0 12 24 36 48 60 72 84 96 Sem hipertenso portal (n= 35) Hipertenso portal e bilirrubina normal (n=15) Hipertenso portal e bilirrubina >1 mg/dL (n=27) Log Rank 0,00001 Sobrevida(%) meses 74% 50% 25% Llovet et al. Hepatology, 1999 n=77 23. Shimozawa, J Am Coll Surg, 2004 135 resseces CHC < 3cm Morbidade 25% e mortalidade 2% Impacto da Cirrose 24. Takayama T, Jpn J Clin Oncol 2011 25. Takayama T et al. Jpn J Clin Oncol 2011 26. Takayama T et al. Jpn J Clin Oncol 2011 Mediana: 1ano 80% 3 anos 70% 5 anos 50% Resseco Recorrncia : 5 anos 77 a 100 % Fgado 80% Ressecveis 20% 27. Resseco Annals of Surgery 2007 1 cm x 2 cm n=169 Livre de doena Global 28. Resseco Surgery 2010 GlobalLivre de doena 5 cm n=373 29. Resseco Multinodular Invaso macrcpica J Gastrointest Surg 2009 30. Aspectos e princpios tcnicos Annals of Surgery. 2011 31. Aspectos e princpios tcnicos Anatmica X No Anatmica Annals of Surgery. 2011 32. Aspectos e princpios tcnicos Linfadenectomia Annals of Surgery. 2011 33. Aspectos e princpios tcnicos Resseces vasculares Annals of Surgery. 2011 34. Aspectos e princpios tcnicos Annals of Surgery. 2011 35. Fatores Prognsticos Livre de doena 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 Anlise Univariada Shimozawa, J Am Coll Surg, 2004 36. Poon R, Ann Surg 1999 Tratamento da Recidiva 37. Transplante 38. Transplante Remove o tumor margem Metstases intrahepticas Remove a cirrose de base - Tu de novo Child e MELD Melhor sobrevida a longo prazo 39. Escassez de rgos Critrios restritivos N e T Tempo de espera e drop out Problemas de imunossupresso e recidiva Transplante 40. 0 200 400 600 800 1000 1200 Nmero de pacientes em lista de espera Nmero de transplantes realizados Limitao de rgos 41. Drop out: 15-33% Llovet et al. Hepatology 1998 42. TRANSPLANTE NO CHC Maior ou igual a 2cm Sem indicao de resseco Dentro dos critrios de Milo Complicao de doena heptica crnica Ausncia de invaso vascular Diagnstico: critrios de Barcelona 43. IRRESSECABILIDADE MELD > 10 CHILD-PUGH B ou C Na+ < 135 Resseces de dois ou mais segmentos Tumores mltiplos (mais de 1 ndulo em segmentos distintos) 44. SITUAO ESPECIAL MELD 20 3 meses MELD 24 CHC MELD baixo TRANSPLANTE 45. TRANSPLANTE NO CHC 46. Mazzaferro et al. NEJM 1996 MILAN CRITERIA 1 nodule, < 5 cm < 3 nodules, < 3cm No macroscopic vascular invasion 47. Transplante Heptico para CHC Resultados com os Critrios Restritivos Autores N Critrios de Seleo Rec Survival 5a * Sobrevida 5a Mazzaferro, NEJM 1996 48 nico < 5cm 8% 74%* 3 ndulos < 3cm Bismuth, Semin Liver Dis 1999 45 nico < 3cm 11% 74% 3 ndulos < 3cm Llovet, Hepatology 1999 79 nico < 5cm 4% 75% Jonas, Hepatology 2001 120 nico < 5cm 16% 71% 3 ndulos < 3cm 48. Takayama T et al. Jpn J Clin Oncol 2011 Transplante Heptico para CHC 49. RESSECO VERSUS TRANSPLANTE Indicao Cirrgica no CHC 50. Is resection an appropriate treatment for HCC? Hepatocellular Carcinoma Effective Treatments Resection Liver Transplantation How to choose ? No RCT 51. Single Small Nodule + Good Liver Function + No Portal Hypertension 52. 20-30% 5y GS 53. 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 TACE Conservative Months Survival(%) Treament of the cancer and liver disease 54. 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 55. Transplantation for HCC Intention to treat Pelletier S et al, Liver Transpl 2009 56. Post-Transplant Resection Transplantation for HCC Intention to treat Resection = LT 57. Fan et al, Br J Surg 2011 Patients CHILD-PUGH A within Milan Criteria Liver Resection of HCC 58. 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 59. Cherqui et al, Ann Surg 2009 Liver Resection for transpantable HCC 67 LLR (tumors within Milan) Mortality = 4.5% 56% recurred (77% transplantable) 60. 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 61. 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 62. Time (months) DiseaseFreeSurvival(%) 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 % Survival 120 pacients resected HCFMUSP Mortality = 5.3% 5y GS = 63.6% 5y DFS = 36.3% 63. 25 HCC Resection - Morbidity 21 13 12 8 6 0 5 10 15 20 ASCITE INSUF HEPTICA DERRAME PLEURAL ABSCESSO PAREDE SEPSIS Global 36.5 % HCFMUSP 64. Mortality 400 liver resections 0 5 10 Intrahepatic Lithiasis Benign tumors HCC 93 casos Metastasis 0 % 0 % 5.3 % 1.1 % HCFMUSP 65. J Am Coll Surg 2010 OS DFS 163 cases (3 centers) Anatomic resection = 65% Mortality= 1.2%; Morbidity= 22% 66. Belli et al, Br J Surg 2009 HCC: Laparoscopic X Open Resection 7% of conversion 2% of mortality 54 LLR X 125 OR 67. HCC: Laparoscopic Liver Resection Advantages No collateral vessels ligation = Less ascitis