Introduction
Colorectal cancer is a malignancy with high
incidence. The main cause of mortality is metastases, and the liver
is the most common target organ in colorectal cancer (1). In total, 20–25% of colorectal cancer
patients are diagnosed with liver metastases, and another 20–25%
with metachronous hepatic metastases. The main method used to treat
colorectal liver metastases (CRLM) is hepatectomy, however, only
10–20% patients are suitable for this procedure (2). Image-guided thermal ablation has been
developed and is now widely used to treat liver tumors.
Additionally, radiofrequency ablation (RFA) is a safe,
well-tolerated, repeatable and less invasive approach to treat CRLM
(3,4). Whilst, microwave ablation (MWA) is
highly valued, as it has a wide ablation diameter, high ablation
rates, low heat sink effect and short duration (5,6), the
available studies of MWA on CRLM are fewer in number than those of
RFA. The present study aimed to assess the feasibility, safety and
efficiency of ultrasound-guided percutaneous microwave ablation
(MWA) on liver metastases from colon or rectal cancer.
Materials and methods
Patients
All patients enrolled in the present study were
treated for CRLM using ultrasound-guided percutaneous MWA between
June 2009 and May 2012 in the Department of Interventional
Ultrasound, in the Chinese People’s Liberation Army General
Hospital (Beijing, China). The study was approved by the ethics
committee of Chinese PLA General Hospital (Beijing, China).
Inclusion criteria
To be eligible for MWA, the following inclusion
criteria were used: Tumor diameters of <5 cm for single liver
tumors; tumor diameters of <3 cm for 2–3 tumors; no invasion of
the blood vessels, bile duct and adjacent organs; no distant
metastasis; and normal coagulation.
Treatment
All necessary examinations were performed prior to
the treatment, and signed informed consent was obtained from each
patient. Liver lesions were clearly displayed upon two-dimensional
ultrasound, and if the image was not clear, it was located by
contrast-enhanced ultrasound. All the patients were treated with
intravenous anesthesia, a cooled-shaft microwave system (KY-2000;
Kangyou Medical, Nanjing, Jiangsu, China), two coaxial cables and
two water-pumping machines, which could simultaneously drive two
15-gauge polytetrafluorethylene-coated cooled-shaft antennae. The
generators were able to produce 1–100 W of power at 2,450 MHz.
Three types of antennae, with 0.5, 0.7 and 1.1 cm tips, were chosen
according to the size of the tumor, diameter <2, 2–3 and >3
cm, respectively. A thermal monitoring system with 21-gauge
thermocouple needles was equipped in the MWA machine. These needles
function by monitoring the real-time temperature percutaneously at
a specified location (7,8).
Follow-up visits
Subsequent to 3 days of treatment, all patients were
examined by contrast-enhanced ultrasound to determine the
inactivated condition of the tumor and to establish whether any
supplementary treatment was required. Subsequent to this, changes
in the pain grade and temperature, and results of routine blood and
liver function tests were observed. The patients were examined by
enhanced computed tomography (CT)/magnetic resonance imaging (MRI)
or ultrasound imaging in months 1, 3, 6, 9 and 12 post-treatment. A
follow-up study was performed every 3–6 months.
Results
Baseline data
From a total of 180 patients, 115 were enrolled in
the present study according to the inclusion criteria. A total of
62 patients presented with colon cancer and 53 with rectal cancer.
Highly-differentiated cancer was detected in 10 patients,
moderately-differentiated in 76 and poorly-differentiated in 29.
The patients consisted of 78 males and 37 females. The age range
was between 30 and 86 years old [mean ± standard deviation (SD),
59.46±11.79]. There were 165 ablation lesions, with diameters
ranging between 1.3 and 5.0 cm (mean ± SD, 3.10±1.05 cm); 85
lesions were ablated once and 80 lesions were ablated twice. The
mean (± SD) power level used was 50.3±7.2 W (range, 45–60 W) and
the mean (± SD) duration of treatment was 5.6±2.7 min (range, 2–8
min). Following treatment, the mean (± SD) hospitalization time was
4.69±2.08 days (range, 2–10 days). According to the location of the
liver metastasis, two groups were defined: The colon cancer group
and the rectal cancer group.
Comparison of baseline data between colon
and rectal cancer groups
No significant differences were observed between the
colon and rectal cancer groups with regard to gender, age, number
of lesions, lesion size, pathological differentiation or
hospitalization time following ablation (P>0.05; Table I).
 | Table IComparison of baseline data between
colon and rectal cancer groups. |
Table I
Comparison of baseline data between
colon and rectal cancer groups.
| Parameter | Colon (n=62) | Rectal (n=53) | P-value |
|---|
| Gender, n |
| Male | 38 | 40 | 0.155 |
| Female | 24 | 13 | |
| Age, years | 59.21±13.06 | 59.74±10.21 | 0.806 |
| Number of lesions,
n |
| 1 | 38 | 37 | 0.571 |
| 2 | 18 | 13 | |
| 3 | 6 | 3 | |
| Maximum diameter,
cm | 2.86±0.97 | 3.1±60.86 | 0.086 |
| Pathological
differentiation, n |
| High | 5 | 5 | 0.593 |
| Moderate | 39 | 37 | |
| Poor | 18 | 11 | |
| Hospitalization time,
days | 4.73±2.51 | 4.41±2.69 | 0.355 |
Comparison of recurrence and cumulative
survival rates between colon and rectal cancer groups
Up to May 2013, the patients had been followed up
for 28 months (median follow-up time; range, 12–48). A total of 5
cases were lost to follow up, with a rate of 4.35%. Subsequent to
ablation, 13 cases exhibited intrahepatic lesions, 14 cases
exhibited new liver lesions and 23 cases manifested other organ
metastases. In total, 14 patients succumbed; 9 due to respiratory
failure, 4 due to failure of liver function and 1 due to cerebral
hemorrhage. The cumulative recurrence rates were 27.8, 48.4 and
59.3% and the cumulative survival rates were 98.1, 87.1 and 78.7%
in years 1, 2 and 3 years post-treatment, respectively. No
significant differences were observed between the cumulative
recurrence and cumulative survival rates between the two groups
(P>0.05) (Table II).
| Table IIComparison of recurrence rate and
mortality rate between colon and rectal cancer groups. |
Table II
Comparison of recurrence rate and
mortality rate between colon and rectal cancer groups.
| Recurrence rate | Cumulative survival
rate |
|---|
|
|
|
|---|
| Group | 1-year | 2-year | 3-year | 1-year | 2-year | 3-year |
|---|
| Colon, % | 30.0 | 48.1 | 61.1 | 98.4 | 88.6 | 78.7 |
| Rectal, % | 36.0 | 49.7 | 57.5 | 97.9 | 85.8 | 78.6 |
| P-value | 0.441 | 0.908 | 0.749 | 0.546 | 0.744 | 0.812 |
Major adverse reactions following
ablation
Following ablation, adverse reactions were mainly
recorded as regional pain, fever and hepatic insufficiency. The
pain grade was recorded between the 4th and 6th degree following
treatment in 23 patients. The body temperature of 35 patients was
>38°C, with the longest period at this temperature recorded as
lasting for 5 days. A total of 5 cases required thoracocentesis and
drainage for pleural effusions (3 patients with colon cancer and 2
with rectal cancer). No significant difference was observed in the
white blood cell count, alanine aminotransferase level, presence of
fever, time >38°C or pain grade between the two groups
(P>0.05). Additionally, no patients suffered hepatic abscesses,
peritonitis, other infections or succumbed to the treatment. The
principal adverse reactions of the colon and rectal cancer groups
following ablation are shown in Table
III.
| Table IIIComparison of adverse reaction between
two groups. |
Table III
Comparison of adverse reaction between
two groups.
| Parameter | Colon (n=62) | Rectal (n=53) | P-value |
|---|
| WBC on 1st day,
×109/l | 9.36±3.65 | 8.44±3.62 | 0.182 |
| ALT on 1st day,
U/l | 171.45±103.65 | 195.59±122.18 | 0.254 |
| Fever |
| None | 19 | 15 | 0.884 |
| <38°C | 24 | 22 | |
| ≥38°C | 19 | 16 | |
| Time >38°C,
days | 0.87±1.38 | 0.78±1.24 | 0.748 |
| Pain grade |
| 0 | 35 | 32 | 0.839 |
| 1–3 | 14 | 11 | |
| 4–6 | 13 | 10 | |
Discussion
The disease incidence of colorectal cancer is high,
and 40–50% of colorectal cancer patients will develop liver
metastases (9). Currently, the main
way to treat CRLM is via excision. The 5-year survival rate can
reach 30–40%, however, only 20% of patients with liver metastases
can be completely cured (10).
Patients with unresectable CRLM have previously been shown to live
on average for only 8–10 months without treatment, with a 5-year
survival rate of <5%. With the application of chemotherapeutics
and new target drugs, this survival rate has been shown to be
enhanced to 20–24 months, and a few of the CRLM patients in whom it
was first believed that excision could not be performed have been
found to be able to withstand a resection with curative intent
(11,12). However, following chemotherapy, the
condition of the patients generally changes. Minimally invasive
treatment has become a reasonable choice for the majority of
patients who reject liver tumor resection.
In the past two decades, ultrasound-guided minimally
invasive treatment has developed so fast that transarterial
chemoembolisation (TACE) and thermal ablation therapy have become
widely used. TACE is used merely as a palliative therapy when CRLM
cannot be excised or the patient rejects surgery (13). However, thermal ablation therapy has
become one of the main therapies to cure CRLM, and RFA has been a
more recent alternative treatment method. RFA is able to excise a
single CRLM (diameter, <3 cm) and has an effect equal to that of
direct excision. Moreover, with regard to the small tumors that are
difficult to reach and hide in the depths of the liver, RFA, to a
certain extent, can treat CRLM better than direct excision
(14,15). As is shown by a number of studies of
RFA on unresectable CRLM, the 3-year survival rates range between
37 and 77%, while the 5-year rates are between 27 and 36% (16–18).
Due to intrahepatic micrometastases and incomplete tumor
destruction, the use of RFA is associated with the risk of
intrahepatic and local disease recurrence (19). Certain studies of liver recurrence
patterns for CRLM following RFA have indicated intrahepatic
recurrence rates of between 32 and 62.5% (14,20–22).
Compared with RFA, MWA has the merit of faster local
heating and a wider range of ablation zone (23,24).
MWA can be used with multiple probes rendering larger tissues down
in size in a shorter time. Due to active heating, MWA, unlike RFA,
is not affected by charred and desiccated tissue at the tip of the
probe, leading to more uniform and reliable tissue ablation zones
(25). This study has a short
follow-up period and the patients should continue to be followed up
until a 5-year survival rate may be calculated.
The principal adverse reactions following ablation
are low-grade local pain and fever, which can be relieved following
expectant treatment (24).
Inflammatory reactions and hepatic insufficiency may be caused by
absorption of intrahepatic tumor necrosis, which may be recovered
from within 2–7 days. Following ablation, pleural effusion, which
is associated with a small distance between ablation lesions and
diaphragmatic muscle, can be absorbed automatically by the body or
be drained by surgery (26).
Noticeably, another concurrent disease, tumor metastasis in the
needle tract, should be protected against by way of extraction from
the original tract and by heating the tract (27). Neither implantation metastases nor
serious infections and mortality are associated with MWA. Unlike
surgery, MWA has the advantages of less concurrent diseases, a fast
recovery and a higher quality of life.
The limitations of the present study included the
fact that the data was only from one center, involved few cases,
has a short follow-up time and does not contain a comparison with
other therapies. To conclude, although ultrasound-guided
percutaneous MWA is a safe and competent way to treat inoperable
colorectal cancer in liver metastases, the conclusions require
elucidation by a multicenter randomized controlled study.
Acknowledgements
This study is financially supported by the Ministry
of Science and Technology Support Program (no. 2013BAI01B01) and
the Ministry of Science and Technology international cooperation
projects (no. 2012DFG32070).
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