Hepatocellular carcinoma is a leading cause of cancer death worldwide. Interventional radiologists play an important role in diagnosing and treating hepatocellular carcinoma. They can perform biopsies to determine disease, facilitate surgical treatment through techniques like portal vein embolization to increase eligibility for resection, and provide locoregional therapies for patients who are not surgical candidates like radiofrequency ablation, transarterial chemoembolization, and radioembolization. While offering palliation, these minimally invasive treatments can achieve local tumor control and prolong survival for some patients with hepatocellular carcinoma.

1. Hepatocellular
Carcinoma—Role
of Interventional
Radiologist
Dr. Muhammad Bin Zulfiqar
PGR IV FCPS Services Institute of Medical Sciences / Hospital
radiombz@gmail.com
Special Thanks to Anastasia Balius, MD Interventional Radiologist and RA & RSNA

2. Hepatocellular Carcinoma
• Approximately 24,120 persons diagnosed with liver
or intrahepatic bile duct cancer in the US in 20101
• 18,910 deaths from those cancers during that year1
• Incidence has risen significantly in developed
countries in the past two decades2
• Increased prevalence of hepatitis B and C
1American Cancer Society. Statistics last revised 7/7/10
2Ince N, Wands JR. The increasing incidence of heaptocellular carcinoma. N Engl J Med 1999;340:798-799.

3. Risk Factors
• Same as those for Cirrhosis
• Hepatitis B/C
• Excessive alcohol intake
• Inherited errors of metabolism
• Autoimmune hepatitis
• Non -alcoholic steatohepatitis [NASH]
• Environmental exposure to aflatoxin

4. Hepatocellular Carcinoma (HCC)
• With definitive treatment 5 year survival is over 50%1
• For all stages combined, 5 year survival is approximately
10%1
• Only 10-15% of patients are candidates for curative
therapy2,3
• Surgical resection
• Or transplant
1American Cancer Society. Statistics last revised 8/16/10
2Llovet JM. Treatment of hepatocellular carcinoma. Curr Treat Options Gastroenterol. 2004;7:431-441
3Kanematsu T, Furui J, Yanaga K, et al. A 16-year experience in performing hepatic resection in 303 patients with hepatocellular
carcinoma. J Vasc Interv Radiol 1995; 6:71–74.

5. Treatment of HCC
HCC
confirmed
•Multidisciplinary Evaluation
•H+P
•Hepatitis Panel
•Bilirubin, transaminases,
alk phos, LDH
•PT /INR, albumin, protein,
BUN, Cr
•CBC, platelets
•AFP
•Chest imaging
•Bone scan as indicated
Potentially resectable or
transplantable, operable
by performace status or
comorbidity
Unresectable
Inoperable by
performance status or
comorbidity, local
disease only
Metastatic disease

6. Treatment of HCC
• For patients with an estimated FLR / total liver volume ratio
below recommended values who are otherwise suitable
candidates for liver resection, pre-operative portal vein
embolization (PVE) should be considered
NCCN Practice Guidelines in Oncology – v.2.2011, Hepatobiliary Cancers.
FLV---Future liver ramnant

7. Treatment of HCC
Potentially
resectable or
transplantable
•Child’s A, B
•No portal hypertension
•Suitable tumor location
•Adequate liver reserve
•Suitable liver remnant
•UNOS criteria
•Patient has a tumor <5 cm in dm or 2-
3 tumors < 3 cm each
•No macrovascular involvement
•No extrahepatic disease
•These patients may be resected if
transplantation not feasible
Resection, if
feasible
(preferred)
or locoregional
therapy
Liver
Transplant
Clinical presentation Surgical Assessment Treatment

8. Child-Pugh Score
1 2 3
Encephalopathy (grade) None 1-2 3-4
Ascites None Slight Moderate
Albumin (g/dL) >3.5 2.8-3.5 <2.8
Prothrombin time
Prolonged (sec)
1-4 4-6 >6
Bilirubin (mg/dL)
- for primary biliary
cirrhosis
1-2
1-4
2-3
4-10
>3
>10
Clinical/Biochemical Parameters Points for Increasing Abnormality
Class A = 5-6 points; Class B = 7 -9 points; Class C = 10-15 points

9. Treatment of HCC
Inoperable by performance
status or comorbity, local
disease only
Metastatic disease
Clinical Presentation Treatment
Options:
Sorafenib (Child-Pugh Class A [Category 1] or B)
Clinical Trial
Locoregional Therapy
RT (conformal or sterotactic) (category 2B)
Supportive Care
Sorafenib (Child-Pugh Class A [Category 1] or B)
Or
Supportive Care
Or
Clinical trial

10. Loco-regional Therapy
Ablation
• Tumor and margin of
normal tissue should be
treated
• Tumors < 3 cm; lesions
between 3-5 cm should be
treated in combination with
embolization
Embolization
• Arterial blood supply to the
tumor must be able to be
isolated without non-target
embolization
• Relatively contraindicated
with bilirubin >3 mg/dL
• Contraindicated with main
PV thrombosis (relative) or
Child-Pugh Class C
(absolute)

11. Treatment of HCC
Unresectable
•Inadequate
hepatic
reserve
•Tumor
location
Extensive
liver tumor
burden
Meets
UNOS
criteria?
Transplant
Not a transplant
candidate
Options:
Sorafenib (Child-Pugh Class A [Category 1] or B)
Chemotherapy + RT only in the context of a clinical
trial
Clinical trial
Locoregional therapy
RT (conformal or sterotactic) (category 2B)
Supportive care
Systemic or intra-arterial chemotherapy in clinical
trial

12. Metastatic Colorectal Cancer (mCRC)
• 5 year survival for stage IV colorectal cancer is 6%1
• Liver is most frequent site of metastases
• Approximately 60% of patients with mCRC will eventually
have liver as predominant site of disease2
• Surgical resection is treatment of choice
• 5 year survival rates after resection >50%3,4
• Feasible in <20% of patients2
1American Cancer Society. Statistics last revised 3/2/2011
2Sasson AR, Sigurdson ER. Surgical treatment of liver metastases. Semin Oncol. 2002;29:107-118
3Choti MA, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg. 2002;235:759-766.
4Pawlik TM, et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg.
2005;241:715-722, discussion 722-714.

13. Treatment of mCRC
When hepatic disease is not optimally resectable based on insufficient remnant
liver volume, approaches utilizing preoperative portal vein embolization1 or
staged liver resection can be considered
NCCN Practice Guidelines in Oncology – v.3.2011, Colon Cancer
mCRC—Metastatic colorectal cancer
1Covey AM, et al. Combined portal vein embolization and neoadjuvant chemotherapy as a treatment strategy for
resectable hepatic colorectal metastases. Ann Surg. 2008 Mar;247(3):451-5.

14. Treatment of mCRC
• Ablative techniques may be considered alone or in
conjunction with resection. All original sites of
disease need to be amenable to ablation or resection.
• Some institutions use arterially directed embolic
therapy in highly select patients with chemotherapy
resistant/refractory disease without obvious systemic
disease, with predominent hepatic metastases
(category 3)

15. Role of Interventional Radiology
1. Supportive procedures for the oncology
patient
2. Determination of disease
3. Facilitation of definitive surgical treatment
4. Treatment of non-surgical candidates

17. Determination of Disease
• AFP and ultrasound are used as screening for HCC
• Additional imaging is indicated in the setting of a rising serum
AFP or identification of a liver mass nodule on US

18. Determination of Disease
• Three different modalities
• Triphasic helical CT
• Triphasic dynamic contrast enhanced MRI
• Contrast enhanced U/S

19. Determination of Disease
• Nodules 1 to 2 cm in size need to demonstrate classic arterial
enhancement with two different diagnostic techniques
• Nodules > 2 cm need demonstrate classic arterial
enhancement with only one diagnostic technique
• Nodules < 1 cm should be re-evaluated every 3 to 4 months
until fit into a size criteria
• If nodules are non-diagnostic on imaging, tissue sampling is
needed

20. Facilitation of Definitive Surgical Treatment
Portal Vein Embolization
Transplant “Bridge”

21. Portal Vein Embolization (PVE)
• In primary or secondary hepatic malignancy, extended
hepatectomies provide a chance of cure1
• Morbidity and mortality of such procedures are considerable2
• Volume and function of the liver remnant is a major risk factor
for perioperative complications3,4
1Vauthey JN, et al. Is extended hepatectomy for hepatobiliary malignancy justified? Annals of Surgery. 2004 May; 239(5):722-
30; discussion 30-2
2Jarnagin WR, et al. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the
past decade. Annals of Surgery. 2002 Oct;236(4):397-406; discussion-7..
3Abdalla EK, et al. Extended hepatectomy in patients with hepatobiliary malignancies with and without preoperative portal vein
embolization. Arch Surg. 2002 Jun:137(6):675-80; discussion 80-1
4Vauthey JN, et al. Standardized measurement of the future liver remnant prior to extended liver resection: methodology and
clinical associations. Surgery. 2000 May;127(5):512-9

22. Portal Vein Embolization
• PVE induces hypertrophy in the non-embolized liver segments
• Increase in volume and function of future liver remnant (FLR)
• Decreases risk of post-operative hepatic insufficiency
Abdalla EK, et al. Portal vein embolization: rationale, technique and future
prospects. The British Journal of Surgery. 2001 Feb;88(2):165-75
Makuuchi M, et al. Preoperative portal embolization to increase safety of major
hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery. 1990
May;107(5):521-7

23. PVE
• Normal underlying liver1
• FLR should be 20-25% of total liver volume (TLV)
• Chemotherapy induced liver injury2
• FLR should be >30% of TLV
• Chronic liver disease (cirrhosis or severe fibrosis)2
• FLR should be >40%
1Abdalla EK, et al. Extended hepatectomy in patients with hepatobiliary malignancies with and without
preoperative portal vein embolization. Arch Surg. 2002 Jun;137(6):675-80; discussion 80-1.
2Azoulay D, et al. Percutaneous portal vein embolization increases the feasibility and safety of major
liver resection for hepatocellular carcinoma in injured liver. Annals of Surgery. 2000 Nov;232(5):1176-
81.

24. PVE Contraindications
• Extra-hepatic metastases
• Overt portal hypertension
• Tumor invasion of the portal vein
• Tumor invasion of the FLR
• Biliary obstruction
• Renal insufficiency
• Uncorrectable coagulopathy

25. Couinaud Classification

26. Hepatic Anatomy

27. Hepatic Anatomy

28. PVE
• Performed under conscious sedation
• 2 standard approaches
• Percutaneous ipsilateral
• Percutaneous contralateral
• Wide array of embolic agents
• Coils, amplatzer plugs
• Particles
• Absolute alcohol
• Fibrin glue
• N-BCA (n-butyl cyanoacrylate)

31. Complications
• Bleeding (0.2 – 1/6%)
• Pneumothorax
• Sepsis
• Liver abscess (0.3%)
• Portal hypertension
resulting in esophageal
variceal hemorrhage
Di Stefano DR, et al. Preoperative percutaneous portal vein embolization: evaluation of adverse
events in 188 patients. Radiology. 1993 Jul;188(1):73-7
Kodama Y, et al. Complications of percutaneous transhepatic portal vein embolization. J Vasc
Interv Radiol. 2002 Dec;13(12):1233-7
• Migration of embolic
material (0.2-5.3%)
• Portal vein thrombosis of
FLR (<1%)
• Portal vein dissection
• Intra-parenchymal injury
• Transient liver failure
(3.2%)

32. Outcomes
• Average expected growth of FLR = 8-27%1
• 75% of growth occurs in first 3 weeks post-PVE2
• Failure to hypertrophy >5% following PVE is associated
with a significantly higher risk of major complications,
hepatic insufficiency, and increased 90-day mortality2
1Abulkhir A, et al. Preoperative portal vein embolization for major liver resection: a meta-analysis. Ann Surg. 2008
Jan;247(1):49-57
2Ribero D, et al. Portal vein embolization before major hepatectomy and its effects on regeneration, resectability, and
outcome. The British Journal of Surgery. 2007 Nov;94(11): 1386-94

33. Facilitation of Definitive Surgical Treatment
• Locoregional treatment of HCC as a “bridge” to liver
transplantation1,2
• Radiofrequency ablation3,4
• Chemoembolization5
• Radioembolization
1Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208-1236
2Llover JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008;100:698-711.
3Pompili M, et al. Percutaneous ablation procedures in cirrhotic patients with hepatocellular carcinoma submitted for liver
transplantation: assessment of efficacy at explant analysis and of safety for tumor recurrence. Liver Transpl. 2005;11:1117-
1126.
4Mazzaferro V, et al. Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver
transplantation: a prospective study. Ann Surg. 2004;240:900-909.
5Richard HM, 3rd, et al. Hepatic arterial complications in liver transplant recipients treated with pretransplantation
chemoembolization for hepatocellular carcinoma. Radiology. 2000;214:775-779.

34. Treatment of Nonsurgical Candidates
• Ablative techniques
• Radiofrequency ablation
• Microwave ablation
• Alcohol ablation
• Arterial embolization
• Trans-arterial embolization (TAE)
• Trans-arterial chemoembolization (TACE)
• Trans-arterial radioembolization or Selective Internal
Radiation Therapy (SIRT)
• Combination therapy

35. Patient Work-up
• Laboratory studies
• CBC, Chem 7, PT/PTT, liver function tests, tumor markers
• Cross-sectional imaging (CT/MRI)
• Childs class
• Performance status
• ECOG / Karnofsky
• Staging
• Consent with emphasis on palliation and management of expectations

36. Alcohol versus RFA
• RFA was shown to be superior to PEI with respect to complete
response rate1
• RFA demostrated a lower rate of recurrence2,3
• Overall survival higher for RFA2,3
• Fewer treatment sessions for RFA3
1Brunello F, et al. Radiofrequency ablation versus ethanol injection for early hepatocellular carcinoma: A
randomized controlled trial. Scand J Gastroenterol. 2008;43:727-735
2Lin SM, et al. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular
carcinoma <4 cm. Gastroenterology. 2004;127:1714-1723
3Shiina S, et al. A randomized controlled trial of radiofrequency ablation with ethanol injection for small
hepatocellular carcinoma. Gastroenterology. 2005;129:122-130.

37. RFA vs. Ethanol Injection
Author Treatment Complete
Resonse
2-yr local
progression
2 yr 3 yr P
Lencioni ,
20031
PEI (n=50) 82% 38%* 88% NA
RFA (n=52) 95% 4%* 96% NA NS
Lin, 20042 PEI, low dose
(n=52)
88% 45% 61% 50%
PEI, high dose
(n=52)
92% 33% 63% 55%
RFA (n=52) 96% 18% 82% 74% <.05
Shiina,
20053
PEI (n=114) 100% 11% 82% 63%
RFA (n=118) 100% 2% 90% 80% <.05
1Lencioni R, et al. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radiofrequency ablation versus percutaneous ethanol injection. Radiology 2003;228:235-240.
2Lin SM, et al. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or = 4 cm. Gastroenterology 2004;127:1714-1723.
3Shiina S, et al. A randomized controlled trial of radiofrequency ablation versus ethanol injection for small hepatocellular carcinoma. Gastroenterology. 2005;129:122-130.
Survival rate

38. 18
Local recurrence rates for HCC
• More recent study found <3% of patients with single HCC
tumor < 2 cm had recurrent disease at 31 months after
repeated application of RFA1
1Livraghi T, et al. Sustained complete response and complications rates after radiofrequency ablation
of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice?
Hepatology. 2008;47:82-89.

39. Long-Term Survival
Author and Year Patient Characteristics Pt # 1 yr 3 yr 5 yr
Lencioni, 2005 Child A, 1 HCC <5cm or 3 <3cm 144 100 76 51
Child A, 1 HCC <5 cm 116 100 89 61
Child B, 1 HCC <5 cm or 3 <3 cm 43 89 46 31
Tateishi, 2005 Naive patients 319 95 78 54
Non-naïve patients 345 92 62 38
Cabassa, 2006 59 94 65 43
Choi, 2007 Child A, 1 HCC <5cm or 3 <3 cm 359 NA 78 64
Child B, 1 HCC <5cm or 3 <3 cm 160 NA 49 38
Survival Rate (%)
Lencioni R, et al. Early-stage hepatocellular carcinoma in cirrhosis: long-term results of percutaneous image-guided
radiofrequency ablation. Radiology 2005;234:961-967
Tateishi R, et al. Percutaneous radiofrequency ablation for hepatocellular carcinoma. Cancer 2005;103:1201-1209
Cabassa P, et al. Radiofrequency ablation of hepatocellular carcinoma: long-term experience with expandable needle
electrodes. AJR 2006;185:S316-321
Choi D, et al. Percutaneous radiofrequency ablation for early-stage hepatocellular carcinoma as a first-line treatment:
long-term results and prognostic factors in a large singe-institution series. Eur Radiol 2007;17:684-692.

40. Radiofrequency Ablation vs. Resection
• RFA compared to liver resection in a prospective randomized
controlled study
• Patients with solitary HCC <5 cm in diameter
• No differences in recurrence-free survival or overall survival
were found when treatment arms were compared.
Chen MS, et al. A prospective randomized trial comparing percutaneous
local ablative therapy and partial hepatectomy for small hepatocellular
carcinoma. Ann Surg. 2006;243:321-328.

41. Microwave Ablation
• In moderately or poorly differentiated HCC, overall survival
was significantly better than with PEI1
• In study of 234 pts, 3 yr and 5 yr survival rates were 73% and
57%2
• In the one randomized trial comparing microwave and
radiofrequency ablation, no statistically significant differences
were observed in the efficacy of the two techniques3
1Seki T, et al. Percutaneous microwave coagulation therapy for patients with small hepatocellular carcinoma: comparison with
percutaneous ethanol therapy. Cancer 1999;85:1694-1702
2Dong B, et al. Percutaneous sonographically guided microwave coagulation therapy for hepatocellular carcinoma: results in 234
patients. AJR 2003;180:1547-1541.
3Shibata T, et al. Small hepatocellular carcinoma: comparison of radio-frequency ablation and percutaneous microwave
coagulation therapy. Radiology 2002;223:331-337.

42. RFA for mCRC
Author Patients Metastases Size (cm) Local contol Survival
Solbiati
20011
117 179 0.9-9.6; 61% 3 yr: 46%
Gillams
20042
167 354 1-12; mean,
3.9
74.9% 5 yr: 26%
Jakobs
20063
68 183 0.5-5.0;
mean, 2.2
82% 3 yr: 68%
Lencioni
20054
423 543 0.5-5.0;
mean 2.7
85.4% 3 yr: 47%
5 yr: 24%
Sorensen
20075
102 332 3 yr: 64%
5 yr: 44%
1Solbiati L, et al. Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117
patients. Radiology 2001 Oct;221(1):159-66.
2Gillams AR, Lees WR. Radio-frequency ablation of colorectal metastases in 167 patients. Eur Radiol 2004;14:2261-2267.
3Jakobs TF, et al. Radiofrequency ablation of colorectal liver metastases: mid-term results in 68 patients. Anti-cancer Res
2006;26:671-680.
4Lencioni R, et al. Percutaneous radiofrequency ablation of hepatic colorectal metastases: technique, indications, results and new
promises. Invest Radiol 2004;39:689-697.
5Sorensen SM, et al. Radiofrequency ablation of colorectal liver metastases: long-term survival. Acta Radiol 2007;48:253-258.

43. RFA versus resection of mCRC
• A number of retrospective studies have compared RFA and
liver resection in the tx of liver mets1-3, although RFA has not
been well studied in this setting
• In retrospective studies comparing RFA and liver resection in
liver mets RFA has been inferior to resection with respect to
rates of local recurrence and 5-year overall survival4
• Patient selection bias, technological limitations of RFA or
both?2
1Hur H, et al. Comparative study of resection and radiofrequency ablation in the treatment of solitary colorectal liver metastases. Amer
J Surg. 2009;197:728-736.
2Gleisner AL, et al. Colorectal liver metastases: recurrence and survival following hepatic resection, radiofrequency ablation, and
combined resection-radiofrequency ablation. Arch Surg. 2008;143:1204-1212.
3Reuter NP, et al. Radiofrequency ablation vs. resection for hepatic colorectal metastasis: therapeutically equivalent? J Gastrointest
Surg. 2009;13:486-91.
4Abdalla EK. Commentary: Radiofrequency ablation for colorectal liver metastases: do not blame the biology when it is the technology.
Amer J Surg. 2009;197:737-739.

44. Radiofrequency Ablation
• Electrode probes deliver an alternating high-frequency
electrical current (460 to 500 kHz)
• Ion agitation is converted by friction into heat
• Tissue temperature is increased
• Cellular death occurs via thermal coagulation necrosis

45. Technique
• Re-identify lesion under CT or US
• Choose appropriate access site
• Plan approach
• Place probes
• 12 to 16 minute ablation
• Tract ablation

46. Considerations
• “Heat sink” effects
• Compromised sphincter of Oddi
• Levaquin and flagyl prep
• Adjacent structures
• Diaphragm
• Abdominal wall
• Capsule
• Bowel
• Size

47. Development of Ablated Region
• After 24 to 48 hours, necrotic lesion forms reaching maximum
size by 7 days
• Ablated lesion may exhibit an increase in size up to 3 months
post ablation1
• Ablated tissue will be replaced by scar or reabsorbed
• Treated area will not enhance on follow up imaging2
• Most residual viable tumor is evident at 1-3 months after
ablation3
1McDougal WS, et al; J Urol 2005; 174:61-63
2Kawamoto, et al; Radiographics 2007; 27:343-355
3Gervais, et al; AJR 2005; 185:64-71

48. Complications
• Hemorrhage1
• Hemoperitoneum
• Hemothorax
• Hemobilia
• Pneumo/Hydrothorax
• Abscess
• Sepsis
• Liver Failure2
• Tumor seeding
• Skin Burn
• Damage to surrounding
structures
• Pain in a dermatomal/
diaphragmatic
distribution
• Post ablation syndrome
1Goto E et al. J Clin Gastroenterol 2009 Oct 3 [Epub ahead of print}
2Kong WT, et al. World J Gastroenterol 2009 Jun 7; 15(21):2651-6

49. Complication Rate
• Mortality rate ranges from 0.1% to 0.5%
• Most common causes of death were sepsis and hepatic failure
• Major complication rate ranges from 2.2% to 3.1%
• Minor complication rate ranges from 5% to 8.9%
• Most common complications were intraperitoneal bleeding, hepatic
abscess, bile duct injury, hepatic decompensation, and grounding pad
burns
Rhim H. Complications of radiofrequency ablation in hepatocellular carcinoma. Abdom Imaging 2005 Jul-Aug; 30 (4): 409-18
Livraghi T, et al. Treatment of focal liver tumors with percutaneous radiofrequency ablation: complications encountered in a multicenter
study. Radiology 2003;26:441-451.
De Baere T, et al. Adverse events during radiofrequency treatment of 582 hepatic tumors. AJR 2003;181:695-700.
Bleicher RJ, et al. Radiofrequency ablation in 447 complex unresectable liver tumors: lessions learned. Ann Surg Oncol 2003;10:52-
58.

50. Tumor seeding
• Uncommon late complication
• Subcapsular location and poor degree of differentiation seem to be at a higher
risk1
• Incidence of 0.5% in HCC patients in both a multicenter and single institution
series2,3
• Tract ablation used routinely to prevent
1Llovet JM, et al. Barcelona Clinic Liver Cancer (BCLC) Group. Increased risk of tumor seeding after percutaneous
radiofrequency ablation for single hepatocellular carcinoma. Hepatology 2001;33:1124-1129.
2Livraghi T, et al. Treatment of focal liver tumors with percutaneous radiofrequency ablation: complications
encountered in a multicenter study. Radiology 2003;26:441-451.
3Lencioni R, et al. Early-stage hepatocellular carcinoma in cirrhosis: long-term results of percutaneous image-
guided radiofrequency ablation. Radiology 2005;234:961-967.

51. Post RFA Syndrome
• Analagous to post embolization syndrome
• Defined as low grade fever and flu-like symptoms within the
first 24-48 hours lasting approximately one week
• Fever usually peaks on day 3
• Flu-like symptoms peak on day 5
1Llovet JM, et al. Barcelona Clinic Liver Cancer (BCLC) Group. Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular
carcinoma. Hepatology 2001;33:1124-1129.
2Livraghi T, et al. Treatment of focal liver tumors with percutaneous radiofrequency ablation: complications encountered in a multicenter study. Radiology 2003;26:441-
451.
3Lencioni R, et al. Early-stage hepatocellular carcinoma in cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation. Radiology 2005;234:961-967.

52. Post RFA Syndrome
• Incidence of 37% in liver ablation
• 95% of patients had symptoms but not complete syndrome
• Size of treated lesion doesn’t correlate with incidence or
severity
• Number of ablations (>3) correlates with increased symptoms
15
Wah, et al; Radiology 2005; 237:1097-1102

53. Overall RFA Complication Rates
Tissue # patients Complications Mortality rates
Liver 2300 [1]
382 [2]
2.2%
8%
0.3%
0.1%
Kidney 54 sessions [3] 7% 0%
Bone 43 [4] 7% 0%
Lung 26 [5] 10% 0%
1. Livraghi T et al. Treatment of Focal Liver Tumors with Percutaneous Radiofrequency Ablation: complications encountered in a multicenter study.
Radiology 2003; 226: 441-451
2. Curley S et al. Early and late Complications after Radiofrequency Ablation of malignant Liver Tumors in 608 Patients. Annals of Surgery, Vol 239,
No4 April 2004
3. Gervais DA et al, renal Cell Carcinoma: Clinical Experience and Technical Success with Radio-frequency Ablation of 42 tumors. Vascular and
Interventional Radiology
4. Goetz et al. Percutaneous image-guided radiofrequency ablation of painful metastases involving bone: a multi center study. J Clin Oncol. 2004 Jan
15;22 (2):300-6
5. Lee et al. Percutaneous Radiofrequency Ablation for inoperable NSC Lung Cancer and matastases: Preliminary report. Radiology, January 2004

54. Follow-up imaging
HCC
• Contrasted CT or MRI in 1
month
• CT/MRI every 3 months
until one year
• Enhancement in HCC pt =
residual
disease/recurrence
mCRC
• Contrasted CT or MRI in 1
month to detect new
lesions
• CT/MRI every 3 months
with tumor markers
• PET may be useful in
detecting residual tumor or
relapse1,2,3
Post ablation hypoattenuation is greater than original lesion initially, then a
decrease in size will be seen
1Akhurst T, et al. Positron emission tomography imaging of colorectal cancer. Semin Oncol 1999;26:577-583
2Fong Y, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001
consecutive cases. Ann Surg 1999;230:309-321
3Anderson GS, et al. FCG positron emission tomography in the surveillance of hepatic tumors treated with radiofrequency ablation. Clin
Nucl Med 2003;28*:192-197

55. Intra-arterial therapy HCC
• The panel recommends that patients with
unresectable/inoperable disease who are eligible to
undergo embolization therapy and have tumor lesions
> 5 cm should be treated using arterial embolic
approaches (chemoembolization, bland embolization,
radioembolization)
• Those patients with lesions 3-5 cm can be considered
for combination therapy with ablation and arterial
embolization
NCCN Practice Guidelines in Oncology – v.1.2011, Hepatobiliary Cancers

56. Intra-arterial Therapy mCRC
• Arterially-directed embolic therapy is considered category 3
• Specifically, highly select patients with chemotherapy
resistant/refractory disease, without obvious systemic disease,
with predominant hepatic metastases
• Radioembolization with yttrium-90 microspheres is the only
technique specifically mentioned
NCCN Practice Guidelines in Oncology – v.3.2011, Colon Cancer

57. Intra-arterial Therapy Options

58. Catheter is
placed via a
transfemoral
approach with
tip within the
selected
hepatic artery

59. Intra-arterial administration exploits the
dual blood supply of the liver
• Tumors receive 80-100%
of their blood supply from
hepatic artery
• Normal liver receives >
75% of its blood supply
from portal vein
Breedis C, Young G. The blood supply of neoplasms in the liver. Am J Pathol. 1954;30:969-977.

60. Bland Embolization of HCC
• Retrospective analysis
• 1-, 2-, and 3-year survival rates of 66%, 46%, and 33% were
observed
• Survival rates increased to 84%, 66% and 51% when only the
subgroup of patients w/o extrahepatic spread or portal vein
involvement by tumor was considered1
1Maluccio MA, et al. Transcatheter arterial embolization with only particles for the treatment of unresectable
hepatocellular carcinoma. J Vasc Interv Radiol. 2008;19:862-869

61. Bland Embolization of HCC
• Predictors of poor prognosis on multivariate analysis
• Tumor size >5 cm
• 5 or more tumors
• Extrahepatic disease
• Portal vein occlusion was not found to be an independent
predictor of survival
Maluccio MA, et al. Transcatheter arterial embolization with only particles for the treatment of unresectable
hepatocellular carcinoma. J Vasc Interv Radiol. 2008;19:862-869

62. Bland vs. Chemo-embolization of HCC
• Only one study directly comparing the two therapies
• Pt randomized to TAE, TACE, supportive care
• This was stopped early when a demonstrable benefit was
shown between chemoembolization and supportive care arms
• Due to early termination, lack of power to detect a difference
in TACE and TAE
Llovet JM, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable
hepatocellular carcinoma: a randomixed controlled trial. Lancet 2002;359((9319):1734-9.

63. Chemoembolization of HCC
• 112 patients with
unresectable HCC
• 85% had hepatitis C
• Randomized to
blandembolization,
chemoembolizaiton, or
conservative management
• Primary endpoint was
survival
Hong Kong (Single Center) Study2
• 80 patients with
unresectable HCC
• 80% had hepatitis B
• Randomized to
chemoembolization or
conservative management
• Primary endpoint was
survival
1Llovet JM, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with
unresectable hepatocellular carcinoma: a randomixed controlled trial. Lancet 2002;359((9319):1734-9.
2Lo CM, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable
hepatocellular carcinoma. Hepatology 2002;35(5):1164-71
Barcelona Multicenter Study1

64. Chemoembolization of HCC
• Survival in CE group
1 yr = 82%
2 yr = 63%
• Survival in bland
embolization group
1 yr = 75%
2 yr = 50%
• Survival in conservative
therapy group
1 yr = 63%
2 yr = 27%
Hong Kong Study
• Survival in CE group
1 yr = 57%
2 yr = 31%
• Survival in conservative
therapy group
1 yr = 32%
2 yr = 11%
Barcelona Study

65. Chemoembolization of HCC
• In both studies, patients in the chemoembolization group
were half as likely to die during the trial than patients in the
conservative therapy group
• For the Barcelona study:
• OR = 0.45
• 95% CI 0.25 – 0.81
• For the Hong Kong study:
• OR = 0.5
• 95% CI 0.31 – 0.81

66. Chemoembolization of HCC
• Survival rates in both the CE and control groups were lower in
the Hong Kong study than in the Barcelona study
• Higher proportion of Okunda stage II disease
• Patients with portal vein invasion not excluded

67. Chemoembolization of HCC
• Only independent predictor of survival was treatment
allocation1
• Benefit of chemoembolization was independent of tumor size,
stage or presenting symptom2
• When portal vein invasion present, however, no benefit to
chemoembolization seen
1Llovet JM, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with
unresectable hepatocellular carcinoma: a randomixed controlled trial. Lancet 2002;359((9319):1734-9.
2Lo CM, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable
hepatocellular carcinoma. Hepatology 2002;35(5):1164-71

68. Bland/Chemo-embolization of mCRC
Randomized study comparing TAE with TACE demonstrated no
advantage of one technique over the other
Salman HS, et al. Randomized phase II trial of embolization therapy versus
chemoembolization therapy in previously treated patients with colorectal carcinoma
metastatic to the liver. Clin Colorectal Cancer 2002;2:173-179.

69. Drug eluting beads in HCC
• Objective response rate by imaging (EASL criteria) ranged from
60 to 90%1,2
• Survival rates appear improved over those with conventional
TACE3
• 93% at 6 months to 89% at 2 years1,2
• Significantly lower serum levels of chemotherapy drug4
1Kettenbach J, et al. Drug-loaded microspheres for the treatment of liver cancer: review of current results. Cardiovasc Intervent Radiol 2008;31:468-
476.
2Malagari K, et al. Transarterial chemoembolization of unresectable heptaocellular carcinoma with drug eluting beads: Results of an open-label study
of 62 patients. Cardiovasc Intervent Radiol 2008;31:269-280.
3Dhanasekaran R, et al. Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting
beads (DEB) for unresectable hepatocelluar carcinoma (HCC) J. Surg. Oncol. 2010; 101:476-480
4Varela M, et al. Chemoembolization of Hepatocellular carcinoma with drug eluting beads: Efficacy and doxorubicin pharmcokinetics. J Hepatol
2007;46:747-787.

71. DEB for mCRC
• In study of 55 patients, survival rate of 78% at 18 months1
• Patients thought to have less side effects from the beads than
from traditional TACE
• Easier to infuse
• More study is needed
1Martin RCG, et al. Transarterial chemoembolisation (TACE) using irinotecan-loaded beads for the
treatment of unresectable metastases to the liver in patients with colorectal cancer: an interim report. World
Journal of Surgical Oncology 2009, 7:80

72. Chemoembolization Pt Selection
• Is patient eligible for hepatic resection?
• Is patient eligible for ablation?
• Liver dominant disease
• Hepatocellular carcinoma
• Metastatic colorectal carcinoma
• Intrahepatic cholangiocarcinoma
• Metastatic neuroendocrine tumors
• Rarely, ocular melanoma, sarcoma, pancreas, breast, lung

73. Chemoembolization Work-up
• Cross-sectional imaging (MR/CT)
• Assessment of performance status (ECOG or Karnofsky)
• Childs class
• Tumor stage
• Laboratory studies (CBC, Chem 7, PT/PTT, liver function tests,
tumor markers)

74. Relative Contraindications
• Biliary obstruction
• High risk of infection of obstructed segments1
• Without intact sphincter of Oddi
• Increased risk of abscess2
• Portal vein occlusion
• Liver infarction
• Elevated bilirubin
• Liver failure
11Song SY, et al. Liver abscess after transcatheter oily chemoembolization for hepatic tumors: incidence, predisposing factors
and clinical outcome. J Vasc Interv Radiol 2001;12:313-320.
2Kim W, Clark TWI, Baum RA, et al. Risk factors for liver abscess formation after hepatic chemoembolization. J Vasc Interv
Radiol 2001; 12:965–968.

75. Relative Contraindications
• Biliary obstruction
• Percutaneous catheter drainage1
• Without intact sphincter of Oddi
• Night before bowel prep and prophylactic antibiotics2
• Portal vein occlusion
• Segmental or subsegmental embolization
• Limit chemotherapy3
• Document sufficient hepatic collaterol flow4
• Elevated bilirubin
• Superselective embolization
1Song SY, et al. Liver abscess after transcatheter oily chemoembolization for hepatic tumors: incidence, predisposing factors and
clinical outcome. J Vasc Interv Radiol 2001;12:313-320.
2Geschwind JF, Kaushik S, Ramsey DE, et al. Influence of a new prophylactic antibiotic therapy on the incidence of liver abscesses
after chemoembolization treatment of liver tumors. J Vasc Interv Radiol 2002; 13:1163–1166.
3Kiely JM, et al. Chemoembolization in patients at high risk: results and complications. J Vasc Interv Radiol 2006;17:47-53.
4Pentecost MJ, et al. Hepatic chemoembolization: safety with portal vein thrombosis. J Vasc Interv Radiol 1993;4:347-351.

76. Prep for Sphincter of Oddi dysfunction
• Oral Levaquin 500 mg daily two days before and for seven
days following the procedure
• Oral Flagyl 500 mg twice daily two days before and for seven
days following the procedure

77. High risk of acute hepatic failure and post
procedural mortality post TACE
• >50% of liver volume
replaced by tumor
• LDH >425 IU/L
• AST (SGOT) > 100 IU/L
• Bilirubin >2 mg/dL
• Individual abnormalities of
these four parameters
have not been shown to
predict adverse outcomes
of chemoembolization
Charnsangavej, C. Chemoembolization of liver tumors.
Semin Invest Radiol 1993;10:150-160.
Berger DH, Carrasco CH, Hohn DC, et al. Hepatic artery
chemoembolization or embolization for primary and
metastatic liver tumors: post-treatment management and
complications. J Surg Oncol 1995; 60:116 –121.
Brown DB, Fundakowski CE, Lisker-
Melman M, et al. Comparison of
MELD and Child-Pugh scores to predict
survival after chemoembolization
for hepatocellular carcinoma. J Vasc Interv
Radiol 2004; 15:1209 –1218.

78. Side effects
• Post embolization syndrome in 80-90% of patients
• Pain, fever, nausea, vomiting
• Severity varies
• PCA and liberal use of antiemetics as well as good pre-
procedure medication regimen
Leung DA, Goin JE, Sickles C, et al. Determinants of postembolization syndrome after hepatic chemoembolization.
J Vasc Interv Radiol 2001; 12:321–326.

79. Complications
Serious event = 3-7%
• Hepatic
insufficiency/infarction
• Hepatic abscess
• Tumor rupture
• Chemical cholecystitis
• Non-target embolization to
the bowel
Other complications (<1%
incidence each)
• Renal insufficiency
• anemia
30 day mortality
ranges from 1 – 4%
Sakamoto I, et al. Complications associated with transcatheter embolization for hepatic tumors. Radiographics 1998;18:605-619
Gates J, et al. Chemoembolization of hepatic neoplasms: safety, complications and when to worry. Radiographics 1999;19:399-
414.

80. Major complications
Specific Major Complication Reported Rate (%))
Liver failure 2.3
Abscess with functional sphincter of Oddi <1
Post-embolization syndrome requiring extended stay
or readmission
4.6
Abscess with biliary-enteric anastamosis/biliary
stent/sphincterotomy
25
Surgical cholecystitis <1
Biloma requiring perutaneous drainage <1
Pulmonary arterial oil embolus <1
Gastrointestinal hemorrhage/ulceration <1
Iatrogenic dissection preventing treatemtn <1
Death within 30 days 1
Daniel B. Brown, et al. Quality Improvement Guidelines for Transhepatic Arterial Chemoembolization, Embolization, and
Chemotherapeutic Infusion for Hepatic Malignancy. J Vasc Interv Radiology July 2009 ;20(7) Supplement:S219-
S226.e10

81. Pre-procedure orders
• IV normal saline 500 cc bolus then 200cc/hr
• Rocephin 1 gm IV
• Diphenhydramine 50 mg IV
• Dexamethazone 10 mg IV
• Ondansetron 24 mg IV
• Pepcid 20 mg IV
• Dilaudid PCA

82. Post procedure orders
• Patient controlled anesthesia
• Ondansetron 8 mg q8h IV, PRN nausea
• Tylenol 650 mg q4h po, PRN fever
• Augmentin 875mg one PO BID x seven days. or if allergic to
PCN: Cipro 500mg one PO bid x seven days.

83. Follow up
• Labs in three weeks to assess for continued eligibility
• Repeat CT or repeat treatment in 4 weeks
Discharge
• Augmentin or Ciprofloxacin
• Fevers < 103o are normal in the first week and do not require
cultures

84. Radioembolization or
Selective Internal Radiation Therapy
(SIRT)
This technique selectively targets a very high
radiation dose to all tumors (average dose of 280-
380 Gy) within the liver, regardless of their cell of
origin, number, size or location while at the same
time maintaining a low radiation dose to the normal
liver tissue (<40 Gy)

85. Radiation in HCC
• Traditional radiation therapy in management of unresectable HCC
demonstrated palliation of symptoms in >50% of patients and 20% signficant
tumor shrinkage
• Risk of radiation induced liver toxicity after uniform whole liver radiation to 30
Gy (<dose required to eradicate tumor) delivered over 3 weeks was 5%
Sakamoto I, et al. Complications associated with transcatheter embolization for hepatic tumors. Radiographics 1998;18:605-619
Gates J, et al. Chemoembolization of hepatic neoplasms: safety, complications and when to worry. Radiographics 1999;19:399-414.

86. Mechanism
• SIR-Sphere size is small enough to gain entry into tumor nodules but too large
to pass through the end capillary bed into the venous circulation
• Tumor vessels 25μm -75μm
• End arterioles 8 μm
• SIR-Spheres mean diameter 35 μm

87. Regulatory Status
• In US, regulated under the pre-market approval regulations (21 CFR Part 814)
• FDA approval March 2002
• Unresectable metastatic liver tumors from primary
colorectal cancer together with adjuvant intra-hepatic
chemotherapy with FUDR
• In Europe and UK, Europe and UK regulated under the Active
Implantable Medical Device Directive (90/385/EEC)
• CE Mark approval October 2002
• Primary and secondary (metastatic) liver cancer

88. Radio-embolization in HCC
• Partial response rate of 42.2% in phase 2 study of 108 patients
with unresectable HCC with/without portal vein thrombosis
• More study is needed
Kulick LM, et al. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma
with and without portal vein thrombosis. Hepatology. 2008;47:71-81

89. Patient Selection
Unresectable primary hepatic malignancy:
Hepatoma
Unresectable metastatic disease:
Colorectal
Breast
Pancreatic
Carcinoid
Neuroendocrine
Cholangio-carcinoma

90. Patient Selection
• Tumor board/ multidisciplinary team determination
that patient has unresectable liver tumor with a life
expectancy > 3 months
• ECOG 0,1,2
• Karnofsky score of 60% or higher

91. Patient Work-up
1) CT/MRI/PET imaging to confirm
• liver dominant disease + no CNS mets
• tumoral/nontumoral volume
• patent portal vein
2) Adequate synthetic and excretory liver function
• Total bilirubin < 2.0mg/dL
• Serum albumin > 3.0g/dL
3) Patient may be on systemic chemotherapy except Capecitabine,
Avastin, Erbitux
• Trials in progress to determine safety in conjunction with
Capecitabine, Avastin, Erbitux
4) No history of external beam radiation to the liver

92. Patient Work-up
• Two absolute contraindications
• reflux into arteries that supply the gastroduodenal region
• can result in gastritis, pancreatitis, gastric ulceration
• exaggerated hepatopulmonary shunting (lung shunt > 20%)
• can result in radiation pneumonitis
• To address these issues, a pre-treatment diagnostic hepatic angiogram
is performed

93. Gastroduodenal Artery
Right Gastric Artery
Hepatic Arteries
Ability to coil embolize
GDA and RGA and
others as necessary to
prevent reflux into
arteries in the
gastroduodenal region
Pre-treatment
hepatic arteriogram

94. After coil
embolization,
injection of 5-6
mCi of Tc-99m
labeled MAA as a
microsphere
surrogate into the
hepatic arterial
territory to assess
extent of
hepatopulmonary
shunting

95. Reduce implanted activity for lung shunting >
10%
Lung shunt fraction
Reduce implanted activity
by
0 – 10% No reduction required
11 – 15% Reduce by 20%
16 – 20% Reduce by 40%
> 20% Do not treat

96. Implanted activity calculation for a whole liver
treatment from the proper hepatic artery
• 1) Activity (GBq) = BSA*- 0.2 +
• 2) Reduce implanted activity for lung shunting as
described
• 3) Reduce implanted activity for special cases
• CRLMs – heavy pre-treatment with systemic chemotherapy
• HCC - cirrhosis
Tumor volume
Tumor volume + normal liver volume
*BSA = Body Surface Area

97. SIR-Spheres Meds
• Rocephin 1gm IV pre procedure. No home antibiotics.
• PPI or any H2 blocker one week before and for 4 weeks after.
• Medrol dose pack if not diabetic (script written at discharge).
• Ketorolac 10mg PO q 4-6 hours PRN pain x 5 days after
treatment.
• Ondansetron 8mg PO q 8 hours PRN N/V. or Promethazine
25mg tablets, one PO q 6hours PRN N/V.

98. Radiation Safety
• Exposure
• Bremsstrahlung is typically 15 uSv per Gbq at 15cm from the patient’s right side
(initially)
• Ward
• Outpatient procedure
• No pregnant women, children (‘three feet for three days’)
• Nursing from left hand side of patient
• Shielding unnecessary
• No special handling required for blood, body fluids, urine

99. Complications to be aware of…
• Postembolization syndrome – may occur in as many as 50%
pts; not as severe as that observed with TACE and is usually
dominated by fatigue and constitutional symptoms
• Gastrointestinal ulceration – incidence minimized with coil
embolization of right gastric, etc.
• Pancreatitis – incidence minimized with coil embolization of
gastro-duodenal artery

100. Complications to be aware of…
• Radiation pneumonitis – incidence practically zero with
routine work-up and Tc99 lung shunt study
• Radiation hepatitis (RILD) – increased risk in patients with
cirrhosis and reduced liver reserve
• Radiation Cholecystitis – clinically relevant radiation
cholecystitis requiring cholecystectomy is not common but
does occur

101. THANK YOU