Hepatocellular Carcinoma Diagnostic and Therapeutic Strategies

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Hepatocellular CarcinomaDiagnostic and
Therapeutic Strategies

• Faisal Sanai
• Consultant Hepatologist
• Riyadh Military Hospital

10th International Advanced Medicine Symposium
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Tumor Markers for HCC

• ?-l-Fucosidase.
• 5- nucleotide phosphodiesterase.
• Des3 ? carboxy prothrombin.
• CA 19-9, CA 125, ALP.
• Alpha Fetoprotein.
• Fucosylated AFP.

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Alpha FetoproteinSensitivity and Specificity
Issues

• 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.

Sensitivity patterns for HCC vary widely 32
93 Colli A, et al. Am J Gastro 2006.
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Alpha FetoproteinChange in HCC Detection by
Changing Cut-off Points
Diagnostic Criteria Sensitivity () Specificity ()
gt615 ng/ml 56.4 96.4
gt445 ng/ml 56.4 94.5
gt100 ng/ml 72.6 70.9
gt20 ng/ml 87.1 30.9
Poon TCW, Clin Liv Dis 2001
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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

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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

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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

Earlier Report Recent Report
Sensitivity 93 97 78
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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

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To Biopsy or Not to Biopsy

• Pre-existing cirrhosis mass gt2 cm
• gt95 chance of HCC.
• Pre-existing cirrhosis mass lt2 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.
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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 lt3cm and low AFP
• Levy I, et al. Ann Surg 2001

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BiopsyThe Guidelines

• Lesions lt1 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 gt2 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

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Setting Diagnostic Criteria

• Histological diagnosis.
• Presence of classic appearance in one imaging
  modality AFP gt400 µg/L appropriate clinical
  setting.
• Presence of normal AFP classic (gt2 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

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Surveillance and Recall Strategy for HCC
Cirrhotic patients (US AFP/6 m)
Liver nodule
No nodule
?1 cm
lt1 cm
Increased AFP
Normal AFP
lt2 cm
gt2 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
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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.

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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 lt 5 cm 3 in number, lt 3 cm).

Conclusions of EASL 2000, J Hepatol 2001 Saudi
Guidelines for HCC, Ann Saudi Med 2006 Bruix J,
et al. AASLD Guidelines 2005
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Liver Transplantation for HCCExpanding the Milan
Criteria
UCSF Criteria (single lesion lt 6.5 cm 3 in
number, lt 4.5 cm combined diameter lt 8cm)
Survival
Milan Criteria 94 88
UCSF Criteria 90 90
Yao et al. Hepatology 2005, 197A
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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 gt10 mmHg
• Oesophageal varices
• Splenomegaly ? plats lt105
• Patient is not a candidate for LT treatment.
• Solitary lesions lt5 cm.

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ResectionsOutcome

• Recurrence
• 5 years gt70.
• Survival
• 3 years 38 - 65.
• 5 years 33 - 44.
• Decompensation
• 50.

Song TJ, et al. Gastroenterology 2004
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Local Ablative Therapies for HCCPEI Livraghi T,
et al., J Hepatol 1995
Survival 3 years, 391 patients, 1 lesion, lt5 cm
Child - A Resection 79 (p lt0.001) P E I 71 (p lt0.001) No Treatment 26
Child - B Resection 40 (p lt0.01) P E I 41 (p lt0.001) No Treatment 13
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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.

Survival 1 year 2 years
RFA 100 98 p 0.138
PEI 96 88 p 0.138
Survival 1 Year 89 3 years 62 5 years 33
Buscarini L et al., Eur Radiol 2001
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Rationale for Embolization Therapy

• HCC blood supply gt90 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

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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

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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

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Approach in Non-Cirrhotic Patient
No Cirrhosis

• Resection candidate
• Normal bilirubin
• No portal HTN
• No extra-hepatic spread
• Technically resectable

Not Resection candidate

• Multifocal (gt3)
• Lesion gt4 cm

• Less than 3 lesions
• Smaller than 3 cm

Resection
TACE
TACE
Local ablation
Saudi HCC Guidelines. Ann Saudi Med 2006
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Approach in Child-Pugh A Cirrhotic
Child-Pugh Class A
Timely transplant available
Yes
No

• 3 lesions each lt3 cm
• 1 lesion lt5 cm
• No extra hepatic spread

• Resection candidate
• Normal bilirubin
• No portal HTN
• No extra-hepatic spread
• Technically resectable

Not Resection candidate
Transplant

• Multifocal (gt3)
• Lesion gt4 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 (gt3)
• Lesion gt4 cm

• 3 lesions each lt3 cm
• 1 lesion lt5 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
Approach in Child-Pugh C Cirrhotic
Child-Pugh Class C
Timely transplant available

• 3 lesions each lt3 cm
• 1 lesion lt5 cm
• No extra hepatic spread

• Good performance
• status
• lt50 years old

• Poor performance
• status
• gt50 years old

Transplant

• Cirrhosis complication
• management
• Consider enrollment in
• systemic chemotherapy
• trials

• Cirrhosis complication
• management
• Palliative symptomatic
• treatment

Saudi HCC Guidelines. Ann Saudi Med 2006
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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.

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Saudi Gastroenterology Association
GuidelinesDiagnosis Management of
HCCTechnical Review Practice Recommendations
www.saudiannals.net/SGAHCCguidelines/