Tumor Margins and the Accuracy

of Radiofrequency Ablation for

Treatment of Liver Metastases
Janice J. Kim
Dr. Bob Galloway
Vanderbilt University
Summer 2000

Outline

Motivation
Background
Problem and Proposed Solution
Methods and Results
Conclusions

Outline

Motivation
Background
Problem and Proposed Solution
Methods and Results
Conclusions

Motivation - Why Livers?

The liver is a common
site for metastatic
deposits
First filter of blood
from the bowel
Tissue factors

Metastatic tumors
outnumber primary
tumors 20:1

Sources of Metastases to the Liver

1. Colon
2. Lung
3. Pancreas
4. Breast
5. Gastric
6. Gallbladder
7. Prostate
8. Melanoma

Colorectal Cancer and the Liver

Approximately 150,000 Americans are
diagnosed annually with colorectal cancer
25% have liver metastases at presentation
An additional 50% will develop liver
metastases
There are over 50,000 deaths per year

Outline

Motivation
Background
Problem and Proposed Solution
Methods and Results
Conclusions

The Liver

Cleanses blood
Regulates metabolism
Manufactures proteins
Produces bile
Regulates hormones
Regulates cholesterol
Regulates essential
vitamins and minerals

Liver Physiology
Two major lobes
Blood inflow:
Hepatic portal vein
(75 percent)
Hepatic artery
(25 percent)

Blood outflow:
Hepatic veins to
inferior vena cava

Couinaud Segments
Eight functional segments
Left liver
Left lateral: II, III
Left medial: IV

Right liver
Right posterior: VI, VII
Right anterior: V, VIII

Caudate lobe: I

Hepatic Lobules

Structural unit
Roughly hexagonal
Central vein in center
Portal triads at
periphery
Bile duct
Hepatic artery
Hepatic portal vein

Metastatic Tumor Physiology

Size (diameter):
Small: 3 cm or less
Large: 5 cm or more

Shape
Consistency
Molecular expression:
Metalloproteinases
Adhesion molecules
Angiogenesis promoters

Metastatic Tumor Physiology

Change in blood supply
1 cm diameter
From portal vein to own blood supply derived
mainly from hepatic artery

Eventually outgrow blood supply

Necrotic center
Oxygen affects radiation sensitivity

Metastatic Liver Disease

Median survival measured in months

Six month survival: 10-35%
Majority of patients die within a year
Five year survival rate approaches zero

Diagnosis and Evaluation

Imaging techniques
Computed tomography (CT)
scan
Dynamic CT arterial
portography (CTAP)
Magnetic resonance imaging
(MRI)
Spiral CT
Ultrasound (US)
Intraoperative ultrasound
(IOUS)

Diagnosis and Evaluation

Blood tests
Laparoscopy
Immunoscintigraphy with monoclonal
antibodies

Current Treatments
Surgical resection
Chemotherapy
Systemic
Regional

Chemoembolization
Cryotherapy
Radiofrequency ablation

Hepatic Resection
Liver tissue is capable of
regeneration
Up to 75% of the liver can
be resected
Resection of segments
Can induce hypertrophy
of future liver remnant
Low mortality: < 5%
Low morbidity: <10%

Hepatic Resection Limitations

Conditions preclude resection
Diffuse liver involvement
Evidence of extrahepatic disease
Proximity to major vasculature

70-90% of cases do not indicate resection

5-year survival rate of 20-30%
Recurrence is common
Removal of healthy liver tissue

Hepatic Arterial Infusion

Access ports or implantable pumps
Rationale:
Selective delivery of high drug levels to liver
Hepatic artery is the primary blood supply of
liver metastases
High extraction of certain drugs in liver

Chemotherapy Limitations
Systemic:
20% response rate

Regional:

Benefits only small, select group

Liver toxicity and biliary sclerosis
Expensive
Morbidity rate

Chemotherapy Limitations
Complete eradication of tumor is rare
Tumor progression frequently resumes
when therapy is stopped
Little impact on long-term survival

Chemoembolization
Tumor drug concentrations 10-25 times
higher than infusion alone
Drugs remain in tumor for greater duration
Minimal systemic toxicity

Chemoembolization Complications
Post-embolization syndrome in 80-90% of
patients
Major complications (3-4%):

Hepatic insufficiency
Hepatic abscess
Tumor rupture
Cholecystitis
Nontarget embolization to the bowel

Cryotherapy
Destroys tissue with the freeze-thaw
process
Freezes at temperatures of -160 to -180F

Cryotherapy Limitations
20% 5-year survival rate for patients with
unresectable colorectal cancer
Size and proximity to major vascular
structures or bile ducts
Number of metastases

Cryotherapy Complications

Hypothermia
Coagulopathy
Myoglobinuria
Renal Failure
Cracking of the hepatic capsule
Elevation of liver enzymes

Radiofrequency (RF) Ablation

Cooks tumors with
heat generated from an
electrical current

How Does RF Ablation Work?

The probe heats the tissue
to above 100C
At >113F (60-65C),
protein is permanently
damaged and cell
membranes fuse)
Cells die within 15
minutes and over time are
gradually reabsorbed by
the body

Why RF Ablation?
Eliminates tumor with minimal damage to
healthy liver tissue
Can be done using minimally invasive
techniques
Light sedation
Small incision
Shorter hospital stay

RF Ablation
Complications and Limitations
Heat sink effect
Serious side effects: < 4%
Infection
Bile leakage
Breathing difficulties

Current maximum ablation zone: 5 cm

Outline

Motivation
Background
Problem and Proposed Solution
Methods and Results
Conclusions

Problem
Removal of a 1 cm safety margin along with the tumor
Loss of healthy liver tissue
Eliminates candidates for RF ablation, cryotherapy, and
hepatic resection
Error of RF probe from target point more likely to leave
tumor unablated

Research Focus
Is the 1 cm tumor margin really necessary?
How does the error of the RF probe tip from the
target point affect the amount of tumor ablated?

Outline

Motivation
Background
Problem and Proposed Solution
Methods and Results
Conclusions

Research Focus
Is the 1 cm tumor margin really
necessary?
How does the error of the RF probe tip
from the target point affect the amount
of tumor ablated?

Literature Review and Results

1986 British Journal of Surgery article by
Ekberg et al
Resection margin 10 mm
Maximum of 3 metastases
No extrahepatic disease

Literature Review and Results

Extent of resection margin vs. pathologically
positive/negative margins
0-10 mm margin vs. >10 mm
Narrow margins correlate strongly with extensive
disease
Microscopic bile duct, portal or hepatic vein
invasion, microsatellite lesions tend to be found
close to metastatic edge
Precludes risk of tumor rupture

Literature Review and Results

A 10 mm margin need not be strictly adhered

to for a curative hepatic resection as long as
the resection can be complete and a clear
margin is achieved

Research Focus
Is the 1 cm tumor margin really
necessary?
How does the error of the RF probe tip
from the target point affect the amount
of tumor ablated?

Goal
Matlab program
Calculate the amount of tumor left unablated as
a function of RF probe error
Plot the results

Calculating the Unablated Area

Calculating the Unablated Volume

Display tumor and ablation zone spheres
Calculate intersection volume between two
overlapping spheres
Display multiple data plots on the same
figure

Program Outline
Asks for tumor and ablation
zone diameters
Calculates and displays the
volumes
Plots the data
Asks user if he/she would
like to continue
Same tumor size
Different ablation zone
diameter

Calculating the Unablated Volume

Using the Program

Without explicitly including margins
Tumor size 3-7 cm
Ablation zone diameter 2-5 cm

With margins considered

Tumor size 3-7 cm (5-9 cm including margin)
Ablation zone diameter 2-5 cm

Results

Results

Results
Removal of larger tumors is beyond the
capabilities of a single RF ablation
Margin for error is severely limited by the
addition of the 1 cm margin

Outline

Motivation
Background
Problem and Proposed Solution
Methods and Results
Conclusions

Conclusion
The 1 cm tumor margin is not necessary as
long as the margins are clean
Using the Matlab ablation error program,
we now have an idea of how accurate RF
ablation needs to be under various
circumstances

Future Work
Modify the program to account for different
tumor shapes
Run ablation experiments
Test and modify the algorithm

Incorporate the information into the

development of ORION for interactive
image-guided hepatic surgery

Acknowledgements
Mad props to:

Dr. Bob
Mark Bray
Craig Duvall and the 2000 REU students
SNARL Lab
Center for Technology Guided Therapy
National Science Foundation