TITLE PAGE
Title: Ultrasound findings of Early Cholangiocarcinoma in Risk group in Endemic area of Opisthorchis
viverrini.
Authors: Jidapa Stapornchaisit1
Affiliations:
1
Department of Radiology, Faculty of Medicine, Khon Kaen University, Thailand
Corresponding authors:
Name:
Jidapa Stapornchaisit
Address: Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002,
Thailand
Telephone: +66Fax:
e-Mail:
ryoma.tas@gmail.com
Type of contribution:
Original research results
Running title:
Ultrasound findings of Early Cholangiocarcinoma in Risk group in
Endemic area of Opisthorchis viverrini
Number of words in the abstract:
268
Number of words in the text:
x,xxx
Number of tables:
x
Number of figures:
x
1
ABSTRACT
Background: Cholangiocarcinoma (CCA) is the highest prevalent cancer in northeastern
Thailand without yet specific tools or clinical for screening in early stage. Ultrasound is
considered our most useful screening tool. However, not much study had been done to
determine the common early ultrasound findings of the section proven CCA cases in large
risk group population.
Objective: To identify the common ultrasound findings of early cholangiocarcinoma cases in
risk population living in endemic area of Opisthorchis viverrini.
Methods: We also collected ultrasonographic findings data from the Cholangiocarcinoma
Screening and Care Program(CASCAP) which is the largest-ever study performed in
cholngiocarcinoma risk population, in terms of type of abnormal findings and associated
parenchymal background in cases with confirmed diagnosis by further investigation imaging
and pathological report.
Results: In total of 536 cases found in 46,983 screening individuals, ?.??%(n=???) are
confirmed to be cholangiocarcinoma by pathological report, ?.??%(n=???) are confirmed to
be cholangiocarcinoma by further investigation including CT and MRI?.??%(n=???) are other
malignancies, ?.??%(n=???) are benign and ?.??%(n=???) do not receive further investigation
due to various reasons. ??% of the confirmed cases are in early stage cholangiocarcinoma and
??% are in late stage. Among ??? confirmed cholangiocarcinoma cases, ?.??%(n=???) are
found in periductal fibrosis parenchyma, ?.??%(n=???) in normal parenchyma,
?.??%(n=???)in fatty liver parenchyma and ?.??%(n=???) in cirrhotic parenchyma. The
mass-forming characteristic is accounted for ??%(n=???) of confirmed cholangiocarcinioma
cases and biliary dilatation is ??%(n=???). ??% (n=???) have both mass-forming and biliary
dilatation findings.
Conclusions: The most common ultrasound finding found in cholangiocarcinoma patients
with histological proven is.............. and the most common parenchyma background in
cholangiocarcinoma cases is................................. Further studies in term of predictive value
for each finding are needed.
Keywords: Cholangiocarcinoma, Ultrasound
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INTRODUCTION
The number of patients with cholangiocarcinoma tends to rise every year worldwide
(1-5). Thailand is the country with highest incident rate of cholangiocarcinoma especially in
the northeastern region(6). The major risk factor is liver fluke infection such as Opisthorchis
viverrini and Clonorchis sinensis (7). Patients are usually asymptomatic and are usually
diagnosed at late-stage of the disease where rate for curative treatment is only 21.6%. Early
diagnosis and treatment are necessary to improve the outcome of the treatment(8).
Ultrasound is a valuable screening modality to choose patients for further imaging
with accuracy of 88% in benign diseases and 88% in malignant diseases(9). It has proven to
have early CCA detection and surveillance role in endemic area of Opisthorchis viverrini(10).
Some study had mentioned about ultrasound screening in group of people in endemic area
(11) but never before had ultrasound screening been implement in large scale screening of
population at risk.
This study is aim to identify ultrasound characteristics of early cholangiocarcinoma
cases in risk group with pathological proof.
MATERIALS AND METHODS
Ethical consideration
This study was conduct according to the International Conference of Harmonization
(ICH) Good Clinical Practice (GCP) guideline and the Declaration of Helsinki. The final
study protocol and the final version of the Written Informed Consent had been approved by
Khon Kaen University Ethic Committee. This study was registered at Thai Clinical Trial
Registry (TCTRXXXXXX).
Population
This study is a retrospective descriptive study of asymptomatic patients enrolled in
Cholangiocarcinoma Screening and Care Program (CASCAP, see details at
www.cascap.in.th) for ultrasound surveillance. In cases that abnormal findings were reported,
the patients were then sent for further investigation and surgery if indicated. We collected
data of those cases with available pathological proven CCA and looked back to the
ultrasound findings found in early ultrasound screening.
Ultrasound findings
The ultrasound images available of the confirmed diagnosis cases were review by 2
gastrointestinal radiologists with … and …. years of experience in gastrointestinal imaging.
The reviewers will be blinded from clinical, previous ultrasound report, further investigation
report and pathological report. Three aspects of liver and biliary system will be reviews. First
parenchymal echo, the reviewers will grade into normal parenchyma and abnormal
parenchyma, the abnormal result will be classified into fatty liver, periductal fibrosis(PDF)
and cirrhosis. Second liver mass, the reviewers will categorized our cases into no mass,
hypoechoic mass, hypoechoic mass, mixed echoic mass and anechoic mass. And finally
dilatation of biliary system will be noted if presented.
Pathological reports
The pathological reports are sent from various centers depended on the hospital that
operated on the CCA cases. The reports are classified as CCA, non CCA malignancy and
benign diseases.
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Statistical analysis
Descriptive statistics was used to evaluate the conduct of the study. Overall study
algorithm was presented as a CONSORT diagram (Consolidated Standards of Reporting
Trial). Baseline characteristics of the patients were examined using descriptive statistics.
Mean and standard deviation were used for continuous variables and frequency counts and
percentage were for categorical variables.
All statistical analyses were implemented using Stata 13 (StataCorp, College Station,
TX).
RESULTS
Table 1. Patient characteristics presented as number and percentage unless specified
otherwise
Characteristics
Number
Percentage
Total
Gender
Male
Female
Mean age ± SD(years)
Receive further CT/MRI
CT
MRI
Do not receive further CT/MRI
With pathological proof
Without pathological proof
Table 2. Ultrasound findings in cholangiocarcinoma cases present in number and percentage
unless specified otherwise
Ultrasound characteristics
Number
Percentage
Parenchymal echo
Normal
Abnormal
Fatty liver
PDF
Cirrhosis
Liver mass
Absent
Present
High echo
Low echo
Mixed echo
An echo
Dilated bile duct
Absent
Present
Right lobe
Left lobe
Common bile duct
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Figure 1. Algorithm of the study
All patients enroll in CASCAP database
(n =82,922)
All patients underwent ultrasound screening
(n =46,983)
Cases with positive ultrasound findings
(n = 562)
Cases with pathological proven CCA
(n=xxx)
Excluded (n=xx)
- No further investigation(n=x)
- No pathological proof(n=x)
- Benign patho(n=x)
- Non CCA malignant patho(n=x)
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DISCUSSIONS
Explaining the findings
<copy narrative parts of the Results followed by explaining each important findings in
turn , 5-10 references needed here in this section where about half of them are the same as the
one cited in the Introduction section of the manuscript>





Strength of the study
The data of study is from the largest ultrasonographic screening in risk population
ever performed.
All the cases included in this study have pathological proof of cholangiocarcinoma.
Limitation of the study
Ultrasound is an operator dependent tool, so variation of experience of the performers
is the limitation of this study.
Not all ultrasound images are available for retrospective review by experience
radiologist.
Many patients denied further investigation or surgery, making the number of
pathological proven became lower.
Conclusions
In this study we found that in confirmed cases of CCA, ……….is the most common
ultrasound finding and ………..is the most common parenchymal background.
Recommendations
Further studies in terms of positive predictive value of each finding are needed to
confirm the benefit of ultrasound in screening for early CCA.
ACKNOWLEDGEMENTS
The authors thank to all patients for their valuable participations, to members of the
Cholangiocarcinoma Screening and Care Program (CASCAP) for their efforts in operating
the project, and to members of the Data Management and Statistical Analysis Center
(DAMASAC) for their supports in data management and analysis. Both CASCP and
DAMASAC were supported to handle this project by the Faculty of Medicine and the Faculty
of Public Health, Khon Kaen University. CASCAP was implemented under a memorandum
of understanding between Ministry of Public Health, Ministry of Education, and Ministry of
Interior. CASCAP was also supported by the Cholangiocarcinoma Foundation of Thailand.
POTENTIAL CONFLICT OF INTEREST
This study was financially supported by the Cholangiocarcinoma Foundation of Thailand. All
authors reported no conflicts of interest.
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