Review

Interstitial laser thermotherapy for liver tumours

M. Nikfarjam and C. Christophi
Department of Surgery, University of Melbourne, Austin Hospital, LTB 8, Studley Road, Heidelberg, Melbourne, Victoria 3084, Australia
Correspondence to: Professor C. Christophi (e-mail: c.christophi@unimelb.edu.au)

Background: Primary hepatocellular carcinoma (HCC) and metastases from colorectal cancer are the
most common malignant liver tumours. Surgical resection is the optimum treatment in suitable patients.
Interstitial laser thermotherapy (ILT) is gaining acceptance for the treatment of irresectable liver
tumours and as a potential alternative to surgery. An understanding of the principles of therapy and
review of clinical outcomes may allow better use of this technology.
Method: An electronic search using the Medline database was performed for studies on the treatment of
hepatic malignancy published between January 1983 and February 2003.
Results: Current information on the efficacy of ILT is based on prospective studies. ILT appears to be
a safe and minimally invasive technique that consistently achieves tumour destruction. The extent of
destruction depends on the fibre design, delivery system, tumour size and tumour biology. Real-time
magnetic resonance imaging provides the most accurate assessment of laser-induced tumour necrosis.
In selected patients with HCC and colorectal cancer liver metastases, ILT achieves complete tumour
necrosis, provides long-term local control, and improves survival, compared with the natural history of
the disease. In addition, ILT has survival benefits for patients with other tumour types, especially those
with isolated liver metastases from a breast cancer primary.
Conclusion: ILT improves overall survival in specific patients with liver tumours. Advances in laser
technology and refinements in technique, and a better understanding of the processes involved in laser-
induced tissue injury, may allow ILT to replace surgery as the procedure of choice in selected patients
with liver malignancies.

Paper accepted 19 May 2003

Published online in Wiley InterScience (www.bjs.co.uk). DOI: 10.1002/bjs.4326

Introduction and method availability, institutional experience and patient acceptance.

Surgical excision currently offers the best chance of
cure for both primary and secondary liver tumours, but
is applicable to only a small number of patients1 – 4 .
The major limiting factors include the anatomical
location of lesions and inadequate functional hepatic
reserve to allow complete tumour resection. Hepatic
resection is a procedure associated with appreciable
morbidity, particularly in patients with coexistent liver
disease1,4 – 9 . Interest has recently focused on interstitial
ablative techniques to increase the number of patients
who may benefit from tumour eradication and to
decrease the morbidity of therapy. Techniques include
focal hyperthermia, cryotherapy, chemical ablation and
electrolysis. These may be applied focally to destroy liver
tumours in a highly reproducible and minimally invasive
fashion. The local ablative therapy employed depends on its
Focal hyperthermia is the most widely used technique
and may be produced by interstitial laser thermotherapy
(ILT), radiofrequency ablation, percutaneous microwave
coagulation or high-intensity focused ultrasound. This
article reviews the status of ILT in the treatment of liver
tumours.
An electronic search using the Medline database was
performed for publications on the use of laser for the
treatment of hepatic malignancy from January 1983 to
February 2003. Selected articles with ‘laser’ and ‘liver’ in
the title, abstract or keyword list were reviewed.
General principles
The use of laser as a heat source to destroy liver tumours
was first reported by Bown in 198310 . Laser light can be
delivered precisely and predictably into most regions of

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1034 Laser treatment for liver tumours ž M. Nikfarjam and C. Christophi
the liver. Its effects depend on the physical properties of
the laser unit, delivery system design and the mechanisms
of laser-induced tissue injury.
Physical properties of lasers
Laser units have three basic components: a power source,
a lasing medium and reflecting mirrors. The light pro-
duced is of a specific wavelength and defines the prop-
erties of the laser system and the extent of tissue pen-
etration. An infrared light wavelength of between 800
and 1100 nm is the optical window for achieving max-
imal tissue penetration and homogeneous spread11,12 .
Neodymium : yttrium–aluminium–garnet (Nd : YAG)
(wavelength 1064 nm) and diode (wavelength 800–
980 nm) lasers are used for ILT. The Nd : YAG laser
has the higher tissue penetration and produces the greater
volume of tissue destruction. It is the preferred laser unit
for ILT, despite being larger and less portable than diode
devices.
Fibre design
The extent of tissue necrosis is predominately determined
by the laser power that can be applied before tissue
charring occurs. This is mainly governed by the fibre
design13 – 19 . Increasing power enhances light transmission,
but results in progressive temperature increase around the
fibre tip, which eventually leads to tissue charring and
carbonization. Charred tissue limits light penetration and
tissue necrosis20 – 23 . Each fibre type works best within a
particular power range. The most common fibre types used
are the bare-tip and cylindrical diffusing quartz fibres.
Traditional bare-tip fibres are 400–600 µm in diameter,
have a light-emitting tip and are introduced into tumours
using fine-bore (21–23 G) cannulas. Typical power
settings vary between 2 and 4 W24 – 27 . The maximum
achievable lesion diameter with bare-tip fibres is 2 cm28,29 .
Beam-splitting capabilities allow power delivery into
multiple bare fibres for simultaneous treatment of large
tumours16,19 . Multifibre systems have a synergistic effect
owing to reduced heat dissipation between fibres. This
increases the volume of tissue necrosis by fourfold to
sixfold, while reducing application times18,19,30 . Four-
fibre systems produce a maximal lesion diameter of
approximately 5 cm18 .
Modern quartz diffusing laser fibres have cylindrical
applicators that are 1–2 mm in cross-sectional diam-
eter and function more efficiently at higher power
settings than bare fibres. Light is emitted over the
entire diffusing surface31 , usually at power settings of
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between 4 and 10 W32 – 34 . Minimal intralesion variability
and minimal charring contribute to large volumes of
necrosis14,15,17,23,35,36 . These fibres require larger can-
nulas (13–15 G) for percutaneous insertion than bare-tip
fibres and produce a lesion size that approaches 5 cm at
appropriate power settings33,34 .
Water-cooled laser systems decrease temperature gra-
dients around the fibre tip to minimize tissue charring
and maximize tissue necrosis. These systems incorporate
either bare or diffusing fibres that operate more efficiently
at higher power settings than other delivery systems37 – 43 .
Modern cooled fibre systems have a built-in recirculating
chamber that surrounds the main laser light source44 . This
prevents direct coolant contact with the tissue, which can
cause an increase in interstitial pressure and increase the
risk of tumour seeding. These fibres have large cross-
sectional probe diameters (3 mm) that necessitate use
of wide-bore cannulas (9–11 G) for percutaneous local-
ization. They can achieve tissue necrosis of 4–6 cm in
maximum diameter at power settings of 25–30 W42 – 45 .
Mechanism of laser-induced injury
The extent of tissue injury depends not only on the
laser source and fibre type, but also on interaction of
the laser with the tissue. Tissue destruction depends on a
balance of thermal effects, changes in vascular permeability
and complex processes involving the stimulation of
inflammatory mediators and the immune response.
The biological effects of the laser light are based on laser
photon energy transformation to heat following absorption
by tissue-specific chromophores46 . The temperature and
exposure time determine the heat-induced cellular effects.
Classical hyperthermia relies on temperatures of 42–45◦ C
for periods of 30–60 min28,47 – 49 . The inactivation of
vital enzymes is a key feature of tissue injury at these
temperatures37 . There is an exponential decrease in the
exposure time needed for irreversible cellular damage as
the temperature approaches 60◦ C. Protein denaturation,
tissue coagulation and immediate cell death occur at
temperatures of 60–140◦ C15 . Superimposed on this
process is vaporization that results from evaporation of
tissue water between 100 and 300◦ C. Tissue carbonization,
charring and smoke generation occur at 300–1000◦ C50 .
Once carbonization occurs at the laser fibre tip, the process
amplifies owing to further increases in temperature, with
the fibre acting as a point heat source, to achieve its effects
by heat diffusion rather than light penetration51 .
Tissue perfusion is the key variable determining the
tissue temperature profile and the degree of necrosis52 .
Tissue damage adjacent to large intrahepatic vessels is
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 M. Nikfarjam and C. Christophi
less pronounced than at other sites because of the heat-
sink effect29,53 . High blood flow in large vessels dissipates
heat, and protects adjacent tissue and vascular endothelium
from thermal injury. Laser light is absorbed by haem
in erythrocytes and is transferred away from the region
of laser application51 . The effect of blood flow on heat
dissipation is more noticeable in the normal liver than in
tumour tissue, owing to the presence of larger vessels and a
greater ability to augment blood flow by vasodilatation30,54 .
Treatment failures following ILT usually occur at the
tumour periphery, in the region of highest tumour blood
flow55,56 . Blood flow occlusion can significantly increase
the area of tissue destruction by reducing heat dissipation55 .
The application of ILT also leads to a series of cellular
and molecular events that result in progressive tissue
destruction after the cessation of the initial stimulus;
the mechanism is not yet defined28,29,57 . Heat-induced
expression of cancer antigens and subsequent antitumour
response may be one important mechanism of progressive
tissue destruction58 – 60 .
Clinical principles
Patient selection
Present indications for ILT include irresectable disease
owing to the anatomical location of tumours or poor
functional hepatic reserve, patient preference and medical
Colorectal liver metastases
Staging
Triphasic CT of the liver
CT of the abdomen, pelvis, chest
Whole-body PET
Localized to
the liver
Resectable
Irresectable
≤ 5 metastases
Laparoscopy ≤ 5 cm diameter
Laparotomy
Interstitial
Intraoperative US laser
thermotherapy
Resection
Protocol for management of patients with colorectal liver metastases. CT, computed tomography; PET, positron emission
Fig. 1
tomography; US, ultrasonography
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ž Laser treatment for liver tumours 1035
contraindications to surgery41,61 . In patients with colorec-
tal cancer liver metastases, the authors’ current institutional
protocol is initially to perform extensive non-invasive
radiological imaging to exclude extrahepatic disease. This
includes contrast-enhanced computed tomography (CT) of
the chest, abdomen, pelvis and whole-body positron emis-
sion tomography. Patients with irresectable liver metastases
and no evidence of extrahepatic disease are treated by ILT if
no more than five lesions are present and no lesion exceeds
5 cm in maximum diameter (Fig. 1). Similar protocols are
used in other institutions25,41 .
ILT treatment of irresectable lesions may extend the
indications for surgery in certain situations by downstaging
tumours to allow resection. In other situations, ILT may
be used in combination with surgical resection to achieve
complete tumour clearance1 . Patients with extrahepatic
disease are usually excluded because of their overall poor
prognosis24,41,42,62 , although ILT may provide significant
palliation for those with symptomatic liver involvement
that is not responsive to other treatment modalities.
Treatment techniques
ILT delivered percutaneously is the preferred option in
most cases26,63 – 65 . When percutaneous localization is not
possible, options include open and laparoscopically guided
techniques. Apart from enabling accurate tumour local-
ization, open and laparoscopic methods allow detection
Extrahepatic
metastases
Irresectable
> 5 metastases
> 5 cm diameter
Selective internal Systemic
radiation chemotherapy
and
systemic
chemotherapy
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1036 Laser treatment for liver tumours ž M. Nikfarjam and C. Christophi
of previously unrecognized disease, especially when com-
bined with intraoperative ultrasonography66 – 68 . They also
allow portal clamping to maximize ILT-induced tumour
necrosis69,70 .
In the authors’ institution ILT is performed under intra-
venous sedation and local anaesthesia, with prophylactic
antibiotic cover. Tumours are localized under ultrasono-
graphic control using needles of an appropriate size for
the fibre type. Laser power is administered to produce
complete tumour necrosis. The extent of necrosis is mon-
itored by real-time ultrasonography. Most patients are
treated on a day-case basis and can resume normal activ-
ities within 12–24 h of therapy. The total number of
treatments varies with the size and number of lesions, and
the results of follow-up investigations. Contrast-enhanced
CT is performed 6 weeks after treatment and at intervals
of 3–6 months thereafter.
Imaging for interstitial laser thermotherapy
Imaging has a dual role. It allows monitoring of necrosis
at the time of treatment and the detection of residual
or recurrent disease after therapy. Real-time monitoring
that accurately correlates with the final volume of
tissue necrosis is essential for consistent and complete
tumour destruction71 . A variety of modalities are used,
including ultrasonography, magnetic resonance imaging
(MRI) and CT.
Ultrasonography
Ultrasonography is widely used for real-time monitoring
because of its availability, simplicity and cost-effectiveness.
It detects tissue changes due to coagulative necrosis
that expand spherically from the fibre tip. Heated
tissues become hyperechoic with water loss, which is
most pronounced when there is tissue charring72 – 75 .
Ultrasonographic changes are less obvious with fibre
systems that minimize charring76 . Imaging artefacts are
common and may cause problems in distinguishing
reversible from irreversible damage77 – 79 . Several animal
studies have demonstrated that changes seen immediately
on ultrasonography often overestimate the histological
area of necrosis73,74,76,80 . Delayed images taken 2–5 h
after laser thermotherapy correlate more closely with
histological findings76,80 .
The use of ultrasonography in follow-up is generally
limited81 . Still, recent developments in colour Doppler
ultrasonography and microbubble contrast delivery have
improved its ability to assess tissue perfusion and
detect residual disease. The sensitivity of Doppler
ultrasonography is greatest when performed immediately
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before and after local ablative techniques, particularly for
hypervascular tumours82,83 .
Computed tomography
The main role of CT is in the detection of residual
or recurrent tumours following ILT. Real-time CT
is inaccurate in detecting the early signs of laser-
induced tissue injury. However, contrast-enhanced CT
performed 24 h after ILT identifies tissue necrosis as
non-perfused areas, and correlates closely with histological
findings84 . Residual disease appears as a region of contrast
enhancement adjacent to non-perfused tissue. The margins
of necrotic tissue become indiscrete within a few days
of therapy because of inflammatory changes84 . Once
inflammatory changes resolve a few weeks later, early
local recurrence is clearly identified as a contrast-enhanced
region adjacent to an area of necrosis.
Magnetic resonance imaging
Real-time MRI is the most accurate method of assessing
laser-induced necrosis43,85,86 . Its use is currently limited
by high operational costs and a lack of availability. Tumour
localization is usually performed by ultrasonography, and
MRI is simply used for treatment monitoring. Open-plane
MRI units are becoming more widely available, allowing
tumour localization, fibre manipulation and monitoring to
take place in a single setting.
MRI has the highest correlation with histology in both
animal and human studies. It guides treatment sessions,
and allows optimization of laser power and duration to
ensure adequate temperature increases beyond the tumour
margins to achieve complete tumour necrosis43,85 – 89 . MRI
signals detect hydrogen ion fluctuations that result from
thermal changes. It detects temperature changes of less
than 1◦ C with a spatial resolution of 2 mm90 . It is
particularly accurate when tissue temperatures are between
37 and 50◦ C40 . At temperatures beyond 50◦ C, severe
metabolic, physiological and structural damage occurs, and
tissue signal properties are altered reducing the accuracy of
temperature correlations91 . Fast low-angle shot MRI and
T-weighted studies are currently the favoured techniques
to determine the extent of necrosis89 .
MRI is also well suited to detecting residual and
recurrent tumours. Gadolinium-enhanced MRI detects
residual tumours in the transition zone between thermally
damaged and undamaged tissue when performed 24 h after
therapy. Recurrent disease is best detected at least 2 weeks
after the completion of ILT, when minor enhancement
due to proliferation of mesenchymal cells, fibroblasts and
bile duct epithelium has resolved sufficiently92 .
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 M. Nikfarjam and C. Christophi
Clinical outcomes
Successful treatment of patients with hepatocellular
carcinoma (HCC), colorectal cancer metastases and other
liver metastases has been reported in recent prospective
studies. Assessment of treatment outcome is based on
several factors, including long-term survival, complete
tumour destruction, tumour recurrence and complications.
There are currently no randomized clinical trials that
compare ILT with other therapies. Treatment is therefore
compared with the natural history of untreated disease
and with the results of surgery to determine any
potential benefits. Clinical studies with a minimum of
ten patients and/or months of follow-up are summarized
in Table 124 – 27,32,33,41 – 43,61,62,93 – 96 . The clinical outcomes
of patients with HCC, colorectal cancer metastases and
other tumour types are discussed separately.
Hepatocellular carcinoma
Patients with untreated HCC have a median survival
ranging from 3 to 6 months97 . The resection rate for
HCC varies between 10 and 37 per cent98 – 100 , which
confers a 5-year survival rate of about 50 per cent101 .
Despite resection, recurrences occur in up to 80 per cent
of patients, largely reflecting the multicentric nature of
hepatocarcinogenesis97,102 – 105 . Fewer than 10 per cent of
these patients are suitable for repeat resection104,105 . Local
ablation is particularly suited to HCC, especially when poor
functional hepatic reserve precludes resection or when liver
transplantation is not an option.
Several reports have assessed long-term survival after
ILT treatment of HCC24,93 – 95 . Pacella et al.94 treated 74
patients (92 lesions) with biopsy-proven HCC using bare
fibres with a beam-splitting device. All were either poor
surgical candidates or had irresectable disease. Patients
older than 80 years, those with evidence of extrahepatic
disease and those with Child–Pugh class C cirrhosis were
excluded. Most had single tumours with a mean diameter
of 2·4 cm and required a median of two treatment sessions,
during a mean follow-up of 25·3 months. Complete
response to therapy was observed in 97 per cent of tumours
at 3 months. Only three tumours failed to show a complete
response, and this was attributed to inaccurate tumour
localization. The 3- and 5-year survival rates for all patients
were 68 and 15 per cent respectively. Fifty-eight patients
in this series had Child–Pugh class A cirrhosis, and had 3-
and 5-year survival rates of 73 and 31 per cent respectively.
Sixteen patients with Child–Pugh class B cirrhosis had
3- and 5-year survival rates of 68 per cent and zero
respectively. The rate of local recurrence at the tumour
treatment site was 1·6 per cent at 1 year and 6 per cent at
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ž Laser treatment for liver tumours 1037
5-year follow-up. Overall hepatic recurrence was 24 and
73 per cent at 1 and 5 years respectively.
In a further study, Pacella et al.95 used ILT with
doxorubicin hydrochloride-based transcatheter arterial
chemoembolization (TACE) to treat 30 patients with
‘large’ HCCs greater than 3 cm in diameter (mean 5·2 cm).
These patients were either poor surgical candidates or
had irresectable disease. Mean follow-up was 17·1 months.
Nineteen patients had solitary lesions. The remaining 11
also had one to three ‘small’ tumours (less than 3 cm).
ILT was performed over 4 weeks to achieve a minimum
reduction in tumour size of 15 per cent before TACE.
Patients had a mean of 4·2 ILT treatment sessions
(range 1–14) and CT was used to monitor response
to therapy. Less than half of the ‘large’ tumours were
avascular at the end of the 4-week assessment period.
Segmental TACE was performed using digital angiography
30–90 days after the initiation of ILT treatment. CT
assessment 15–20 days after the completion of TACE
showed 90 per cent complete necrosis of ‘large’ tumours.
The cumulative survival rate at 3 years was 40 per cent
with a local recurrence rate of 7 per cent.
A high response rate to therapy is reported in other
studies when tumour size does not exceed 4 cm24,93 .
Giorgio et al.24 achieved an 82 per cent complete response
in 77 patients with a total of 85 biopsy-proven HCCs of
mean diameter 3·2 cm. The response rate of small HCCs to
ILT is similar those of other thermal ablative therapies106 .
Most ILT series also include patients with HCCs close to
the hepatic hilum and confluence of the hepatic veins
that are difficult to ablate. These patients are rarely
treated by other thermal ablative techniques75,94,95,107 .
The local recurrence rate is generally less than 10 per cent
for HCC treated by ILT; this is similar to the rate for
other techniques94,95,108 – 112 . The incidence of tumour
recurrence away from the site of treatment is similar for all
local ablative techniques and reflects the natural history of
hepatocarcinogenesis106,113 .
Colorectal liver metastases
The median survival of untreated patients with liver
metastases from colorectal cancer varies between 6 and
12 months. The 5-year survival rate is approximately
1 per cent114 – 117 ; median survival ranges from 21
to 24 months in those with single metastases, from
10 to 18 months for those with multiple unilobar
metastases and from 2·5 to 3 months in patients with
bilobar disease117 – 119 . When systemic chemotherapy with
5-fluorouracil or fluorodeoxyuridine and folinic acid is
administered, median survival improves only marginally1 .
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 Table 1 Interstitial laser thermotherapy for malignant tumours

Follow-up
Patient Tumour method and
Reference characteristics Indications* characteristics† Technique Complications* tumour control Survival*

41 705 patients Previous surgery 36% ≤ 5 cm Water-cooled PC Death from bowel injury (1) CT assessment Overall Mean 4 years;

Published by John Wiley & Sons Ltd

393 CRC, 127 breast, Bilobar disease 35% ≤ 5 total (mean 2·8) diffusing fibre Pleural effusion 7·3% (6 months) 5 years 36%
185 others Irresectable 22% MRI and US Intrahepatic abscess 0·4% Overall 97·9% local CRC: Mean
(1981 lesions) Refused surgery 7% Subcapsular haematoma control 41·8 months; 5 years
3·1% 30%
Breast: Mean 4·3 years;
5 years 34%

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62 80 patients Irresectable ≤ 10 cm (median 5 cm) Diffusing fibre Pneumothorax (3) CT assessment Median 24·6 months;
80 CRC ≤ 5 total (median 2) PC bare fibre Bradycardia (5) (6 months) 5 years 3·8%
(162 lesions) US Jaundice (2) 67% local control
Fistula (1)
Pyrexia (2)
93 8 patients Unfit or irresectable ≤ 7 cm PC bare fibre Abdominal wall bruising (1) CT (1–3 months) Median 9 (range
8 HCC ≤ 4 total US Fever (1) Complete response in 3–18) months
(18 biopsy-proven Bradycardia (1) tumours less than
1038 Laser treatment for liver tumours ž M. Nikfarjam and C. Christophi

lesions) 4 cm
94 74 patients Unfit or irresectable ≤ 4 cm (mean 2·4 cm) PC bare fibre Mild pain (61) CT (3 months) Overall: 3 years 68%;
74 HCC ≤ 3 total Beam splitter Pleural effusion (19) 97% complete 5 years 15%
(92 biopsy-proven US Subcapsular haematoma (1) response Child A (58): 3 years
lesions) 73%; 5 years 31%

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Child B (16): 3 years
68%; 5 years 0%
95 30 patients Unfit, irresectable or 30 large tumours PC bare fibre Severe pain (1) CT (45–110 days after Overall: 1 year 92%;
30 HCC previous transplant ≤ 10 cm (mean 5·2 cm) Beam splitter Mild pain (11) laser) 3 years 40%
(45 biopsy-proven 15 small tumours TACE Pleural effusion (10) Large tumours 90%
lesions) ≤ 3 cm (mean 1·9 cm) US complete response
≤ 4 total Small tumours 100%
complete response
42 20 patients Irresectable or patient < 4 cm (mean volume Water-cooled PC Mild pain (16) MRI (3 months) Follow-up 3–14 months
16 CRC, 4 others refusal 21·6 cm3 ) diffusing fibre 100% complete Survival NA
(34 lesions) ≤ 5 total (mean 1·7) US response (18
HAE patients)
61 69 patients Irresectable, unfit, ≤ 8 cm (mean 3·9 cm) PC bare fibre Death from hepatic NA Overall Median
69 CRC extrahepatic ≤ 16 total (mean 2·9) Beam splitter infarction (1) 27 months; 4 years
(200 lesions) disease (20) US Needle-track seeding (2) 22%
Abscess (2) Subgroup (24) < 5 cm
≤ 3 lesions: median
33 months

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 24 104 patients Irresectable, elderly, HCC ≤ 7 cm (mean PC bare fibre Liver failure (3) CT (day 7) Follow-up: HCC mean
77 HCC, 25 CRC, refused for surgery 3·2 cm) Beam splitter Ileus (2) HCC 82% complete 4·5 months;
2 lung or unfit Others ≤ 9 cm (mean US response metastases mean
(116 biopsy-proven 4·2 cm) Metastases 77% 4·8 months
lesions) ≤ 3 total complete response Survival NA
43 12 patients Unsuitable for surgery ≤ 8 cm Water-cooled PC Pain (3) MRI (4 and 10 weeks) Median 6 (range 0–36)
8 HCC, 2 CRC, ≤ 6 total diffusing fibre Pyrexia (1) Complete response in weeks
2 others MRI Vasovagal response (1) 2 of 8 patients
(27 lesions) reviewed

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96 8 patients Irresectable ≤ 12 cm Laparotomy Death from multiorgan CT (6 months) Median 8·3 months
5 CRC, 1 pancreatic, ≤ 7 total (mean 3) Sapphire tip fibre failure (1) 16% complete
2 HCC US Pleural effusion (2) response
(23 lesions)
27 26 patients Mostly irresectable Size NA PC or laparotomy Transient pyrexia CT (6 months) NA
23 CRC, 3 HCC ≤ 6 total (mean 2·5) Bare fibre 68% complete

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(65 lesions) US response
26 10 patients Irresectable or patient Metastases ≤ 7 cm Laparotomy Fever (2) CT (6 months) NA
6 CRC, 2 breast, request (mean 2·5 cm) Bare fibre Vasovagal response (2) 8% complete
2 HCC ≤ 3 total (mean 1·7) Biliary collection (1) response
(17 lesions)
25 21 patients Irresectable, unfit or ≤ 15 cm (mean 3·2 cm) PC bare fibre Small pleural effusion (6) CT (6 months) Median survival
15 CRC, 6 others refused surgery ≤ 10 total (mean 3·1) US Pain (11) 38% complete 7·5 months
(55 lesions treated) Pyrexia (NA) response
33 11 patients Bilobar disease or ≤ 4 cm (mean 2·6 cm) PC or laparotomy Mild pain (3) US and biopsy NA
11 CRC extrahepatic cancer ≤ 3 total (mean 1·5) Diffusing tip Fever (2) (6 months)
(16 lesions) (8) Thermocouple Pleural effusion (1) 75% complete
response
32 5 patients Unfit (4) or refused (1) ≤ 5 cm (mean 2·4 cm) Diffusing tip Mild pain (1) CT (6 months) NA

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5 HCC ≤ 3 total Laparotomy 40% complete
(7 lesions) Thermocouple response

*Values in parentheses are actual numbers of patients. †Total refers to number of lesions. CRC, colorectal cancer; HCC, hepatocellular carcinoma; CT, computed tomography; MRI, magnetic
M. Nikfarjam and C. Christophi

resonance imaging; US, ultrasonography; TACE, transcatheter arterial chemoembolization; HAE, hepatic artery embolization; PC, percutaneous; NA, not assessable.
ž Laser treatment for liver tumours

British Journal of Surgery 2003; 90: 1033–1047

1039
1040 Laser treatment for liver tumours ž M. Nikfarjam and C. Christophi
Surgical resection offers the best chance of a cure, even
though it is applicable to only 10–25 per cent of patients
with liver metastases1 – 4 . The 5-year survival rate after
resection varies between 20 and 51 per cent120 . The overall
recurrence rate ranges from 40 to 80 per cent, including
both local and distant disease4,6,121 – 128 . Only 10–15
per cent of patients with recurrent disease are suitable
for repeat resection, with similar long-term survival to that
after the initial primary resection129,130 .
Many small series report the success of ILT in radically
ablating colorectal cancer liver metastases26,33,42,131,132 .
More recently, large series have shown that ILT improves
the outlook compared with the natural history of the
disease. Mack et al.41 reported a 5-year survival rate of
30 per cent for 393 patients with colorectal cancer liver
metastases treated by ILT. The mean survival in this
series was 41·8 months and this is similar to the results
of surgical resection. Patients had either recurrent disease
following previous surgery (36 per cent), bilateral tumours
(35 per cent), irresectable disease (22 per cent) or refused
surgery (7 per cent). Patients with extrahepatic disease,
tumours greater than 5 cm or those with more than five
lesions were excluded from this study. Those with one
or two colorectal cancer metastases had a longer survival
than those with three or more lesions, with a mean of
50·4 and 38·4 months respectively. The ability to achieve
complete tumour destruction in a single session improved
with the experience of the authors. Overall, 705 patients
with various liver tumours were treated using water-cooled
fibres with real-time MRI monitoring. Local tumour recur-
rence at 3 months in an initial group of 130 patients was
22·2 per cent, requiring further treatment. This decreased
to 0·8 per cent at 3 months for the last 575 patients in
the series. The control rate of tumours at 6 months was
97·9 per cent. To improve local tumour control further,
Wacker et al.42 used hepatic artery embolization during
percutaneous ILT to reduce heat dissipation. This series
consisted of 20 patients (16 with colorectal cancer), with
tumours no greater than 4 cm in diameter (mean vol-
ume 21·6 cm3 ). MRI at 3 months’ follow-up showed no
evidence of residual disease (none of 18).
In a series of 69 patients with colorectal cancer liver
metastases treated by ILT, Gillams and Lees61 reported
a 4-year survival rate of 22 per cent. This series included
20 patients with extrahepatic disease. The mean tumour
diameter treated was 3·9 cm. The overall median survival
was 27 months and this was significantly greater than
that of a similar group of patients treated by systemic
chemotherapy. In a subgroup of 24 patients with fewer
than four tumours and lesions not exceeding 5 cm,
median survival increased to 33 months. Christophi et al.62
Copyright  2003 British Journal of Surgery Society Ltd
Published by John Wiley & Sons Ltd
treated 80 patients with irresectable colorectal cancer
liver metastases with a maximum diameter of 10 cm
(median 5 cm). Patients with more than five lesions or
extrahepatic disease were excluded from the study. The
overall median disease-free survival was 24·6 months and
the 5-year survival rate was 3·8 per cent. Differences in
outcomes between series may reflect differences in patient
selection, tumour characteristics, monitoring and laser
delivery. There appears to be a survival advantage with
ILT treatment compared with the natural history of the
disease in all large recent series; this approaches the results
of surgical resection in certain situations.
ILT series often include patients with recurrent
tumours following surgical resection41,61 . Repeat hepa-
tectomy is potentially curative and allows accurate disease
restaging41,133,134 . It is, however, technically more difficult
than a first hepatectomy, with an associated mortality
rate of 2–5 per cent and a morbidity rate of 25–30
per cent133,134 . Shankar et al.135 reported 19 patients
treated by ILT for recurrent disease after hepatectomy
who were unsuitable for surgery. No major complications
were observed and the median survival of 16 months was
similar to the results of surgery133,134,136 – 138 . Christophi
et al. treated 14 patients with irresectable recurrent tumour
by ILT, after primary hepatic resection. Median sur-
vival was 36·3 months, with a 5-year survival rate of 17·2
per cent (C. Christophi, M. Nikfarjam, V. Muralidharan
and C. Malcontenti-Wilson; unpublished data). Some
studies of radiofrequency ablation for recurrent disease
have shown similar results139 .
Other tumours
Breast cancer is the commonest cancer in women in West-
ern society. Over half the patients with metastatic breast
cancer have liver metastases, but isolated liver involvement
occurs in no more than 5 per cent of instances140 . Median
survival for those with liver metastases without surgical
resection ranges from 1 to 15 months, even with standard
chemotherapy141 – 143 . The 5-year survival rate after liver
resection ranges from 9 to 25 per cent, with a median
survival time of 15–41 months144,145 . Reported series are
small and contain a heterogeneous group of patients. More
than half of the patients considered for resection are discov-
ered to have diffuse liver lesions or peritoneal dissemination
at the time of laparotomy144 . Mack et al.41 reported 127
patients with breast cancer and isolated liver secondaries
treated by ILT. Mean survival exceeded 50 months and
the 5-year survival rate was 34 per cent. These results are
similar to those of surgical resection144,145 .
Occasionally patients with other metastatic tumours
derive benefit from liver-directed therapies. Ablative
www.bjs.co.uk British Journal of Surgery 2003; 90: 1033–1047
 M. Nikfarjam and C. Christophi
techniques appear to be particularly suited to those with
functional neuroendocrine liver metastases, for which
potentially curative surgical resection is possible in only
about 10 per cent146 . When complete tumour clearance
cannot be achieved, local ablation may decrease tumour size
and hormone production to provide significant symptom
relief147 . There are also a few reports of a favourable
response to ILT treatment for tumours from other
primary sites including stomach, pancreas, kidney and
lung25,34,43 .
Complications
The operative mortality rate associated with surgical
resection of liver tumours is currently about 1 per cent,
but the morbidity rate ranges from 16 to 22 per cent4 – 9 .
In comparison, deaths related to ILT are rare. There are
isolated reports of death from gas emboli132 , multisystem
organ failure96 , massive hepatic infarction148 and small
bowel perforation34 , mostly occurring during the learning
phase of treatment by ILT.
Clinically relevant side-effects are uncommon. Minor
discomfort at the fibre insertion site is widely reported
and can be controlled with appropriate analgesics. A
temperature rise over 38◦ C occurs in up to one-
third of patients and rarely lasts beyond 24–48 h44 .
Temperature increases relate to mild sterile peritonitis or
to the release of inflammatory mediators from necrotic
tumours69 . The most common clinically significant
complications of ILT are pleural effusions and liver
abscesses. Mack et al.41 summarized his institutions
experience of treating 705 patients with 1981 liver lesion,
undergoing 7148 laser applications. They noted pleural
effusion and intrahepatic abscess in 7·3 and 0·4 per cent
of patients respectively. Other complications included
subcapsular haematoma (3·1 per cent), pleural empyema
(0·1 per cent), intrahepatic bleeding (0·2 per cent), intra-
abdominal bleeding (0·2 per cent), local infection at the
puncture site (0·2 per cent) and bile duct injury (0·1
per cent)34,41,44,149,150 . Clinically relevant complications
occurred in less than 2 per cent of patients. All
intrahepatic abscesses and pleural empyemas required
drainage. Pleural effusions needed drainage in less than
20 per cent of instances and only if the volume exceeded
1000 ml.
The adverse consequences of tumour seeding after
percutaneous biopsy are well recognized; 20 per cent of
patients have developed seeding along the biopsy track in
some series151 – 154 . There are only two reports of tumour
seeding following ILT, making this an extremely rare
complication of this procedure24 .
Copyright  2003 British Journal of Surgery Society Ltd
Published by John Wiley & Sons Ltd
ž Laser treatment for liver tumours 1041
Limitations and future directions
Local tumour recurrence continues to be a problem after
ILT treatment of larger tumours. Treatment limitations
are most notable when the size of the lesion exceeds
5 cm. Although multiple-fibre systems can address this
problem, single-fibre application is preferred if ILT is
to be considered a truly minimally invasive procedure.
Continued equipment and fibre modifications are likely
to produce larger lesions with a single fibre. Less
invasive means of blood flow occlusion using laparoscopy,
selective tumour embolization, temporary angiographic
portal balloon occlusion and, more recently, antivascular
agents may maximize tumour destruction in specific
cases96,155 – 160 . Complete tumour destruction may also be
improved by a greater availability of MRI for efficient real-
time monitoring. A better understanding of the processes
involved in laser-induced tissue injury, including the effect
of therapy on hepatic and extrahepatic micrometastases,
may also identify methods of reducing overall recurrence.
Conclusions
Most patients with primary and secondary liver malignancy
have a poor prognosis. A small number, however, are
amenable to surgical resection and have long-term survival.
Operation is currently the only well proven way of
achieving complete tumour removal and appreciably
improving survival. If surgery is not possible, ILT is
a minimally invasive, palliative, and potentially curative
option. In selected patients with HCC, colorectal cancer
liver metastases and other types of liver malignancy, it can
improve survival to a degree similar to that of surgical
resection. ILT allows a greater proportion of patients
with liver malignancy to be treated than surgery alone,
but a sound knowledge of the principles of treatment
is essential to maximize the use of this technology. The
extent of tissue necrosis is variable and depends on the laser
device, fibre type used, power settings, exposure times and
tumour biology. Necrosis may be incomplete, particularly
in tumours that exceed 5 cm in diameter. Continued
refinements in laser technology, a better understanding
of the mechanisms involved in laser-induced tissue injury,
and innovative methods of manipulating these mechanisms
may allow ILT to replace surgery as the primary treatment
for liver malignancy in selected patients.
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