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Hepatocellular Carcinoma Diagnostic and Therapeutic Strategies

Hepatocellular Carcinoma Diagnostic and Therapeutic Strategies. Faisal Sanai Consultant Hepatologist Riyadh Military Hospital. 10 th International Advanced Medicine Symposium. Tumor Markers for HCC.  -l-Fucosidase. 5’- nucleotide phosphodiesterase. Des 3  carboxy prothrombin.

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Hepatocellular Carcinoma Diagnostic and Therapeutic Strategies

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  1. Hepatocellular CarcinomaDiagnostic and Therapeutic Strategies Faisal Sanai Consultant Hepatologist Riyadh Military Hospital 10th International Advanced Medicine Symposium

  2. Tumor Markers for HCC • -l-Fucosidase. • 5’- nucleotide phosphodiesterase. • Des3 carboxy prothrombin. • CA 19-9, CA 125, ALP. • Alpha Fetoprotein. • Fucosylated AFP.

  3. GI tumors: 10 – 20%. Cirrhosis: 40%. Acute and chronic hepatitis: 20%. Pregnancy. Gonadal tumors: 80%. Ethnicity. Etiology of liver disease. Treatment of underlying liver disease. Tumor staging. Alpha FetoproteinSensitivity and Specificity Issues • Sensitivity patterns for HCC vary widely: 32 – 93% • Colli A, et al. Am J Gastro 2006.

  4. Alpha FetoproteinChange in HCC Detection by Changing Cut-off Points Poon TCW, Clin Liv Dis 2001

  5. Diagnostic Yield of U/S • Sensitivity in cirrhotic liver: 60%. • Specificity: 97%. Colli A, et al. Am J Gastro 2006 • Sensitivity for lesions 1 - 2 cm: 13%. • Sensitivity for lesions 2 - 3 cm: 20%. Dodd G, et al. AJR 1992

  6. CT Scan for HCC Diagnosis • Diagnostic procedure of choice. • Arterial phase CT is vastly superior to double phase scanning. • The sensitivity of CT is much greater than ultrasonography (80% vs 60%). Chalasani N, et al. Am J Gastro 1999

  7. The CT Modality of Choice • Recent lipiodol studies have shown reduced sensitivities compared to initial reports. • Reduced sensitivity compared to triple phase CT. Ngan H. Br J Radiol 1990 Nakayama A, et al. Ann Surg 2001

  8. AngiographyDoes the Route Make Any Difference ? • 109 patients with HCC. • Sensitivity of angiographic interventions studied. • CT Lipoidol – 80%. • CT Portography – 84.4%. • CT Angiography – 91.3%. • CT portography revealed additional 15% lesions that had significant therapeutic alterations. Malagari K & Hadziyannis S. Hepatogastroenterology 1999

  9. To Biopsy or Not to Biopsy… • Pre-existing cirrhosis + mass >2 cm: • >95% chance of HCC. • Pre-existing cirrhosis + mass <2 cm: • ≈ 75% chance of HCC. Frazer C J Gastro & Hepat 1999 Horigome H, et al J Gastro & Hepatol 1999 • “Only where considerable doubt exists, will a biopsy of the lesion be required.” • BSG Guidelines – Ryder SD, Gut 2003.

  10. Needle Track Seeding • Incidence of 1 - 2% for each biopsy attempt. • Incidence lower with FNA than tru-cut. • Needle track seeding converts curative resection to palliative. • False-positive clinical/radiological diagnosis about 3%. • 20% in HCC <3cm and low AFP Levy I, et al. Ann Surg 2001

  11. BiopsyThe Guidelines • Lesions <1 cm should not be biopsied. • Lesions 1 - 2 cm should have FNA + biopsy. Conclusions of EASL 2000, J Hepatol 2001 Bruix J, et al. AASLD Guidelines 2005 • Lesions >2 cm should not be biopsied in presence of diagnostic clinical criteria. Conclusions of EASL 2000, J Hepatol 2001 Abdo A, et al. Saudi Guidelines for HCC, Ann Saudi Med 2006 Bruix J, et al. AASLD Guidelines 2005

  12. Setting Diagnostic Criteria • Histological diagnosis. • Presence of classic appearance in one imaging modality + AFP >400 µg/L + appropriate clinical setting. • Presence of normal AFP + classic (>2 cm nodule, arterial vascularity) appearance in two imaging modalities + appropriate clinical setting. Saudi Guidelines for HCC, Ann Saudi Med 2006 Conclusions of EASL 2000, J Hepatol 2001

  13. Surveillance and Recall Strategy for HCC Cirrhotic patients (US + AFP/6 m) Liver nodule No nodule 1 cm <1 cm Increased AFP* Normal AFP <2 cm >2 cm US/3m Spiral CT FNAB AFP 400 ng/mL CT/MRI/Angiography No HCC HCC** Surveillance US + AFP/6 m *AFP levels to be defined; **Pathological confirmation or non-invasive criteria

  14. Decision making in HCC Treatment • The status of the non-tumorous liver: • Underlying cirrhosis. • Non-cirrhotic liver (HBV). • Size and extension of the tumour: • Is it ≤5 cm in size/≤3 lesions ≤ 3 cm ? • Vascular involvement. • General condition of patient, the age and expected life expectancy.

  15. Liver Transplantation for HCC • HCC is the curative intervention of choice • Survival: 75% at 5 years. • Data comparable to non-HCC LT. • HCC require priority listing for LT. • Living Donor LT can be offered. • Milan Criteria serve as threshold for LT option (single lesion < 5 cm; ≤ 3 in number, < 3 cm). Conclusions of EASL 2000, J Hepatol 2001 Saudi Guidelines for HCC, Ann Saudi Med 2006 Bruix J, et al. AASLD Guidelines 2005

  16. Liver Transplantation for HCCExpanding the Milan Criteria UCSF Criteria:(single lesion < 6.5 cm; ≤ 3 in number, < 4.5 cm; combined diameter < 8cm) Survival Yao et al. Hepatology 2005, 197A

  17. The Optimal Resection Candidate • All non-cirrhotic patients with no extrahepatic spread (Western 5%, Asian 40%). • When cirrhosis present - 30%: • Child-Pugh class ‘A’. • No portal HTN. • Pr. gradient >10 mmHg • Oesophageal varices • Splenomegaly  plats <105 • Patient is not a candidate for LT treatment. • Solitary lesions <5 cm.

  18. ResectionsOutcome • Recurrence: • 5 years >70%. • Survival: • 3 years: 38 - 65%. • 5 years: 33 - 44%. • Decompensation: • 50%. Song TJ, et al. Gastroenterology 2004

  19. Local Ablative Therapies for HCCPEI: Livraghi T, et al., J Hepatol 1995 Survival: 3 years, 391 patients, 1 lesion, <5 cm

  20. Local Ablative Therapies for HCC • Radiofrequency Ablation (Lencioni R et al, Radiology 2003) • Randomized trial: RFA vs PEI. • Child A or B in accordance with Milan criteria. Buscarini L et al., Eur Radiol 2001

  21. Rationale for Embolization Therapy • HCC blood supply >90% from hepatic artery. • Normal liver 70 - 80% blood supply from portal vein. Breedis et al, Am J Pathol 1954 • Occlusion of blood supply may cause tumor necrosis in up to 95% of lesion. Higuchi et al, Cancer 1994

  22. Improved Survival with TACE • Systematic review of 7 RCT comprising 545 patients. Llovet & Bruix, Hepatology 2003 • (Chemo)embolization vs no treatment. • Significant improvement in 2 year survival. • Subanalysis showed significant benefit with chemoembolization but not with bland emolization. • Small tumors, good liver reserve: • TACE: 63% • Bland: 50% • Control: 27% Llovet et al, Lancet 2002

  23. Guidelines Recommendation for TACE “The evidence for a survival benefit with TACE is sound and that this useful procedure should be used more often in the right clinical setting.” Saudi Guidelines for HCC, Ann Saudi Med 2006 “TACE is recommended as first line non-curative therapy for non-surgical patients with large/multifocal HCC who do not have vascular invasion or extrahepatic spread”. AASLD Practice Guidelines: HCC; Hepatology 2005

  24. Approach in Non-Cirrhotic Patient No Cirrhosis • Resection candidate • Normal bilirubin • No portal HTN • No extra-hepatic spread • Technically resectable Not Resection candidate • Multifocal (>3) • Lesion >4 cm • Less than 3 lesions • Smaller than 3 cm Resection TACE TACE Local ablation Saudi HCC Guidelines. Ann Saudi Med 2006

  25. Approach in Child-Pugh ‘A’ Cirrhotic Child-Pugh Class A Timely transplant available Yes No • ≤3 lesions each <3 cm • 1 lesion <5 cm • No extra hepatic spread • Resection candidate • Normal bilirubin • No portal HTN • No extra-hepatic spread • Technically resectable Not Resection candidate Transplant • Multifocal (>3) • Lesion >4 cm • Less than 3 lesions • Smaller than 3 cm Resection TACE TACE Local ablation Local ablative therapy or TACE may be used while awaiting liver transplant Saudi HCC Guidelines. Ann Saudi Med 2006

  26. Approach in Child-Pugh ‘B’ Cirrhotic Child-Pugh Class B Timely transplant available Yes No • Multifocal (>3) • Lesion >4 cm • ≤3 lesions each <3 cm • 1 lesion <5 cm • No extra hepatic spread • Less than 3 lesions • Smaller than 3 cm Transplant TACE TACE Local ablation therapy Saudi HCC Guidelines. Ann Saudi Med 2006

  27. Summary • HCC is essentially diagnosed by non-invasive criteria which is a combination of serology and imaging means. • Liver biopsy is to be performed only where considerable doubt exists for the diagnosis • Recent advances in ablative therapy (RFA) and improved survival with TACE are encouraging; that these should be used more frequently. • LT remains the curative treatment of choice.

  28. Saudi Gastroenterology AssociationGuidelinesDiagnosis & Management of HCCTechnical Review & Practice Recommendations www.saudiannals.net/SGAHCCguidelines/

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