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High-Intensity Focused Ultrasound for Hepatocellular Carcinoma
Joint Hospital Surgical Grand RoundQueen Mary Hospital
19/10/2013
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How HIFU worksIndications / ContraindicationsComplicationsCurrent results
BACKGROUND
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Hepatocellular carcinoma
• Most common primary liver cancer
• Only 15% resectable disease on presentation– Inadequate liver function– Multifocality
• Local ablative therapies for unresectable disease
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Local ablative therapy
• Radiofrequency ablation• Ethanol injection• Microwave ablation
• High-intensity focused ultrasound
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HOW HIFU WORKSIndications / ContraindicationsComplicationsCurrent results
Background
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High-Intensity Focused Ultrasound
• Focused ultrasound energy (0.8MHz) from distant transducer
• Hyperthermia• Coagulative necrosis
• Intact tissues in between
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• Animal studies in 1940s• Intended for treatment
of Parkinson disease
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Current clinical applications1990s: Transrectal HIFU for prostate cancer
2000s:MRI guided HIFU for uterine fibroid
Under investigation: Pancreatic tumour, bone tumours etc.
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Ultrasound guided HIFU system
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Ultrasound guided HIFU system
Water tank
Therapeutic ultrasound transducer
Diagnostic ultrasound probe
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Procedure
• General anaesthesia– Immobilization– Interval cessation of
ventilation
• Prone / right lateral position
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Procedure
• Planning with diagnostic ultrasound
• Slice-by-slice ablation from deep to superficial region
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Grayscale change
Before ablation After ablation
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Advantages / disadvantages
• Advantages– No internal bleeding– No needle tract seeding– Less liver derangement
• Disadvantages– Needs general anaesthesia– Lengthened procedure
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INDICATIONS / CONTRAINDICATIONSComplicationsCurrent results
BackgroundHow HIFU works
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Indications
• Small tumour– Less than 3cm: ablation rate >85%
• Centrally located / liver dome tumour• Adjacent to major bile duct / veins
• Child’s C liver function• Gross ascites
Cheung TT et al. HPB 2013
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Liver dome tumour
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Liver dome tumour
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Tumour adjacent to major vein
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Tumour adjacent to major vein
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Indications
• Small tumour– Less than 3cm: ablation rate >85%
• Centrally located / liver dome tumour• Adjacent to major bile duct / veins
• Child’s C liver function• Gross ascites
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Gross ascites
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Contraindications
• Not fit for general anaesthesia• Cannot assume treatment position
• Very poor liver function
• Lesion not visualized by USG• Overlying hollow viscus• Deep tumour• Tumour close to overlying rib
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Deep tumour
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Tumour close to rib
Pre-ablation Post-ablation
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COMPLICATIONSCurrent results
BackgroundHow HIFU worksIndications / Contraindications
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Complications (10-20%)Skin burn Bruising
• Pneumothorax• Incomplete ablation (10% for small tumours)
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CURRENT RESULTS
BackgroundHow HIFU worksIndications / ContraindicationsComplications
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• Unresectable HCC (n=49)– Child’s A (n=41) and B (n=8) cirrhosis– Median size 2.2cm (0.9-8cm)
Ng KK et al. Annals of Surgery 2011
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Unresectable HCC
• Ablation rate 79.5% (n=39)
• Risk factor: median tumour size (2.3cm vs. 3.8cm; p=0.03)
Ng KK et al. Annals of Surgery 2011
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SMALL HCCHIFU v.s. RFA
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• Small (<3cm) unresectable HCC (n=106)– Percutaneous RFA if feasible (n=59)– HIFU (n=47) if• Technically difficult percutaneous RFA
– Liver dome tumour– Ascites
• Child’s B cirrhosisCheung TT et al. HPB 2013
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HIFU vs. RFAHIFU (n=47) RFA (n=59) p
Child-Pugh class 0.001
A 31 (66%) 54 (91%)
B 16 (34%) 5 (9%)
Tumour size (cm) 1.5 (0.8-2.7) 1.9 (1.0-2.8) 0.006
Complete ablation 41 (87.2%) 56 (94.9%) 0.290
Complication rates 21% 9% 0.060
Skin burn (n=2) Pleural effusion (n=2)
Pneumothorax (n=2) Liver abscess (n=1)
Chest wall oedema (n=1)
Major complications 6.4% 6.8% >0.05
Hospital stay (day) 4 6 0.028
Cheung TT et al. HPB 2013
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Survival
34%
26%
81%80%
Cheung TT et al. HPB 2013
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TUMOURS CLOSE TO PEDICLES
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• Liver tumours (n=30) and pancreatic tumours (n=6)• Tumour <1cm from – IVC / hepatic /portal veins (n=27)– Bile ducts (n=4)
• 1 portal vein thrombosis (Pancreatic cancer)• No bile duct injury
Franco O et al. AJR 2013; 195
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• HCC (n=39) with close proximity to major veins
• No venous thrombosis / bile duct injury
Zhang L et al. Eur Radiol 2008
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LOCALLY ADVANCED HCCSpecial condition
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• Locally advanced (4-14cm, mean 10.5cm) HCC (n=50)– Randomized controlled trial– TACE + HIFU (n=24)– TACE only (n=26)
Wu F et al. Radiology 2005
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TACE + HIFU vs. TACE
TACE + HIFU(n=24) TACE (n=26) p
Child-Pugh class >0.05
A 24 (100%) 24 (92%)
B 0 (0%) 2 (8%)
Tumour size (cm) 10.03 11.26 >0.05
Course of treatment 1.2 1.5
Median reduction in tumour size at 6 month
52.9% 10.0% <0.01
Median survival (month) 11.3 4.0 0.004
Wu F et al. Radiology 2005
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Survival
TACE onlyTACE + HIFU
Wu F et al. Radiology 2005
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Locally advanced HCC
• Combined HIFU / TACE is a promising approach
• On-going trial in QMH
Wu F et al. Radiology 2005
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BRIDGING TO TRANSPLANTSpecial condition
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• Retrospective study
• Transplant candidates for HCC (n=49)– Bridging HIFU (n=5)– Bridging TACE (n=29)– No bridging therapy (n=15)
• Non-transplant candidates with HIFU (n=5)
Cheung TT et al. WJG 2013
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Bridging to transplant
HIFU(n=10) TACE (n=29) p
Child-Pugh class 0.267
A 3 (30%) 17 (58.6%)
B 6 (60%) 12 (41.4%)
C 1 (10%) 0 (0%)
Tumour size (cm) 2.6 (1.2-4.0) 2.0(0.8-4.3) 0.960
Number of tumour 1 (1-2) 1 (1-3) 0.172
Complete response 9 (90%) 1 (3%) 0.00
Partial response 1 (10%) 14 (48%) 0.00
Progressive disease 0 14 (48%) 0.00
Cheung TT et al. WJG 2013
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Bridging to transplant
• 3 patients in HIFU group received liver transplant
• Pathology– Complete necrosis (n=2)– 90% necrosis (n=1)
Cheung TT et al. WJG 2013
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Liver transplant candidate
• Effective bridging therapy to liver transplant
Cheung TT et al. WJG 2013
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Summary
• Current applications– Ablative therapy for small unresectable HCC• Child’s C liver function • Tumour close to major pedicle
– Combined with TACE for large HCC– Bridging therapy to liver transplantation
• Under investigation• More clinical studies warranted