Evidence base and patients' perspective - World Journal of ...

INTRODUCTION
Hepatocellular carcinoma (HCC) is the third leading cause
of cancer-related death in the world, and the ninth leading
cause of cancer deaths in the United States [1-7] . The
number of deaths per year from HCC is virtually identical
to the incidence throughout the world, underscoring
the high fatality rate of this aggressive disease [8] . The sole
approach to achieve long-term survival is to detect the
tumor at an early stage, when effective therapy can be
applied [9] . Accordingly, the European Association for the
Study of the Liver and the American Association for the
Study of Liver Diseases recommend performing screening
for HCC in patients at risk who would be treated if
diagnosed with this condition [10-12] . Under these guidelines,
imaging criteria for the diagnosis of HCC are established
for lesions 1 cm or larger in patients at risk, but owing to
a high false-positive rate, a wait-and-see policy is recommended
for nodules smaller than 1 cm in diameter [11,12] .
However, the possibility remains high that minute hepatic
nodules detected during surveillance may become malignant
over time [13,14] . In addition, a delay in the start of
treatment of early-stage HCC may be associated with a
poorer patient survival [15] . Nevertheless, clinicians have
limited data on the clinical course of sub-centimeter-sized
nodules (SCSNs) detected during surveillance.
A variety of important risk factors for the development
of HCC have been identified. These include chronic
hepatitis B and C virus infection and cirrhosis due to almost
any cause [16-22] . Almost 80% of cases are due to underlying
chronic hepatitis B and C virus infection [17] . Since
patients with chronic hepatitis B who may not have fully
developed cirrhosis or have regressed cirrhosis as well as
patients with cirrhosis are at increased risk of developing
HCC, an updated the American Association for the Study
of Liver Diseases guidelines recommended surveillance
in patients with chronic hepatitis B [12] .
The purpose of our study was to evaluate the outcome
of SCSNs detected during HCC surveillance in
patients at risk and to determine the risk factors for development
of those nodules into HCC.
MATERIALS AND METHODS
Patients
This retrospective study was conducted according to the
principles of the Declaration of Helsinki. The study involved
patients with liver cirrhosis of any etiology or
chronic liver disease including chronic hepatitis B and C
virus infection, without a prior history of HCC in whom
a SCSN was detected during HCC surveillance with ultrasonography
(US) or computed tomography (CT) of
the liver at Samsung Medical Center, Seoul, South Korea
between January 1, 2005 and April 30, 2005 (n = 198). At
our institution, patients at risk for HCC were followed
with alpha-fetoprotein (AFP) and US every 6 mo. In case
of a difficult US, such as in obese individuals, CT and
US were performed alternately for HCC surveillance.
WJG|www.wjgnet.com
Min YW et al . Sub-centimeter-sized hepatic nodules
Even when an SCSN was detected, patients were usually
followed with AFP and US every three or six mo as appropriate.
However, if any SCSN enlarged or its appearance
was typical of HCC, 3 mo surveillance was used for
a certain period or other image modalities such as CT
or magnetic resonance imaging (MRI) were performed
additionally. The medical records of all patients were
reviewed thoroughly. Patients who met any of the following
criteria were excluded: (1) less than 12 mo of followup,
except subjects who were diagnosed with HCC within
12 mo of follow-up; (2) subjects who were lost to followup
and diagnosed with HCC at an outside hospital; and (3)
any history of cancer. Thus, a total of 56 patients were
excluded from the study. Forty patients had less than 12
mo of follow-up, seven patients were excluded because
HCC was diagnosed at the time of inclusion in the study,
and three patients were lost to follow-up. Additionally,
three patients had hepatic nodules 1 cm or larger in size
at inclusion, two patients had other types of cancer, and
the etiology of liver disease in one patient was unclear.
Data collection
The following clinical and laboratory information was
collected from each patient: age, sex, etiology of liver
disease, presence of liver cirrhosis, the Child-Pugh classification,
aspartate aminotransferase (AST), alanine aminotransferase
(ALT), prothrombin time (PT), serum total
bilirubin, platelet count, serum albumin, and baseline and
follow-up AFP levels.
Image interpretation
The initial radiologic diagnosis of SCSNs was based on
the results of US or CT during surveillance. In addition,
all radiologic images were reviewed by one radiologist
who had 11 years of experience in liver imaging interpretation.
He did not participate in the initial patient selection
and was blinded to the final diagnoses and clinical
information such as AFP levels. Each detected lesion was
evaluated for the number, location, and echogenicity/attenuation
of nodules. Lesions were categorized as follows:
(1) hypoechoic/low-attenuation; (2) hyperechoic/highattenuation;
and (3) mixed echoic/attenuation (Figure 1).
All lesions were included in one of these three categories.
The diagnosis of HCC was based either on biopsy
or the clinical criteria of the Korean Liver Cancer Study
Group and the National Cancer Center, South Korea [3] .
Briefly, the diagnosis of HCC was made when the AFP
level was ≥ 400 ng/mL and at least one of the dynamic
enhancement CT or MRI showed a vascular pattern typical
of HCC in patients at risk including patients with
HBV or HCV infection, or liver cirrhosis. If the AFP
level was < 400 ng/mL, at least two of the dynamic enhancement
CT, MRI or transarterial angiography must
show vascular patterns typical of HCC in order to make
a diagnosis of HCC.
Statistical analysis
Statistical analyses were conducted using PASW Statistics
2655 June 7, 2012|Volume 18|Issue 21|