hepatocellular carcinoma diagnostic and therapeutic strategies faisal sanai consultant hepatologist...

Hepatocellular CarcinomaDiagnostic and Therapeutic

Strategies

Hepatocellular CarcinomaDiagnostic and Therapeutic

Strategies

Faisal Sanai

Consultant HepatologistRiyadh Military Hospital

Faisal Sanai

Consultant HepatologistRiyadh Military Hospital

10th International Advanced Medicine Symposium

22

Tumor Markers for HCCTumor Markers for HCC

-l-Fucosidase.

5’- nucleotide phosphodiesterase.

Des3 carboxy prothrombin. CA 19-9, CA 125, ALP.

Alpha Fetoprotein. Fucosylated AFP.

-l-Fucosidase.

5’- nucleotide phosphodiesterase.

Des3 carboxy prothrombin. CA 19-9, CA 125, ALP.

Alpha Fetoprotein. Fucosylated AFP.

33

Alpha FetoproteinSensitivity and Specificity Issues

Alpha FetoproteinSensitivity and Specificity Issues

GI tumors: 10 – 20%.

Cirrhosis: 40%.

Acute and chronic hepatitis: 20%.

Pregnancy.

Gonadal tumors: 80%.

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.

Ethnicity.

Etiology of liver disease.

Treatment of underlying liver disease.

Tumor staging.

Sensitivity patterns for HCC vary widely: 32 Sensitivity patterns for HCC vary widely: 32 – 93%– 93%

Colli A, et al. Am J Gastro 2006.

Sensitivity patterns for HCC vary widely: 32 Sensitivity patterns for HCC vary widely: 32 – 93%– 93%

Colli A, et al. Am J Gastro 2006.

44

Alpha FetoproteinChange in HCC Detection by Changing Cut-

off Points

Alpha FetoproteinChange in HCC Detection by Changing Cut-

off Points

Diagnostic Diagnostic CriteriaCriteria Sensitivity (%)Sensitivity (%) Specificity (%)Specificity (%)

>615 ng/ml>615 ng/ml 56.456.4 96.496.4

>445 ng/ml>445 ng/ml 56.456.4 94.594.5

>100 ng/ml>100 ng/ml 72.672.6 70.970.9

>20 ng/ml>20 ng/ml 87.187.1 30.930.9

Poon TCW, Clin Liv Dis 2001Poon TCW, Clin Liv Dis 2001

55

Diagnostic Yield of U/SDiagnostic 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

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

66

CT Scan for HCC DiagnosisCT 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

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

77

The CT Modality of ChoiceThe 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

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%

88

AngiographyDoes the Route Make Any Difference ?

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

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

99

To Biopsy or Not to Biopsy…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 1999Horigome H, et al J Gastro & Hepatol 1999

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 1999Horigome H, et al J Gastro & Hepatol 1999““Only where considerable doubt exists, will Only where considerable doubt exists, will

a biopsy of the lesion be required.”a biopsy of the lesion be required.”BSG Guidelines – Ryder SD, Gut 2003.

““Only where considerable doubt exists, will Only where considerable doubt exists, will a biopsy of the lesion be required.”a biopsy of the lesion be required.”

BSG Guidelines – Ryder SD, Gut 2003.

1010

Needle Track SeedingNeedle 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

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

1111

BiopsyThe Guidelines

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 2001Abdo A, et al. Saudi Guidelines for HCC, Ann Saudi Med 2006


Lesions <1 cm should not be biopsied.

Lesions 1 - 2 cm should have FNA + biopsy.

Conclusions of EASL 2000, J Hepatol 2001


Lesions >2 cm should not be biopsied in presence of diagnostic clinical criteria.

Conclusions of EASL 2000, J Hepatol 2001Abdo A, et al. Saudi Guidelines for HCC, Ann Saudi Med 2006


1212

Setting Diagnostic Criteria 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 2006Conclusions of EASL 2000, J Hepatol 2001

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 2006Conclusions of EASL 2000, J Hepatol 2001

1313

Surveillance and Recall Strategy for HCC

Surveillance and Recall Strategy for HCC

Cirrhotic patients (US + AFP/6 m)Cirrhotic patients (US + AFP/6 m)Cirrhotic patients (US + AFP/6 m)Cirrhotic patients (US + AFP/6 m)

HCC**HCC**HCC**HCC** Surveillance US + AFP/6 mSurveillance US + AFP/6 mSurveillance US + AFP/6 mSurveillance US + AFP/6 m

Liver noduleLiver noduleLiver noduleLiver nodule No noduleNo noduleNo noduleNo nodule

1 cm1 cm <1 cm<1 cm Increased AFP*Increased AFP* Normal AFPNormal AFP

<2 cm<2 cm >2 cm>2 cm US/3mUS/3m Spiral CTSpiral CT

FNABFNAB AFP 400 ng/mLCT/MRI/Angiography

AFP 400 ng/mLCT/MRI/Angiography

No HCCNo HCC

*AFP levels to be defined; **Pathological confirmation or non-invasive criteria*AFP levels to be defined; **Pathological confirmation or non-invasive criteria

1414

Decision making in HCC Treatment

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.

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.

1515

Liver Transplantation for HCCLiver 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).

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 2001Saudi Guidelines for HCC, Ann Saudi Med 2006Bruix J, et al. AASLD Guidelines 2005

1616

Milan Milan CriteriaCriteria 94%94% 88%88%

UCSF UCSF CriteriaCriteria 90%90% 90%90%

Liver Transplantation for HCC

Expanding the Milan Criteria

Survival

Yao et al. Hepatology 2005, 197A

UCSF Criteria: (single lesion < 6.5 cm; ≤ 3 in number, < 4.5 cm; combined diameter < 8cm)

1717

The Optimal Resection Candidate

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.

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.

1818

ResectionsOutcome

ResectionsOutcome

Recurrence: 5 years >70%.

Survival: 3 years: 38 - 65%. 5 years: 33 - 44%.

Decompensation: 50%.

Recurrence: 5 years >70%.

Survival: 3 years: 38 - 65%. 5 years: 33 - 44%.

Decompensation: 50%.

Song TJ, et al. Gastroenterology 2004

1919

Local Ablative Therapies for HCC

PEI: Livraghi T, et al., J Hepatol 1995


PEI: Livraghi T, et al., J Hepatol 1995

Child - AChild - A

ResectionResection

79% (p 79% (p <0.001)<0.001)

P E IP E I

71% (p 71% (p <0.001)<0.001)

No TreatmentNo Treatment

26%26%

Child - BChild - B

ResectionResection

40% (p 40% (p <0.01)<0.01)

P E IP E I

41% (p 41% (p <0.001)<0.001)

No TreatmentNo Treatment

13%13%

Survival: 3 years, 391 patients, 1 lesion, <5 cmSurvival: 3 years, 391 patients, 1 lesion, <5 cm

2020



Radiofrequency Ablation (Lencioni R et al, Radiology 2003)

Randomized trial: RFA vs PEI. Child A or B in accordance with Milan criteria.

Radiofrequency Ablation (Lencioni R et al, Radiology 2003)

Randomized trial: RFA vs PEI. Child A or B in accordance with Milan criteria.

SurvivalSurvival 1 year1 year 2 years2 years

RFARFA 100%100% 98%98%pp = 0.138 = 0.138

PEIPEI 96%96% 88%88%

SurvivalSurvival1 Year1 Year

89%89%

3 years3 years

62%62%

5 years5 years

33%33%

Buscarini L et al., Eur Radiol 2001Buscarini L et al., Eur Radiol 2001

2121

Rationale for Embolization Therapy

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

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

2222

Improved Survival with TACEImproved 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

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

2323

Guidelines Recommendation for TACE

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

“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

2424

Approach in Non-Cirrhotic Patient

Approach in Non-Cirrhotic Patient

Saudi HCC Guidelines. Ann Saudi Med 2006Saudi HCC Guidelines. Ann Saudi Med 2006

No CirrhosisNo CirrhosisNo CirrhosisNo Cirrhosis

Resection candidateResection candidate Normal bilirubinNormal bilirubin No portal HTNNo portal HTN No extra-hepatic spreadNo extra-hepatic spread Technically resectableTechnically resectable


Not Resection candidateNot Resection candidateNot Resection candidateNot Resection candidate

ResectionResectionResectionResection

Multifocal (>3)Multifocal (>3) Lesion >4 cmLesion >4 cm


Less than 3 lesionsLess than 3 lesions Smaller than 3 cmSmaller than 3 cm


TACETACETACETACE TACETACETACETACE Local ablationLocal ablationLocal ablationLocal ablation

2525

Approach in Child-Pugh ‘A’ Cirrhotic

Approach in Child-Pugh ‘A’ Cirrhotic

Child-Pugh Class AChild-Pugh Class AChild-Pugh Class AChild-Pugh Class A

Timely transplant availableTimely transplant availableTimely transplant availableTimely transplant available

YesYes NoNo

≤ ≤3 lesions each <3 cm3 lesions each <3 cm 1 lesion <5 cm1 lesion <5 cm No extra hepatic spreadNo extra hepatic spread




Not ResectionNot Resectioncandidatecandidate

Not ResectionNot Resectioncandidatecandidate

TransplantTransplantTransplantTransplant

ResectionResectionResectionResection

TACETACETACETACE TACETACETACETACE Local ablationLocal ablationLocal ablationLocal ablation






Local ablative therapy or TACE may be used while awaiting liver transplantLocal ablative therapy or TACE may be used while awaiting liver transplant

2626

Approach in Child-Pugh ‘B’ Cirrhotic

Approach in Child-Pugh ‘B’ Cirrhotic

Child-Pugh Class BChild-Pugh Class BChild-Pugh Class BChild-Pugh Class B

Timely transplant availableTimely transplant availableTimely transplant availableTimely transplant available

YesYes NoNo

TransplantTransplantTransplantTransplant TACETACETACETACE TACETACETACETACE Local ablationLocal ablationtherapytherapy

Local ablationLocal ablationtherapytherapy








2828

SummarySummary

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.

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.

2929

www.saudiannals.net/SGAHCCguidelines/

Saudi Gastroenterology Association Guidelines

Diagnosis & Management of HCCTechnical Review & Practice Recommendations

Saudi Gastroenterology Association Guidelines

Diagnosis & Management of HCCTechnical Review & Practice Recommendations

hepatocellular carcinoma diagnostic and therapeutic strategies faisal sanai consultant hepatologist...

Documents

sensitivity of ct

reduced sensitivity

sensitivity patterns

alpha fetoprotein sensitivity

j gastro

arterial phase ct

w ct angiography

w ct portography