3. Minimally invasive treatments for HCC
Description of techniques
Review of the evidence
What is best?
IR as adjunctive treatment
Bridging and downstaging to OLT
Portal vein embolization
Case examples: successes and failures
My practice – the first 2.5 years, by the
numbers
4. “Resection with wide “OLT is the best available
margins is the treatment of curative treatment for HCC
choice for HCC in patients
in cirrhotic livers”
without cirrhosis”
Jarnagin W, et al. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB 2010;12:302-310.
7. Ethanol injection causes vessel
thrombosis and protein denaturation
• Complete necrosis of small (<2 cm) HCC
can be achieved
• Tumors near sensitive organs can be
treated; no heat sink effect
5-year survival of 32-38%
Disadvantages
• Multiple treatment sessions needed
• Uncertain ablation zone
• High local recurrence rate (17-38%)
8. RF current induces thermal coagulation
necrosis around an electrode
• Complete ablation rates >80% for small to
medium HCC
• Local recurrence uncommon (1-12%)
5-year survival of 40-58%
Disadvantages
• Relies on thermal conduction (limited
ablation size)
Best for tumors <3 cm
Increasing technical failure and local recurrence for
tumors >3 cm
• Heat sink effect
• Slow
McWilliams J, et al. Percutaneous ablation of hepatocellular carcinoma: current status. J Vasc Interv Radiol 2010;21:S204-S213.
Hinshaw J. The role of image-guided tumor ablation in the management of liver cancer. Cancer News review article.
9. Three RCTs and two meta-analyses
confirm superiority of RFA over PEI
for small HCC
• 5-year survival about 15% better for RFA
versus PEI
PEI: 5-year RFA: 5-year
survival 35% survival 50%
• Less local tumor recurrence for RFA
• 3x fewer treatment sessions for RFA
PEI still useful for tumors in
sensitive locations
Shiina S, Teratani T, Obi S, et al. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma.
Gastroenterology 2005; 129:122–130.
Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular
carcinoma or 4 cm. Gastroenterology 2004; 127:1714–1723.
Lencioni RA, Allgaler HP, Cloni D, et al. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation
versus percutaneous ethanol injection. Radiology 2003; 228:235–240.
10. Next-generation RF ablation electrodes
are available
• Internal cooling
• Saline injection
• Expandable tines
Ablation zones of 4-7 cm are
achievable
McWilliams J, et al. Percutaneous ablation of hepatocellular carcinoma: current status. J Vasc Interv Radiol 2010;21:S204-S213.
11. Microwave creates a field of electromagnetic energy
and thermal coagulation around an antenna
• Active heating not reliant on conduction (faster, larger ablation
zones)
• Less heat-sink effect
• Multiple antennae can be activated simultaneously
5-year survival of ????
Next-generation 2450 MHz MW ablation devices now
available
• 17-gauge antennae
• CO2 based internal cooling
• High power (140 watts)
• Large ablation zones (3.5 x 5 cm)
McWilliams J, et al. Percutaneous ablation of hepatocellular carcinoma: current status. J Vasc Interv Radiol 2010;21:S204-S213.
12. “Local ablation is safe and effective therapy for patients
who cannot undergo resection, or as a bridge to
transplantation.”
American Association for Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL).
14. HCC takes its blood supply almost
exclusively from the hepatic artery
Surrounding normal liver has dual
blood supply (with portal vein)
Chemotherapy + embolic agent
administered into hepatic artery
should selectively kill tumor while
sparing normal liver
15. 1. Select tumor-bearing artery
2. Embolize to near-stasis or stasis
• Chemotherapy
(doxorubicin, cisplatin, mitomycin C)
• Lipiodol vehicle; selectively retained by HCC
Causes ischemia
Extends contact of chemotherapy with tumor
• Finish embolization with gelfoam or particles
16. 6 randomized trials in 1990s
showed no benefit of TACE for
unresectable HCC
• Selection criteria not stringent
Severe underlying liver disease
• Many patients not aggressively re-treated
Objective responses to TACE are not maintained with
time
• Nonselective embolization often used
17. RCT of TACE vs. symptomatic treatment for unresectable HCC
Llovet: 112 patients
• Mostly Hepatitis C
• 75% had multinodular tumor
• Mean diameter of main nodule was ~5 cm
• About 75% Child A, 25% Child B
• Repeated Doxorubicin/Ethiodol TACE (mean 3 treatments/patient)
Lo: 80 patients
• Mostly Hepatitis B
• 60% had multifocal tumor
• Mean diameter of main nodule was ~7 cm
• ~25% had right or left PV obstruction
• Repeated Cisplatin/Ethiodol TACE (mean 4.5 treatments/patient)
18. RCT of TACE vs. symptomatic treatment for unresectable HCC
Llovet: 112 patients
3-year survival:
29% with TACE
17% with supportive care
Lo: 80 patients
3-year survival:
26% with TACE
3% with supportive care
19. Meta analysis of cTACE
• TACE reduced 2-year mortality (OR 0.54) compared to symptomatic
treatment
Camma C, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 2002.
20. Cohort study of 8510 patients having cTACE
• Initial treatment
• Unresectable HCC
• No extrahepatic disease
• 5-year survival 26%
Takayasu K, et al. Prospective Cohort Study of Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma in 8510 Patients. Gastroenterology 2006.
21. AFP Child class Max tumor size
• <20 = 34% • A = 33% • <=2 cm = 39%
• 21-200 = 27% • B = 21% • 2.1-3 cm = 28%
• 201-1000 = 19% • C = 8% • 3.1 – 5 cm = 23%
• >1000 = 15% • >5 cm = 16%
# of lesions PV invasion
• 1 = 33% • None = 28%
• 2-3 = 24% • Peripheral branch = 12%
• 4 or more = 16% • Left or right = 11%
• Main = 0%
Takayasu K, et al. Prospective Cohort Study of Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma in 8510 Patients. Gastroenterology 2006.
22. “TACE is first-line non-curative therapy for
non-surgical patients with large or multifocal
HCC who do not have vascular invasion or
extrahepatic spread (level I evidence).”
American Association for Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL).
23. Chemotherapy in lipiodol washes out
of tumor quickly
• Less effective tumor kill
• More systemic side effects
Chemotherapy loaded onto a particle
can be eluted slowly
• LC beads: Size-calibrated spherical hydrogel
particle which can be loaded with doxorubicin
• Chemotherapeutic elutes gradually over
weeks, though tumor necrosis greatest at 7-
14 days
24. RCT vs. bland embo
Mid-term survival data
• 41 DEB-TACE vs. 43 bland embo • 71 patients
• Child A and B, ECOG 0 or 1 • Child A and B, ECOG 0 or 1
• Procedures q2 months up to 3; 100-300 and • Exclusion criteria: Creatinine >2, Portosystemic
300-500 micron LC beads shunt, Hepatofugal blood flow, Main portal vein
thrombus, extrahepatic disease
DEB-TACE: • 1-4 procedures, q3 months as needed. 100-
• Higher complete response rate at 6 months 300 and 300-500 micron LC beads with 150
(27 vs 18%) mg doxorubicin per treatment.
• Lower recurrence rate at 12 months (46% vs
78%) 88% survival at 30 months (better
• Longer time to progression (42 vs 36 weeks) than historical cTACE)
25. 212 patients randomized to DEB-TACE with LC beads
vs. cTACE with doxorubicin
• Child A and B, ECOG 0 or 1
• Exclusion criteria: Bili >3, Vascular invasion, >50% tumor, extrahepatic
spread, AST or ALT >5x normal
• 1 vial 300-500, 1 vial 500-700 micron LC beads, 75 mg doxo/vial
vs. 150 mg doxo in Ethiodol with operator choice embolic
• Treatments q2 months up to 3 treatments; tumor response
evaluated at 6 months
Tendency toward better response with DEB-TACE (52
vs. 44%)
Significant reduction in liver toxicity and side effects with
DEB-TACE
Survival was not an endpoint (too short f/u)
26. Expandable microspheres made of
sodium acrylate/vinyl alcohol
copolymer
Ionically binds doxorubicin
Arrive dehydrated; when placed in
saline or contrast, they increase in
volume (50-100 micron goes to
150-300 micron)
Soft and deformable, conform to
vessel wall
27. Single-arm trial of 50 patients
• Child A
• Exclusion criteria
Tumor size >10 cm, Portal vein invasion, Extrahepatic
disease
• 50 mg doxo or epirubicin per
treatment, repeated “on demand” ? Survival ?
• 6-month results: ? Durable effect ?
CR in 52%
PR in 26%
PD in 23% ? Comparison to LC
Only 31/50 followed up beads or cTACE ?
“Safe, well-tolerated and efficient
agent to produce tumor necrosis”
28. 281 consecutive patients with PV 164 patients with segmental or 125 patients with main PV
invasion studied retrospectively major PV invasion invasion
• 84 treated with TACE vs. 80 with • 83 treated with superselective
supportive care TACE vs. 42 with supportive care
Aggressive repeated TACE was
• 1-year survival 31% vs. 4% • Repeated TACE showed survival
well tolerated and showed
• 2-year survival 9% vs. 0% benefit (5.6 vs. 2.2 months)
significant survival benefits
• Significant advantage for TACE in • 29% morbidity rate (similar to
(median survival 10 vs 2 months) both segmental and major PV supportive care), no mortality
invasion
• No procedure-related mortality
29. Retrospective study of >1000
patients
• 843 patients <70 compared to 197
patients >70
• Elderly patients had more comorbid
disease (64 vs 33%) but had earlier
stage of HCC
• Overall survival better for the elderly
14 vs. 8 months
TACE tolerated equally well
TACE is good for young and old
alike
31. Transarterial administration of radioactive
microspheres (Yttrium-90)
• Half-life 64 hours; decays into stable zirconium-90
• Beta-emitter with path length of 2.5 mm
• Particles lodge in the tumor, producing very high local
radiation dose (100-1000 Gy or more)
• Not dependent on flow occlusion
TheraSpheres
• FDA approved under Humanitarian Device Exemption
for use in treatment of HCC
• Glass particle, 15-35 micron diameter
• 1.2-8 million spheres per vial (3GBq)
• Minimally embolic
Two scenarios must be avoided with Y90
• Shunting into lung (radiation pneumonitis)
• Nontarget embolization of GI tract (ulceration)
32. Liver-only or liver-dominant tumor, not suitable
for radical therapy
• Resection
• Liver transplantation
• Ablation
Preserved functional status
• ECOG 0-2
Preserved hepatic function
• Total bili <= 2.0
• Albumin >= 3.0
• No ascites or other clinical signs of liver failure
Low risk of pulmonary effects
• <20% hepatopulmonary shunt
• <30 Gy expected dose delivery to lungs (<50 Gy for
multiple infusions)
33. 1. Superior mesenteric angiogram
• Detect hepatic arterial variations
• Determine patency of portal vein and hepatopetal flow
2. Complete celiac angiography
• Map arterial anatomy
• Detect extrahepatic supply to tumor
• Det
3. Prophylactic embolization of any vessel in the
treatment zone which does not lead to liver
• GDA
• Right gastric
• Accessory left gastric
• Falciform
• Supraduodenal
• Cystic
4. Place microcatheter at site of expected Y90 treatment
and administer 4 mCi Tc-99m MAA
• Similar size particles to TheraSpheres
• Perform MAA scan to see distribution of particles
• Measure lung-shunt fraction (must be <20%)
• Detect any mesenteric flow
34. 1. 2 weeks after mesenteric
mapping, patient returns for Y90
administration
2. Repeat celiac/hepatic angiography
• Ensure continued occlusion of embolized
vessels
3. Position microcatheter in lobar artery
supplying the most tumor and infuse Y90
4. If bilobar disease, patient will return in 1
month for Y90 treatment of opposite lobe
35.
36. 108 patients with unresectable 291 patients with unresectable intermediate
intermediate or advanced HCC or advanced HCC
• No extrahepatic disease • PVT and limited extrahepatic disease allowed
• 17% BCLC A; 28% B; 52% C; 3% D
159 sessions of TheraSphere Y-90
• 40% response rate (almost all partial) 526 sessions of TheraSphere Y-90
• Time to progression 10 months • 42% response rate
• Overall median survival 16 months • Time to progression 8 months
• Transient fatigue syndrome and • Survival: 17 months Child A; 8 months Child B
abldominal pain • Fatigue, pain, nausea, elevated LFTs (all 20-50%)
37. 8-center study of 325 patients with
unresectable intermediate or advanced
HCC
• 82% Child A, 18% Child B
• 24% solitary, 76% multifocal
• 9% extrahepatic metastases
• 14% branch PV occlusion, 10% main
Overall median survival 12.8 months
Predictors of poor survival:
• ECOG status
• >5 nodules
• INR >1.2
• Extrahepatic disease
38. Y90 expected to be better tolerated than TACE
in patients with PV invasion
• Y-90 is less embolic; therefore less risk of hepatic
infarction
• Median overall survival 7-10 months
4 months in main PV invasion
• Mostly grade 1 and 2 toxicities
Abdominal pain (38%)
Nausea (28%)
Fatigue (22%)
Ascites (13%)
Encephalopathy (13%)
Y90 is safe and shows tumor response in
patients with branch or lobar PV invasion.
40. 185 patients with resectable early- 419 patients with resectable HCC
stage HCC and Child A cirrhosis • 46 had TACE
• 73 had superselective TACE • 311 had resection
• 112 had resection • 62 refused treatment (supportive
care)
5-year survival
5-year survival
• TACE: 52% (ns)
• TACE: 34% (ns)
• Resection: 57% (ns)
• Resection: 43% (ns)
• Supportive care: 7% (p = 0.0001)
41. 3225 patients with HCC 87 patients with resectable HCC
retrospectively grouped by clinical • 20 had TACE
prognosis and tumor burden • 67 had resection
Compensated patients with 3 or fewer 5-year survival
tumors, any size • TACE: 18%
• Surgery: 45-55% 5-year survival • Resection: 55% (p<0.05)
• TACE: 17-20% 5-year survival
42. 115 RFA vs. 115 surgery 180 patients with solitary HCC <5 cm
• HCC within Milan criteria • Half had HCC <3 cm, half had HCC 3-5 cm
Survival at 5 years: Survival at 4 years:
• RFA 55% • RFA 68%
• Surgery 76% (p<0.05) • Surgery 64%
DFS at 4 years:
DFS at 5 years:
• RFA 46%
• RFA 29%
• Surgery 52%
• Surgery 51% (p<0.05)
RFA had fewer adverse events (55% vs 4%)
RFA had fewer adverse events (32 vs. 5)
43. 5317 American patients with HCC
7185 patients with HCC (3 tumors up to 3 • Median tumor size 6 cm
cm) and Child A/B liver function • 52% solitary; 28% multiple; 20% extrahepatic
• 30-day mortality was 8% resection; 3% OLT; 3%
3022 RFA patients ablation; 31% no or incomplete local therapy
• 55% tumor recurrence in 2 years • 5-year survival 67% OLT; 35% resection; 20% ablation;
• 1.6% death rate at median 10 months 3% no or incomplete local therapy
2857 resection patients Prognostic factors
• 35% tumor recurrence in 2 years • Disease extent
• 1.9% death rate at median 10 months • Tumor grade
• Tumor size
Relative risk or recurrence was 0.62 in • Vascular invasion
resection group; no difference in survival • Age
Selection bias is likely
44. 91 patients with unresectable HCC (up to 3 nodules, each up to
5 cm)
258 patients with hypervascular HCC (1 nodule
40 TACE patients
<5 cm or up to 3 nodules <3 cm)
• Mean 6 sessions
• 58% survival at 2 years • Mean tumor size 1.7 cm in both groups
• TACE group had more multifocal tumors, more
51 RFA patients peripheral tumors, more previously treated tumors
• Mean 1 session
• 72% survival at 2 years (ns)
133 TACE patients
Morbidity higher for RFA (28% vs. 10%) • Local recurrence 51% at 2 years
No treatment-related mortality
105 RFA patients
Similar time to progression • Local recurrence 40% at 2 years (p<0.05)
45. 790 patients with unresectable
intermediate-stage HCC +/- PVT
245 comparable patients with
unresectable intermediate-stage
99 had TheraSphere Y-90 vs. 691 had
HCC and no PVT
repetitive cTACE
• Overall median survival 11.5 vs. 8.5 months
123 underwent TheraSphere Y-90 (p<0.05)
vs. 122 had TACE • But, TACE group had more severe liver disease
• 72% vs. 69% response rate (ns) • No difference in survival after controlling for
• Time to progression 13 vs. 8 months underlying disease
(p=.046) • Y-90 (outpatient, 1 or 2 treatments) is compelling
• Overall median survival 20 vs. 17 months as a palliative treatment option compared to
(ns) TACE (inpatient stay, multiple treatments)
• Less abdominal pain and LFT increase
with Y90
46. 73 comparable patients with unresectable
HCC, ~35% with vascular invasion
• Segmental PV occlusion could have TACE or Y90
• Extensive PV occlusion favored Y90
38 underwent TheraSphere Y-90 vs. 35 had
TACE
• 7 Y90 patients and 2 TACE patients crossed over
• Median survival 8.0 vs. 10.3 months (ns)
• Mean total hospitalization (initial + re-hospitalization)
days 0.5 vs. 3.5 (p<0.001)
• Complication rate higher for TACE, mostly due to
more severe PES
48. 37 patients with solitary HCC 3.1-5.0
cm
89 patients with 93 HCC <3 cm
• TACE-RFA same day vs. RFA alone
• TACE then RFA 1 week later vs. RFA
• Slightly larger ablation size with TACE-RFA
alone
(5.0 vs. 4.1 cm)
• Local tumor progression 18% vs. 14% at 4
• Local tumor progression 6% vs. 39% at 3
years (ns)
years (p=.012)
• Overall survival 73% vs. 74% at 4 years
• Overall survival 93% vs. 80% (ns) (ns)
• Rate of major complications ~1% for both
• Rate of major complications ~2% in both
groups
groups
50. Interventional radiology plays a key role (maybe the
key role!) in liver cancer treatment
• Percutaneous ablation
• Early HCC
• TACE •
•
Preserved liver function: Resection or ablation
Compromised liver function: Transplantation
• Bridge to transplant with ablation or TACE
• Y-90
• Intermediate HCC:
• Preserved liver function: TACE, Y90 and/or ablation
• Portal vein embolization • Downstage to transplant if possible
• Compromised liver function: Supportive care
• Consider extended criteria OLT or LDLT
• Downstaging to transplant
• Advanced HCC:
• Bridging to transplant •
•
Preserved liver function: Sorafenib or Y90
Compromised liver function: Supportive care
• Percutaneous biopsy
• Transjugular pressure measurements
• Salvaging operative mishaps
51.
52. TS
65 y/o female
Hepatitis B cirrhosis
Routine screening US and CT demonstrated
two adjacent 4-cm HCCs
Not a surgical candidate TACE 1/26/2010: 75 mg
doxorubicin on LC beads
Outside Milan criteria for OLT
Referred for locoregional therapy and possible
down-staging
53. MRI 2/25/2010: No residual tumor.
Patient downstaged, exception points
awarded for OLT
TACE #2 6/8/2010
22.5 mg doxorubicin on
LC beads to R hepatic
Awaiting OLT artery
CT 4/24/2010:
Intrahepatic recurrence
54. TACE #3 11/18/2010
75 mg doxorubicin on
LC beads to R phrenic
and R hepatic arteries
MRI 10/25/2010:
Intrahepatic recurrence
55. MRI 12/20/2010: Minimal residual tumor
Successful OLT 1/22/2011 (1 year after first
intervention)
Now almost 1 year s/p OLT, doing well
without recurrence
56. YO
58 y/o male
Hepatitis B and C and HIV
Abdominal pain prompted CT
7 cm biopsy-proven HCC
Not a surgical or transplant candidate
Referred for locoregional therapy
57. MRI 1 month later –
100 mg doxorubicin on mass mostly
LC beads devascularized
58. Follow-up MRI –
Percutaneous complete necrosis, no
microwave ablation recurrence at 4 mos
59. TG
39 y/o female
Fibrolamellar HCC diagnosed in 2001
Left lobe resection of 9 x 11 cm mass in 2001
Recurrence 2007 with partial right lobe
resection
CT 4/9/2010: At least
Presents with multifocal recurrence 2/2010 10 hypervascular liver
masses
Not a surgical or transplant candidate
Presented at tumor board and referred for
locoregional therapy
60. TACE 5/3/2010 100 mg doxorubicin on
LC beads
2 weeks later, returns
with fevers, RUQ pain
61. CT 5/19/2010: near- complete
tumor necrosis
Prolonged CT 8/6/2010: Biloma
Percutaneous biloma catheter resolved, but
drainage drainage intrahepatic recurrence
and new lung nodule.
To study drug
62. August 2009 –
present 100 patients with HCC referred for
locoregional treatment
3 contraindicated for treatment
(bilirubin too high, extrehepatic
disease, hepatofugal flow)
3 insurance denials
13 did not receive 2 decided against treatment
1 awaiting treatment
locoregional treatment 1 direct to OLT
87 patients treated 1 referred for surgery
1 referred for Y-90
152 total procedures, mean 10 mo 1 died prior to treatment
follow-up
19 patients treated 66 patients treated 2 patients had
initially with RFA initially with TACE combo TACE/RFA
2 free of disease
12 2 2 3 8 15 7 10 18 8
Alive, disease Alive, brid Alive, with Dead Alive, dise Down- Alive, und Alive, brid Progressive Awaiting
-free ged to recurrence ase-free staged er ged to OLT disease follow up
OLT treatment
1 TACE 1 ALL
1 trial drug 1 asp PNA
1 OLT 2 13 4 6 8
rejection
Surgery RFA Extrahepatic Intrahepatic Dead
progression progression
1 awaiting 7 1 Nexavar 3 Y-90 7 liver cancer
surgery alive, diseas 3 Unknown 3 Nexavar 1 unknown
1 e-free cause
alive, diseas 1 alive, OLT
e-free 2 dead
3 alive with
recurrence
66. Treatment with TACE or RFA can downstage
tumors into Milan criteria
UCSF criteria for downstaging
• One lesion 5-8 cm
• 2-3 lesions up to 5 cm, total tumor diameter up to 8 cm
• 4-5 lesions up to 3 cm, total tumor diameter up to 8 cm
3 months after tumor is downstaged, exception
points for OLT are granted
• “Ablate and wait” crudely assesses tumor biology
Yao FY, Kerlan RK, Jr, Hirose R, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an
intention-to-treat analysis Hepatology 2008
67. Patients with tumors exceeding Milan do well with
transplant after downstaging
• Success of downstaging 24-90%
• If downstaging is successful, post-transplant 5-year survival
55-94%
Successful downstaging selects less aggressive
tumors
• Able to be downstaged
• Remains downstaged over a waiting period of 3-6 months
• Infiltrative tumors and high AFP predict downstage failure
Eligibility for downstaging is unclear
• Only tumors slightly beyond Milan?
• Any tumor without major vessel invasion or extrahepatic
disease?
Barakat O, et al. Morphological features of advanced hepatocellular carcinoma as a predictor of downstaging and liver transplantation: an intention-to-
treat analysis. Liver Transplantation 2010;16:289-299.
68. Systematic review of downstaging
for HCC beyond Milan criteria
8 studies, 720 patients
Successful downstaging 24-69%
3-year survival 79-100%
5-year survival
Barakat O, et al. Morphological features of advanced hepatocellular carcinoma as a predictor of downstaging and liver transplantation: an intention-to-
treat analysis. Liver Transplantation 2010;16:289-299.
69. “Downstaging with a subsequent interval
of observation to assess biologic
aggressiveness should be considered for
patients beyond Milan criteria.
Downstaged patients should be
considered for MELD exception points.”
Jarnagin W, et al. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB 2010;12:302-310.
70. Natural history of patients with
HCC within Milan criteria, at 1
year
• 70% will have tumor growth
• 20% will develop vascular invasion
• 9% will develop metastases
Risk of drop-out is up to:
• 11% at 6 months
• 57% at 12 months
• 75% at 18 months
Jarnagin W, et al. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB 2010;12:302-310.
71. 87 patients listed for OLT 52 patients listed for OLT
• 43 non-TACE and 22 TACE • Bridged with RFA
patients were comparable • Complete tumor necrosis in 85%
• TACE group had drop-off rate of • Drop-off rate of 6% at 1 year
3%
• Post-OLT survival of 76% at 3
• Non-TACE group had drop-off years, no HCC recurrence
rate of 15%
72. “Bridgingtherapy with TACE and RFA
have low morbidity, favorable HCC
response, and probably reduce drop-out
for patients with wait times >6 months”
Jarnagin W, et al. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB 2010;12:302-310.
73. “OLT is the preferred treatment for patients
with cirrhosis and HCC meeting Milan
criteria”
“OLTshould be considered on a highly
selective basis for patients beyond Milan
but within UCSF criteria”
Jarnagin W, et al. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB 2010;12:302-310.
75. Standard treatment for resectable HCC in
patients without cirrhosis
Only~5% of HCC patients in the Western
world qualify
Perioperative mortality rates
• Cirrhotic liver: 7-25%
• Non-cirrhotic liver: <3%
Jarnagin W, et al. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB 2010;12:302-310.
76. Advantages
• No restrictions on tumor size or number (within a lobe)
• Macrovascular invasion acceptable
• No obligatory waiting time
• Allows complete pathologic evaluation
Disadvantages
• Only feasible in non-cirrhotic or mildly cirrhotic livers without portal
hypertension
• Precancerous cirrhotic liver remains
• Perioperative mortality about 5%
• Significant post-operative morbidity
Jarnagin W, et al. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB 2010;12:302-310.
77. Overall 5-year survival for hepatic resection in HCC is 25-50%
• If solitary tumor and non-cirrhotic liver, 5-year survival is 41-74%
• If HCC is multifocal or has vascular invasion, 5-year survival is <25%
Liver function and portal hypertension are important predictors of
post-operative liver failure and 5-year survival
• Normal serum bilirubin and no portal HTN: 70%
• Normal serum bilirubin and portal HTN: 50%
• Elevated serum bilirubin and portal HTN: 30%
Post-resection recurrence rates are high
• 70% at 5 years
• >80% intrahepatic; usually due to dissemination from primary tumor
• Associated with high AFP, larger/more numerous tumors, and vascular invasion
Bruix J, Castells A, Bosch J, et al. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure.
Gastroenterology 1996;111(4):1018–22..
78. Liver resection is often limited due to inadequate
volume of the future liver remnant
• Normal patients can survive if 20% of liver volume
remains
• Post-chemotherapy patients need 30% of liver
• Patients with fibrosis/early cirrhosis need 40% of liver
Portal vein embolization can pre-operatively
enlarge the future liver remnant
• Redirection of nutrient-rich portal vein blood enlarges the
FLR
• May enable resection in patients who would otherwise not
be candidates
De Baere T, et al. Preoperative portal vein embolization: indications and technical considerations. Tech Vasc Interv Radiol 2007;10:67-78.
Memorial Sloan-Kettering Cancer Center. “Portal vein embolization.” Patient brochure, 2005.
79. Technical considerations
• Access ipsilateral (into tumor bearing lobe)
• 5F sheath and pigtail portogram; consider pressures
• Kumpe catheter and microcatheter for segment IV (if needed)
• Simmons-2 or Sos-2 catheter for right portal branches
• 100-700 micron Embospheres followed by coils; or NBCA
• Final portogram
• Embolize access tract with coils or gelfoam
Results at 4 weeks post-PVE
• 53-90% hypertrophy of FLR in normal liver
• 28-42% hypertrophy of FLR in cirrhotic liver
Complications
• Well-tolerated
• Occasional transient liver insufficiency in cirrhotics
• Poor technique can occlude entire PV
• If tumor is present in FLR, its growth may be more rapid
Madoff D, et al. Portal vein embolization with polyvinyl alcohol particles and coils in preparation for major liver resection for
hepatobiliary malignancy: safety and effectiveness- study in 26 patients. Radiology 2003;227:251-260.
De Baere T, et al. Preoperative portal vein embolization: indications and technical considerations. Tech Vasc Interv Radiol
2007;10:67-78.
80. “Resection with wide margins is the treatment of
choice for HCC in patients without cirrhosis”
“Resection is acceptable for cirrhotic patients
(Childs A without portal hypertension) with single
HCC, regardless of size.”
“Highly selected patients with multifocal HCC or
major vascular invasion may be resected, but
recurrence rates are high.”
Jarnagin W, et al. Surgical treatment of hepatocellular carcinoma: expert consensus statement. HPB 2010;12:302-310.
