1
(Mock manuscript No.1: Cluster analysis of the ultrasound findings)
Large scale ultrasonography screening for cholangiocarcinoma in
northeastern Thailand: a cluster analysis
Nitaya Chamadol MD, Narong Khantikeo MD, Puangrat Yongvanit PhD, Watcharin Loilome
PhD, Nisana Namwat PhD, Cameron Hurst PhD, Ross Andrew PhD, Trevor Petney PhD, Bandit
Thinkhamrop PhD.
Abstract
Background: Cholangiocarcinoma (CCA) is one of the most fatal cancer and reported as the
world’s highest rate among natives of the northeastern Thailand. Ultrasonography findings of the
livers of population at the high risk to CCA might offer ways for future studies.
Objective: To describe pattern of abnormalities of ultrasonography findings of the liver among
population at the high risk to CCA in northeastern Thailand.
Methods: This reported results from the baseline screening for CCA as of August 2014 of an
ongoing project- the Cholangiocarcinoma Screening and Care Program (CASCAP) conducted in
northeastern Thailand, the region known to have the world’s highest rate of cholangiocarcinoma.
Participants were northeasterners who were at least one of the followings: 40 years or older, ever
been infected with liver fluke, ever been treated with praziquantel, or ever been consumed raw
fresh water fish. Ultrasonography were done by well-trained medical radiologists. This study has
been approved by Khon Kaen University Ethic Committee and registered at Thai Clinical Trial
Registry (TCTRXXXXXX).
Results: Of 35,577 participants, xx.x% were male with a mean age of xx.x (standard deviation =
x.x) years. There were xx,xxx (xx.x%) participants found to have at least one abnormalities.
Majority of them, xxx (xx.x%), had peripheral bile duct and xx (x.x%) had fatty liver. Those
who had either one or both of these abnormalities shared about one third of all screened
population (xx.x%). The most common combination of the abnormalities was ???? (xx.x%)
followed by ???? (xx.x%) and ???? (xx.x%). Proportion of liver mass was xx.x% and of bile duct
dilatation was xx.x%. Cluster analysis revealed that there were x dominant and distinctive
clusters of ultrasonography findings including ????. The prevalence of these subgroup were
xx.x%, xx.x%, xx.x%, and xx.x% respectively.
Conclusion: One third of risk population in northeastern Thailand had either peripheral bile duct
or fatty liver. These shared almost all abnormalities of the livers. The data suggested that ???
Keywords: cholangiocarcinoma, ultrasonography screening, periductal fibrosis, fatty liver,
cluster analysis
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INTRODUCTION
Cholangiocarcinoma (CCA) is the one of the most fatal cancer and reported as the world’s
highest rate among natives of the northeastern Thailand. Ultrasonography of the liver allowed
detection of liver mass and bile duct dilatation which are findings of suspected CCA to be
referred for further investigation for early stage CCA. However, the findings in large scale
population screening have never been reported.
<More to be written>
METHODS
Design overview
This reported results from the baseline screening for CCA as of August 2014 of an ongoing
project- the Cholangiocarcinoma Screening and Care Program (CASCAP, see details at
www.cascap.in.th). Northeastern Thailand has long been known to be the region with the world’s
highest rate of cholangiocarcinoma.
Participants were northeasterners who were at least one of the followings: 40 years or older, ever
been infected with liver fluke, ever been treated with praziquantel, or ever been consumed raw
fresh water fish. Ultrasonography were done by well-trained medical radiologists.
Ethical consideration
This study will be 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).
Statistical analysis
Baseline characteristics of the participants were examined using descriptive statistics. Percent
descriptions of abnormalities of the liver based on ultrasonography findings were presented.
Cluster analysis was used to identify subgroup of the abnormality. All statistical analyses were
implemented using Stata 13 (StataCorp, College Station, TX).
3
RESULTS
Table 1. Baseline characteristics presented as number and percentage unless specified otherwise
Characteristics
Mean age  SD (years)
Age group
Less than 50
50 – 60
Greater than 60
Education
No formal education
Primary school
Secondary school
Tertiary school
Collage
Under graduate
Post graduate
Occupation
Unemployed
Farmer
Labor
Own business
Government/State enterprise
Others
Ever been infected with liver fluke
Never been tested
Tested and found to be positive
Tested and found to be negative
Cannot remember
Ever been treated with praziquantel
Never been treated
1 occasion
2 occasions
3 occasions
More than 3 occasions
Cannot remember
Having relatives with cholangiocarcinoma
No
Yes
Relatives with cholangiocarcinoma
Grandparent (Paternal)
Grandparent (Maternal)
Uncle/Aunt (Older)
Total
Number (%)
xx.x  x.x
Male
Number (%)
xx.x  x.x
Female
Number (%)
xx.x  x.x
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
4
Characteristics
Uncle/Aunt (Younger)
Parents
Son/Daughter
Sibling
Nephew/Niece
Spouse
Smoking
No
Yes, either current or previous
Alcohol consumption
No
Yes, either current or previous
Alcoholic toxicity
No
Yes, either current or previous
Ever eaten uncooked or fermented fish
(specifically, fresh water with scales)
No
Yes, either current or previous
Underlying diseases
None
Hepatitis B
Hepatitis C
Diabetes
Others
Total
Male
Female
Number (%) Number (%) Number (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
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Figure 1. Summary of ultrasonography findings
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Table 2. Findings of ultrasonography screening
Characteristics
Total
Number (%)
Male
Number (%)
Female
Number (%)
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
xx
xx
xx
xx
(xx.x)
(xx.x)
(xx.x)
(xx.x)
Patterns of ultrasound findings
PDF
Fatty liver
Cirrhosis
Mass
0
0
0
0
1
0
0
0
0
1
0
0
0
0
1
0
0
0
0
1
0
0
0
0
1
1
0
0
1
1
1
0
1
1
1
1
1
1
1
1
1
0
1
1
1
1
0
1
1
1
1
0
1
1
1
1
1
0
0
1
1
0
0
0
...
Fatty liver sub-categories
None
Mild
Moderate
Severe
Periductal fibrosis sub-categories
None
PDF 1
PDF 2
PDF 3
Liver mass sub-categories
None
Single mass
Multiple mass
Size of greater than 5 cm.
Dilated bile duct sub-categories
None
Right lobe
Left lobe
Common bile duct
Gall bladder
Normal
Wall thickening
Duct dilatation
0
0
0
0
0
1
0
0
0
1
1
1
1
0
1
1
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
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Characteristics
Wall polyp
Wall mass
Gall stone
None
Single
Multiple
Total
Male
Female
Number (%) Number (%) Number (%)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
Figure 2. Cluster analysis of findings of ultrasonography screening
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.x)
xx (xx.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
<to be written>
Limitation of the study



Can selection bias distort the findings?
Can information bias distort the findings?
Can confounding bias distort the findings?
Conclusions
(copy from the Conclusion section of the abstract then add some)
Recommendations
<to be written>
ACKNOWLEDGEMENTS
The authors thank to ???.
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POTENTIAL CONFLICT OF INTEREST
This study was financially supported by the Cholangiocarcinoma Foundation of Thailand. All
authors reported no conflicts of interest.
REFERENCE
<To be written>