Search

Narong Khuntikeo,1 Attapol Titapun,1 Nittaya Chamadol,2 Wuttisak Boonphongsathien,2 Prakasit Sa-Ngiamwibool,3 Simon D Taylor-Robinson,4 Christopher A Wadsworth,4 Shuo Zhang,5 Evdokia M Kardoulaki,6 Richard RA Syms6 1Department. of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand; 2Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; 3Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; 4Division of Surgery and Cancer, Imperial College London, Paddington, London W2 1NY, UK; 5Philips Healthcare Germany, Health Systems, Clinical Science, Hamburg, Germany; 6EEE Department, Imperial College, London SW7 2AZ, UKCorrespondence: Simon D Taylor-RobinsonDivision of Surgery and Cancer, Imperial College London, Liver Unit, St. Mary’s Hospital, South Wharf Road, Paddington, London W2 1NY, UKTel +44 20 3312 6199Email s.taylor-robinson@imperial.ac.ukAim: Diagnostic imaging of early-stage cholangiocarcinoma is challenging. A previous in vitro study of fixed-tissue liver resection specimens investigated T2 mapping as a method of exploiting the locally increased signal-to-noise ratio (SNR) of duodenoscope coils for improved quantitative magnetic resonance imaging (MRI), despite their non-uniform sensitivity. This work applies similar methods to unfixed liver specimens using catheter-based receivers.Methods: Ex vivo intraductal MRI and T2 mapping were carried out at 3T on unfixed resection specimens obtained from cholangiocarcinoma patients immediately after surgery using a catheter coil based on a thin-film magneto-inductive waveguide, inserted directly into an intrahepatic duct.Results: Polypoid intraductal cholangiocarcinoma was imaged using fast spin-echo sequences. High-resolution T2 maps were extracted by fitting of data obtained at different echo times to mono-exponential models, and disease-induced changes were correlated with histopathology. An increase in T2 was found compared with fixed specimens and differences in T2 allowed the resolution of tumour tissue and malignant features such as polypoid morphology.Conclusion: Despite their limited field of view, useful data can be obtained using catheter coils, and T2 mapping offers an effective method of exploiting their local SNR advantage without the need for image correction.Keywords: Cholangiocarcinoma, T2 mapping, catheter coil

Narong Khuntikeo, 1 Attapol Titapun, 1 Nittaya Chamadol, 2 Wuttisak Boonphongsathien, 2 Prakasit Sa-Ngiamwibool, 3 Simon D Taylor-Robinson, 4 Christopher A Wadsworth, 4 Shuo Zhang, 5 Evdokia M Kardoulaki, 6 Ian R Young 6,†, Richard RA Syms 6 1Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; 2Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; 3Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; 4Division of Surgery and Cancer, Imperial College London, Liver Unit, St. Mary’s Hospital, London W2 1NY, UK; 5Philips Healthcare Germany, Health Systems, Clinical Science, Hamburg 22335, Germany; 6EEE Department, Imperial College, London SW7 2AZ, UK†Ian R Young passed away on September 27, 2019Correspondence: Simon D Taylor-RobinsonDivision of Surgery and Cancer, Imperial College London, Liver Unit, St. Mary’s Hospital, South Wharf Road, Paddington, London W2 1NY, UKTel +44 20 3312 6199Email s.taylor-robinson@imperial.ac.ukAim: Cholangiocarcinoma is endemic in southeast Asia, generally developing from liver fluke infestation. However, diagnostic imaging of early-stage disease is challenging. The aim of this work is to investigate relaxometry (specifically, T2 mapping) as a method of exploiting the higher signal-to-noise ratio (SNR) of internal coils for improved reception of magnetic resonance signals, despite their non-uniform sensitivity.Methods: Ex vivo T2 mapping was carried out at 3T on fixed resection specimens from Thai cholangiocarcinoma patients using an mGRASE sequence and an endoscope coil based on a thin-film magneto-inductive waveguide and designed ultimately for internal use.Results: Disease-induced changes including granulomatous inflammation, intraepithelial neoplasia and intraductal tumours were correlated with histopathology, and relaxation data were compared with mono- and bi-exponential models of T2 relaxation. An approximately 10-fold local advantage in SNR compared to a 16-element torso coil was demonstrated using the endoscope coil, and improved tissue differentiation was obtained without contrast agents.Conclusion: The performance advantage above follows directly from the inverse relation between the component of the standard deviation of T2 due to thermal noise and the SNR, and offers an effective method of exploiting the SNR advantage of internal coils. No correction is required, avoiding the need for tracking, relaxing constraints on coil and slice orientation and providing rapid visualization.Keywords: cholangiocarcinoma, T2 mapping, internal coil

Intraductal T2 mapping based on a catheter receiver is proposed as a method of visualizing the extent of intraductal and periductal cholangiocarcinoma (CCA). Compared to external receivers, internal receivers provide locally enhanced signal-to-noise ratios by virtue of their lower field-of-view for body noise, allowing smaller voxels and higher resolution. However, inherent radial sensitivity variation and segmentation for patient safety both distort image brightness. We discuss simulated T2 weighted images and T2 maps, and in vitro images obtained using a thin film catheter receiver of a freshly resected liver specimen containing a polypoid intraductal tumor from a patient with CCA. T2 mapping provides a simple method of compensating non-uniform signal reception patterns of catheter receivers, allowing the visualization of tumor extent without contrast enhancement and potentially quantitative tissue characterization. Potential advantages and disadvantages of in vivo intraductal imaging are considered., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Syms, Wadsworth, Kardoulaki, Titapun, Boonphongsathien, Sa-Ngiamwibool, Zhang, Taylor-Robinson, Chamadol and Loilome.)

Background: Cholangiocarcinoma (CCA) is a highly fatal tumor, and the most favorable chance for long-term survival lies in curative resection. Periductal fibrosis (PDF), a precancerous condition associated with chronic inflammation of the bile ducts, can serve as a screening marker for CCA using hepatobiliary ultrasonography (US). However, limited studies have explored the relationship between PDF and CCA. This study aimed to investigate the association between PDF and CCA in a population at risk in Northeast Thailand., Methods: The study included participants enrolled in the Cholangiocarcinoma Screening and Care Program (CASCAP) between 2013 and 2021 who underwent US. Histological evaluations were conducted following the standard protocol of the tertiary hospital at Khon Kaen University, Thailand. PDF was defined as the presence of fibrosis in the peripheral (PDF1), segmental (PDF2), or main bile duct (PDF3), diagnosed by well-trained general practitioners or radiologists. The association between PDF and CCA was assessed using multiple logistic regression, calculating adjusted odds ratios (AORs) and 95% confidence intervals (CIs)., Results: Out of 751,061 participants, the overall prevalence of PDF was 115,267 (15.35%), with an overall CCA rate of 0.11%. The rates of CCA were 0.1%, 0.15%, and 0.27% in participants with PDF1, PDF2, and PDF3, respectively. After adjusting for gender, age at enrollment, education levels, history of O. viverrini infection, smoking, and alcohol consumption, the AORs for CCA were 0.94 (95% CI: 0.74 - 1.20), 1.4 (95% CI: 1.03 - 1.91), and 2.52 (95% CI: 1.38 - 4.58) for participants with PDF1, PDF2, and PDF3, respectively., Conclusion: Our findings demonstrate a significant association between fibrosis of the segmental and main bile ducts (PDF2 and PDF3) and CCA, with the strongest association observed in participants with PDF3. Hepatobiliary US screening could serve as a valuable tool for early detection of CCA, enabling timely curative treatment.

Background: The liver fluke Opisthorchis viverrini (OV), which subsequently inhabits the biliary system and results in periductal fibrosis (PDF), is one of the primarily causes of cholangiocarcinoma (CCA), a bile duct cancer with an exceptionally high incidence in the northeast of Thailand and other Greater Mekong Subregion (GMS) countries. Insights in fecal metabolic changes associated with PDF and CCA are required for further molecular research related to gut health and potential diagnostic biological marker development., Methods: In this study, nuclear magnetic resonance (NMR) metabolomics was applied for fecal metabolic phenotyping from 55 fecal water samples across different study groups including normal bile duct, PDF and CCA groups., Results: By using NMR spectroscopy-based metabolomics, fecal metabolic profiles of patients with CCA or PDF and of individuals with normal bile duct have been established with a total of 40 identified metabolites. Further multivariate statistical analysis and hierarchical clustering heat map have demonstrated the PDF- and CCA-specific metabotypes through various altered metabolite groups including amino acids, alcohols, amines, anaerobic glycolytic metabolites, fatty acids, microbial metabolites, sugar, TCA cycle intermediates, tryptophan catabolism substrates, and pyrimidine metabolites. Compared to the normal bile duct group, PDF individuals showed the significantly elevated relative concentrations of fecal ethanol, glycine, tyrosine, and N -acetylglucosamine whereas CCA patients exhibited the remarkable fecal metabolic changes that can be evident through the increased relative concentrations of fecal uracil, succinate, and 5-aminopentanoate. The prominent fecal metabolic alterations between CCA and PDF were displayed by the reduction of relative concentration of methanol observed in CCA. The metabolic alterations associated with PDF and CCA progression have been proposed with the involvement of various metabolic pathways including TCA cycle, ethanol biogenesis, hexamine pathway, methanol biogenesis, pyrimidine metabolism, and lysine metabolism. Among them, ethanol, methanol, and lysine metabolism strongly reflect the association of gut-microbial host metabolic crosstalk in PDF and/or CCA patients., Conclusion: The PDF- and CCA-associated metabotypes have been investigated displaying their distinct fecal metabolic patterns compared to that of normal bile duct group. Our study also demonstrated that the perturbation in co-metabolism of host and gut bacteria has been involved from the early step since OV infection to CCA tumorigenesis., Competing Interests: The authors declare that they have no competing interests., (© 2023 Treeriya et al.)

Certain life-threatening abnormalities, such as cholangiocarcinoma, in the human biliary tract are curable if detected at an early stage, and ultrasonography has been proven to be an effective tool for identifying them. However, the diagnosis often requires a second opinion from experienced radiologists, who are usually overwhelmed by many cases. Therefore, we propose a deep convolutional neural network model, named biliary tract network (BiTNet), developed to solve problems in the current screening system and to avoid overconfidence issues of traditional deep convolutional neural networks. Additionally, we present an ultrasound image dataset for the human biliary tract and demonstrate two artificial intelligence (AI) applications: auto-prescreening and assisting tools. The proposed model is the first AI model to automatically screen and diagnose upper-abdominal abnormalities from ultrasound images in real-world healthcare scenarios. Our experiments suggest that prediction probability has an impact on both applications, and our modifications to EfficientNet solve the overconfidence problem, thereby improving the performance of both applications and of healthcare professionals. The proposed BiTNet can reduce the workload of radiologists by 35% while keeping the false negatives to as low as 1 out of every 455 images. Our experiments involving 11 healthcare professionals with four different levels of experience reveal that BiTNet improves the diagnostic performance of participants of all levels. The mean accuracy and precision of the participants with BiTNet as an assisting tool (0.74 and 0.61, respectively) are statistically higher than those of participants without the assisting tool (0.50 and 0.46, respectively (p<0.001)). These experimental results demonstrate the high potential of BiTNet for use in clinical settings., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The chapter discusses the advancement of new imaging techniques, the role of imaging in CCA diagnosis, anatomical and morphological classification, ultrasound screening of CCA, ultrasound findings of MF-CCA, PI-CCA, ID-CCA, the use of CT in CCA diagnosis, staging and treatment planning, CT volumetry and estimation of future liver remnant, post-treatment follow-up and surveillance, MRI imaging, Positron Emission Tomography (PET)/CT, limitations to contrast studies and resolution, internal receivers for CCA imaging, and in vitro imaging of CCA., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The rate of cholangiocarcinoma (CCA) is increasing every year, especially in northeastern Thailand. Screening for CCA using ultrasonography (US) is the fastest technique to identify patients in early stage of CCA development. Currently, few studies have examined patterns of hepatobiliary abnormalities identified using US, which can be indicative of CCA. We aim to evaluate the rate of CCA and its relations to history of US findings. Our study included participants who underwent US and pathological diagnosis of CCA from the Cholangiocarcinoma Screening and Care Program, Northeast Thailand between 2013 and 2020. Data on histological findings were based on the standard protocol of the tertiary hospital at Khon Kaen University. CCA data is categorized into two groups (yes/no) to find the relationship with history of US findings. The adjusted odds ratio (AOR) and their 95% confidence intervals (CI) were used to evaluate the relationship obtained by multiple logistic regression. Of 1880 subjects who underwent US and a pathological diagnosis of CCA, the overall rate of CCA was 35.74%. CCA rate among those with liver mass (LM) was 54.85% and with dilated bile duct (DBD) was 62.01%. The relationship between DBD and CCA was highly significant (AOR = 3.46; 95% CI 2.74-4.36) followed by LM (AOR = 2.28; 95% CI 1.81-2.86) P value < 0.001. Our study reveals that US findings history have a strong association with CCA, especially in people diagnosed with DBD and LM. Therefore, these abnormalities can be indicators for suspected CCA diagnosis through US., (© 2022. The Author(s).)

Background: In Northeast Thailand, Praziquantel (PZQ) is used to treat infection with the Opisthorchis viverrnini (OV). OV has highly prevalence in this area due to the traditional consumption of uncooked cyprinid fish. The nephrotoxic effects of PZQ metabolite excretion through the kidney have not been assessed yet. This study investigated the relationship between number of Praziquantel treatments and kidney parenchymal change., Methods: A study was carried out on participants from the Cholangiocarcinoma Screening and Care Program (CASCAP) between 2013 - 2018. The frequency of PZQ use was reported using a standardized questionnaire. Kidney parenchymal change (KPC) was defined as having a kidney abnormality based on ultrasonography diagnosed by well-trained general practitioners. Adjusted odds ratios (ORs) measured associations between PZQ frequency and KPC controlling for the effects of other extraneous factors using multiple logistic regression., Results: A total of 490,969 subjects with mean age of 55.2 (SD = 9.15) years were enrolled among them 62.1% were female. Prevalence of KPC was 1.2% while prevalence of KPC were 1.2%, 1.3%, 1.4%, and 1.5% for participants with one, two, three, and more than 3 PZQ treatment occasions respectively. Those dose-response relationship was statistically significant based on chi-square test for trend (p-value <0.001). After controlling for possible confounders, compared to non-treatment, subjects with more than 3 treatment occasions were 25% more likely to have a KPC positive result (OR = 1.25; 95% CI: 1.02 - 1.52; p-value = 0.028)., Conclusion: The number of repeated PZQ treatments is statistically significantly related to KPC. This relationship could be included in health messaging for those who continue eating uncooked fish with an understanding that the OV infection can easily be cured by PZQ without any other health concerns. For positive OV cases, however, the known efficacy of PZQ could over-ride the small magnitude of the adverse effect.

Background: Cholangiocarcinoma (CCA) has been categorized based on tumor location as intrahepatic (ICCA), perihilar (PCCA) or distal (DCCA), and based on the morphology of the tumor of the bile duct as mass forming (MF), periductal infiltrating (PI) or intraductal (ID). To date, there is limited evidence available regarding the survival of CCA among these different anatomical and morphological classifications. This study aimed to evaluate the survival rate and median survival time after curative surgery among CCA patients according to their anatomical and morphological classifications, and to determine the association between these classifications and survival., Methods: This study included CCA patients who underwent curative surgery from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand. The anatomical and morphological classifications were based on pathological findings after surgery. Survival rates of CCA and median survival time since the date of CCA surgery and 95% confidence intervals (CI) were calculated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by hazard ratios (HR) and their 95% CIs., Results: Of the 746 CCA patients, 514 had died at the completion of the study which constituted 15,643.6 person-months of data recordings. The incidence rate was 3.3 per 100 patients per month (95% CI: 3.0-3.6), with median survival time of 17.8 months (95% CI: 15.4-20.2), and 5-year survival rate of 24.6% (95% CI: 20.7-28.6). The longest median survival time was 21.8 months (95% CI: 16.3-27.3) while the highest 5-year survival rate of 34.8% (95% CI: 23.8-46.0) occurred in the DCCA group. A combination of anatomical and morphological classifications, PCCA+ID, was associated with the longest median survival time of 40.5 months (95% CI: 17.9-63.0) and the highest 5-year survival rate of 42.6% (95% CI: 25.4-58.9). The ICCA+MF combination was associated with survival (adjusted HR: 1.45; 95% CI: 1.01-2.09; P = 0.013) compared to ICCA+ID patients., Conclusions: Among patients receiving surgical treatment, those with PCCA+ID had the highest 5-year survival rate, which was higher than in groups classified by only anatomical characteristics. Additionally, the patients with ICCA+MF tended to have unfavorable surgical outcomes. Showed the highest survival association. Therefore, further investigations into CCA imaging should focus on patients with a combination of anatomical and morphological classifications.

Background: Acute appendicitis is one of the most common causes of acute abdominal pain requiring emergency intervention. It is often difficult for the clinician to make an accurate diagnosis due to nonspecific and overlapping clinical symptoms. Computed tomography (CT) has become the imaging modality of choice for the evaluation of suspected acute appendicitis. The main purpose of our study was to compare nonenhanced CT (NECT) with contrast-enhanced CT (CECT) for the diagnosis of acute appendicitis., Material and Methods: A total of 140 patients were enrolled in the study. Two abdominal radiologists-masked to both the clinical information and the final diagnosis-retrospectively reviewed the computed tomographic findings and made an imaging diagnosis based on (1) NECT only, (2) CECT only, and (3) both NECT and CECT. With the final diagnosis as the reference standard, the accuracy of each CT technique was estimated., Results: The respective sensitivity, specificity, and accuracy for NECT, CECT, and NECT + CECT for the diagnosis of acute appendicitis were 80.7%, 86.7%, and 84.3%; 86.0%, 81.9%, and 83.6%; and, 87.7%, 80.7%, and 83.6%. There was no significant difference in the diagnosis of acute appendicitis among the 3 techniques. In order to make a correct diagnosis, the presence of at least 3 imaging findings for NECT or at least 4 for CECT had the best diagnostic accuracy. We also found that 9.25 mm was the optimal cut-off threshold for the detection of patients with acute appendicitis., Conclusion: Our study allowed direct comparison between NECT, CECT, and NECT + CECT combined. There was no difference in the ability of each CT technique for diagnosing patients with acute appendicitis. For a patient whom iodinated contrast media is contraindicated or a patient who has an increased risk of severe adverse reaction, we would encourage the use of NECT because it provides comparable diagnostic accuracy without further exposing such patient to the contrast media., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cholangiocarcinoma (CCA) is a serious health challenge with low survival prognosis. The liver fluke, Opisthorchis viverrini, plays a role in the aetiology of CCA, through hepatobiliary abnormalities: liver mass (LM), bile duct dilation, and periductal fibrosis (PDF). A population-based CCA screening program, the Cholangiocarcinoma Screening and Care Program, operates in Northeast Thailand. Hepatobiliary abnormalities were identified through ultrasonography. A multivariate zero-inflated, Poisson regression model measured associations between hepatobiliary abnormalities and covariates including age, sex, distance to water resource, and history of O. viverrini infection. Geographic distribution was described using Bayesian spatial analysis methods. Hepatobiliary abnormality prevalence was 38.7%; highest in males aged > 60 years (39.8%). PDF was most prevalent (20.1% of males). The Standardized Morbidity Ratio (SMR) for hepatobiliary abnormalities was highest in the lower and upper parts of the Northeast region. Hepatobiliary abnormalities specifically associated with CCA were also more common in males and those aged over 60 years and distributed along the Chi, Mun, and Songkram Rivers. Our findings demonstrated a high risk of hepatobiliary disorders in Northeast Thailand, likely associated with infection caused by O. viverrini. Screening for CCA and improvement of healthcare facilities to provide better treatment for CCA patients should be prioritized in these high-risk areas.

Background: Patients with cholangiocarcinoma (CCA) usually have no specific symptoms until an advance stage of the disease and curative treatment is not possible. Patients with early stage, operable disease can be found using ultrasonography (US). A US-screening program was implemented in Thailand where CCA incidence is the highest worldwide. Here we evaluate the effectiveness of the program by comparing the proportion of individuals with early stage CCA in the screening group with that of the walk-in group presenting at hospitals with clinical symptoms., Methods: All patients had a pathological diagnosis of CCA. The difference in the proportions and the 95% confidence interval (CI) were obtained using binomial regression., Results: Of the 762 histologically proven CCA cases, 161 were from the screening group and 601 from the walk-in group. The proportion of early stage CCA (stages 0 to II) diagnosed was 84.5% in the screening and 21.6% in the walk-in groups. After adjustment age, gender, and liver fluke infection, there was a significantly higher proportion (P < 0.001) and higher chance (P < 0.001) of having early stage CCA in the screening group than in the walk-in group., Conclusions: US-screening is an effective tool for detecting early stage, operable CCA in high incidence areas., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Background: Human infection with Opisthorchis viverrini , a carcinogenic liver fluke inhabiting the biliary tree, is endemic in Southeast Asia. Chronic infection is associated with a fatal complication, cholangiocarcinoma (CCA), a late-presenting and aggressive malignancy. Currently, annual mortality rates from CCA mirror trends in incidence, due in part to limited availability of efficient prognostic and early diagnostic biomarkers. With ability to detect thousands of urinary metabolites using metabonomics, the urine metabolome holds great potential in providing an insight into system-level alterations in carcinogenesis and in identifying metabolic markers altered in response to disturbed homoeostasis., Methods: Global molecular profiling using reversed-phase ultraperformance liquid chromatography mass spectrometry was utilised to acquire the urinary spectral profile of 137 Thai subjects (48 at high risk of infection, 41 with O. viverrini infection, 34 periportal fibrosis and 14 CCA) from Khon Kaen, Thailand., Results: Multivariate statistical analysis identified perturbation in several molecular classes related to purine metabolism and lipid metabolism in the CCA urine metabolome. These markers mainly reflect changes in energy metabolism to support proliferation (increased fatty acid oxidation and purine recycling), DNA methylation and hepatic injury., Conclusions: Several metabolites of biological interest were discovered from this proof-of-principle dataset. Augmenting these findings is essential to accelerate the development of urinary metabolic markers in CCA., (© 2019 The Authors.)

Cholangiocarcinoma (CCA) caused by chronic liver fluke infection is a major public health problem in Northeast Thailand. Identification of CCA risk groups is urgently needed for the control of CCA in this region. Periductal fibrosis (PDF) induced by chronic inflammation of bile ducts is known as a pre-neoplastic lesion of CCA. We aimed to identify the serum CCA and PDF biomarkers using mass spectrometry (UPLC-ESI-QqQ) with multiple reaction mode (MRM) analysis. Here, serum levels of serotransferrin glycoforms at the glycopeptide level were measured in the sera of CCA ( n = 100), PDF ( n = 50), and healthy control ( n = 100) subjects. The results indicated that serotransferrin peptide levels were generally the same between the control and PDF groups, whereas CCA patients had reduced levels. Moreover, 56 serotransferrin glycoforms were detected, with nine increased in CCA compared to control subjects. Among them, the serum levels of four glycoforms were increased in PDF and CCA patients compared to control subjects. In particular, highly sialylated multi-branched glycans of serotransferrin serum were significantly correlated with poor prognosis and tumor stage in CCA patients. Taken together, these glycoforms could be used as risk biomarkers and prognosis and diagnosis markers of CCA.

Cholangiocarcinoma (CCA) is a major health problem in northeastern Thailand. The majority of CCA cases are clinically silent and difficult to detect at an early stage. Although abdominal ultrasonography (US) can detect premalignant periductal fibrosis (PDF), this method is not suitable for screening populations in remote areas. With the goal of developing a blood test for detecting CCA in the at-risk population, we carried out serum protein biomarker discovery and qualification. Label-free shotgun proteomics was performed on depleted serum samples from 30 participants ( n = 10 for US-normal, US-PDF, and CCA groups). Of 40 protein candidates selected using multiple reaction monitoring on 90 additional serum samples ( n = 30 per group), 11 discriminatory proteins were obtained using supervised multivariate statistical analysis. We further evaluated 3 candidates using ELISA and immunohistochemistry (IHC). S100A9, thioredoxin (TRX), and cadherin-related family member 2 (CDHR2) were significantly different between CCA and normal, and CCA and PDF groups when measured in an additional 247 serum samples ( P < 0.0001). By IHC, TRX and CDHR2 were detected in the cytoplasm and nucleus of CCA and inflammatory cells. S100A9 was detected in the infiltrating tumor stroma immune cells. Proteomics discovery and qualification in depleted sera revealed promising biomarker candidates for CCA diagnosis.

Cholangiocarcinoma (CCA) is a primary malignant tumor of the epithelial lining of biliary track associated with endemic Opisthorchis viverrini (Ov) infection in northeastern Thailand. Ov-associated periductal fibrosis (PDF) is the precancerous lesion for CCA, and can be detected by ultrasonography (US) to facilitate early detection. However, US cannot be used to distinguish PDF from cancer. Therefore, the objective of this study was to discover and qualify potential urine biomarkers for CCA detection in at-risk population. Biomarker discovery was conducted on pooled urine samples, 42 patients per group, with PDF or normal bile duct confirmed by ultrasound. After depletion of high abundance proteins, 338 urinary proteins were identified from the 3 samples (normal-US, PDF-US, CCA). Based on fold change and literature review, 70 candidate proteins were selected for qualification by multiple reaction monitoring mass spectrometry (MRM-MS) in 90 individual urine samples, 30 per group. An orthogonal signal correction projection to latent structures discriminant analysis (O-PLS-DA) multivariate model constructed from the 70 candidate biomarkers significantly discriminated CCA from normal and PDF groups (P = 0.003). As an independent validation, the expression of 3 candidate proteins was confirmed by immunohistochemistry in CCA tissues: Lysosome associated membrane glycoprotein 1 (LAMP1), lysosome associated membrane glycoprotein 2 (LAMP2) and cadherin-related family member 2 (CDHR2). Further evaluation of these candidate biomarkers in a larger cohort is needed to support their applicability in a clinical setting for screening and monitoring early CCA and for CCA surveillance., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To assess associations between periductal fibrosis (PDF) and bile duct dilatation (BDD) in ultrasonography (US) screening of population at risk of cholangiocarcinoma (CCA) due to residence in an endemic area for Opisthorchis viverrini. CCA survival rates are low, and early identification of risk factors is essential. BDD is one symptom that can identify patients at risk of CCA. Detection of PDF by US can also identify at-risk patients, at an earlier stage of CCA development. Identification of association between PDF and BDD will inform screening practices for CCA risk, by increasing the viability of PDF screening for CCA risk., Setting: Nine tertiary care hospitals in Northeast Thailand., Design: Cross-sectional study., Participants: Study subjects in the Cholangiocarcinoma Screening and Care Program (CASCAP) in Northeast Thailand. CASCAP inclusion criteria are all residents of Northeast Thailand aged ≥40 years. Participants are recruited through CCA screening centres and through primary healthcare units. So far, 394 026 have been enrolled., Methods: PDF and BDD were identified through US. PDF was categorised into three groups, PDF1, 2 and 3, depending on their high echo locality in the peripheral, segmental and main bile duct, respectively. Associations between PDF and BDD were determined by adjusted OR and 95% CI using multiple logistic regression., Results: BDD was found in 6.6% of PDF3, 1.7% of PDF2 and 1.4% of PDF1 cases. Among PDF cases, especially in PDF3, BDD was found in men more than in women (8.9% and 4.6%, respectively). Compared with non-PDF, the association between PDF3 and BDD was highly significant (adjusted OR=5.74, 95% CI 4.57 to 7.21, p<0.001)., Conclusions: Our findings reveal that there is a relationship between PDF and BDD, which is associated with CCA. Therefore, PDF can also be an indicator for suspected CCA diagnosis through US., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Cholangiocarcinoma (CCA) is the primary tumor found in the bile duct and is associated with a high incidence of lymph node (LN) metastases and poor outcomes. The presence of metastatic lymph nodes, when shown by imaging, can influence patient treatment and prognosis. DWI is a promising, non-invasive imaging technique for differentiating between benign and malignant LNs. Many studies have shown that LN metastases have a lower apparent diffusion coefficient (ADC) value when compared to benign nodes., Objective: To evaluate the performance of ADC values as a basis for diagnosis of LN metastasis in cholangiocarcinoma patients., Materials and Methods: This was a retrospective imaging study that evaluated histopathologically proven intraabdominal LNs in cholangiocarcinoma patients who underwent a 1.5T abdomen MRI with DWI between January 2012 and July 2016. The ADC values and short-axis diameters of the LNs were measured and compared using student's t test. Receiver operating characteristic (ROC) curves were used to determine the threshold., Results: A total of 120 lymph nodes-85 benign and 35 metastatic-were included. The mean short-axis diameter of the benign LNs (8.34 mm) was significantly lesser than that of the malignant LNs (9.56 mm). Receiver operating characteristic curve analysis using a size criterion of 1 cm yielded a value of 0.63. A diagnostic size criterion of 1 cm for the short axis was applied and yielded an accuracy of 66%, sensitivity/specificity of 41%/75%, and positive/negative predictive value of 34%/80%. The mean ADC values of metastatic (1.31 × 10 -3  mm 2 /s) LNs were not significantly different from those of non-metastatic LNs (1.29 × 10 -3  mm 2 /s)., Conclusion: There was no difference in terms of ADC value between benign lymph nodes and those with metastatic cholangiocarcinoma. Isolated measurement of the ADC value does not contribute to a diagnosis of lymph node metastasis.

Inflammation of the hepatobiliary system in chronic opisthorchiasis is associated with an elevated level of urinary 8-oxo-7,8 dihydro-2'deoxyguanosine (8-oxodG) during active as well as past exposure to Opisthorchis viverrini infection. In this study, we evaluated the short-term effect of praziquantel treatment on hepatobiliary disease (HBD) using urinary 8-oxodG as an inflammatory marker in a cohort of residents in endemic areas of opisthorchiasis in Khon Kaen, Thailand. The HBD status in terms of periductal fibrosis (PDF) was determined by abdominal ultrasonography and O. viverrini infection was monitored at baseline and 2-4 weeks after curative treatment by praziquantel. Analysis of O. viverrini-infected participants who were PDF-ve revealed that there was a significant reduction of urinary 8-oxodG after treatment compared with the baseline levels (p <  0.001). By contrast, in PDF+ve individuals, the levels of urinary 8-oxodG were similar between baseline and those post-treatment. Although confirmation by using a larger sample size is needed, the positive association between HBD and urinary 8-oxodG level after worm clearance suggests that chronic hepatobiliary inflammation is neither affected nor interrupted by short-term praziquantel treatment. Individuals with persistent PDF at pre- and post-treatment who have a high risk of cholangiocarcinoma, could be identified within 2-4 weeks after parasite removal by drug treatment. Thus, urinary 8-oxodG is a useful biomarker for predicting persistent PDF in individuals with a recent drug treatment history who require further clinical investigation, management and treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Previous studies demonstrated that urinary 8-oxodG is a predictive biomarker for Opisthorchis viverrini (OV)-associated hepatobiliary disease (HBD) and cholangiocarcinoma (CCA). This study examined the effects of praziquantel treatment on the profile of urinary 8-oxodG in relation to HBD status. Infection with OV, levels of urinary 8-oxodG, and HBD status in terms of periductal fibrosis (PDF) assessed by abdominal ultrasonography (US) were monitored and compared in cohorts of participants in Khon Kaen, Thailand, before and 1 year after praziquantel treatment. Urinary 8-oxodG levels significantly decreased after treatment compared with the baseline level in OV-infected participants who had no HBD (PDF negative; PDF-ve) ( N = 14). Levels of 8-oxodG were unchanged after treatment in OV-infected subjects (OV+ve) who had positive PDF ( N = 52). Within the positive PDF (PDF+ve) group who became PDF-ve after treatment, there was no significant change in 8-oxodG levels between pre-and posttreatment (reversible PDF = 65.3%). In those who had persistent PDF+ve at both ultrasound sampling points, there was no significant difference in urinary 8-oxodG levels between pre- and posttreatment (persistent PDF = 34.6%). Based on a logistic regression model and receiver operation curve analysis, the increase of 8-oxodG levels was found to be associated with increasing risk of PDF. Measurement of urinary 8-oxodG and US increased the likelihood of discovering persistent PDF, which is a predictable condition for the patients at risk of OV-associated CCA. To identify high-risk individuals for CCA, it is useful to perform US in combination with urinary 8-oxodG measurement.

Similar to bile duct cancer or cholangiocarcinoma (CCA) in the western world, opisthorchiasis-associated CCA in Southeast Asia is an aggressive cancer with high mortality rates. It is known to cause a significant health burden in the opisthorchiasis region in Thailand and possibly throughout mainland Southeast. To reduce this health burden, a comprehensive prevention and control program for opisthorchiasis, as well as CCA, is required. In this review, our aim is to provide a brief update of the current situation regarding the natural history of opisthorchiasis and health burden of CCA in Southeast Asia. A comprehensive approach to tackling these issues being implemented in Thailand under the "Cholangiocarcinoma Screening and Care Program" is described. This comprehensive program consists of a three stage prevention and patient care program. The primary prevention component involves opisthorchiasis screening using a new and sensitive urine assay. The secondary prevention component involves screening for CCA and periductal fibrosis, with suspected CCA patients following the protocol for confirmation and appropriate treatment. Due to the eco-epidemiology of opisthorchiasis-induced CCA, the anticipated impacts and outcomes of the program include short-, medium-, and the long-term goals for the reduction of CCA incidence. To achieve long-term sustainable impacts, concerted efforts to raise social awareness and participating action by general public, non-government organizations, and government agencies are necessary. The strategic plans developed for this program can be expanded for use in other endemic areas as well as being a model for use in other chronic diseases.

The northeast of Thailand, which is the poorest region of the country, has the highest incidence of cholangiocarcinoma (CCA) worldwide. This is associated with infection with the liver fluke Opisthorchis viverrini. Although an estimated 20,000 people die every year of this disease, the socioeconomic impact of this mortality on the victims' family and the community in which he or she lived remains unknown. Here, we provide background information on the socioeconomic groups most effected by CCA and provide a qualitative estimate of the likely financial burden on the family and community. Most victims of CCA are small-scale farmers. Mortality occurs most commonly in males between the ages of 40 and 65, having either children or grandchildren to support. Costs can be divided between premortality with the family paying for transport and accommodation to the hospital, as well as costs not covered by the Thai Universal Health Coverage scheme. The main costs, however, are likely to be postmortem with loss of income and potentially the loss of a major contributor to farm work. What is urgently required is a quantitative estimate of the costs of CCA and long-term studies of the families and communities affected to determine where and how the burden of CCA falls., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Treatment planning especially liver resection in cholangiocarcinoma (CCA) depends on the extension of tumor and lymph node metastasis which is included as a key criterion for operability. Magnetic resonance imaging (MRI) offers a rapid and powerful tool for the detection of lymph node metastasis (LNM) and in the current manuscript is assessed as a critical tool in the preoperative protocol for liver resection for treatment of CCA. However, the accuracy of MRI to detect LNM from CCA had yet to be comprehensively evaluated., Methods: The accuracy of MRI to detect LNM was assessed in a cohort of individuals with CCA from the Cholangiocarcinoma Screening and Care Program (CASCAP), a screening program designed to reduce CCA in Northeastern Thailand by community-based ultrasound (US) for CCA. CCA-positive individuals are referred to one of the nine tertiary centers in the study to undergo a preoperative protocol that included enhanced imaging by MRI. Additionally, these individuals also underwent lymph node biopsies for histological confirmation of LNM (the "gold standard") to determine the accuracy of the MRI results., Results: MRI accurately detected the presence or absence of LNM in only 29 out of the 51 CCA cases (56.9%, 95% CI 42.2-70.7), resulting in a sensitivity of 57.1% (95% CI 34.0-78.2) and specificity of 56.7% (95% CI 37.4-74.5), with positive and negative predictive values of 48.0% (95% CI 27.8-68.7) and 65.4% (95% CI 44.3-82.8), respectively. The positive likelihood ratio was 1.32 (95% CI 0.76-2.29), and the negative likelihood ratio was 0.76 (95% CI 0.42-1.36)., Conclusions: MRI showed limited sensitivity and a poor positive predictive value for the diagnosis of LNM for CCA, which is of particular concern in this resource-limited setting, where simpler detection methods could be utilized that are more cost-effective in this region of Thailand. Therefore, the inclusion of MRI, a costly imaging method, should be reconsidered as part of protocol for treatment planning of CCA, given the number of false positives, especially as it is critical in determining the operability for CCA subjects.

Background. Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. A large number of studies have strongly described larger proportions of men being afflicted with NAFLD than women; however, recent studies investigating the role of gender and NAFLD have exposed the contrary. Methods. This cross-sectional study utilized data from the baseline survey of an ongoing cohort study called the Cholangiocarcinoma Screening and Care Program (CASCAP), conducted in the northeastern region of Thailand between March 2013 and September 2015. Information regarding socio-demographic, including gender, was collected using a standardized self-administered questionnaire. NAFLD was diagnosed with ultrasonography by board-certified radiologists. A binomial regression was used for estimating the prevalence differences, odds ratios (OR) and the 95% confidence intervals (CI) of NAFLD between men and women. Results. A total of 34,709 participants (27,073 females and 7,636 males) were recruited. The prevalence of NAFLD in women was 22.9% (95% CI: 22.5 to 23.5), whereas it was only 18.3% (95% CI: 17.4 to 19.2) in men. After adjusting for age and presence of diabetes mellitus and other underlying diseases, the prevalence was significantly higher in women, with adjusted prevalence difference of 4.2% (95% CI: 3.2 to 5.2) and adjusted OR of 1.3 (95% CI: 1.2 to 1.4). Women had a higher prevalence of NAFLD than men in all age groups and the largest difference was found in those aged 56-60 years (prevalence = 27.4% versus 21.2%; adjusted prevalence difference = 9.4%; 95% CI: 7.9 to 10.9; adjusted OR = 1.8; 95% CI: 1.8 to 2.0). Conclusion. NAFLD is more likely to affect women more than men, in particular, among the population 56-60 years of age, which is the post-menopausal transitional period. Therefore, post-menopausal women should be the target for interventions or further investigation for NAFLD., Competing Interests: Competing interests: No competing interests were disclosed.

Although cholangiocarcinoma (CCA) is usually a rare cancer, in northeast Thailand it kills 20 000 or more people every year. The prognosis is very poor owing to late stage diagnosis, with palliative treatment often representing the only option. In this area of predominantly rural Thailand, CCA is associated with infection with the liver fluke, Opisthorchis viverrini , which is classified as a group 1 carcinogen. Up to 6 million Thais are infected with this fluke. The Cholangiocarcinoma Screening and Care Program (CASCAP) was initiated in 2014 with the aim of detecting early stage CCA, allowing curative surgery, by using ultrasound (US) screening of prospectively 500 000 at risk individuals. In order to assess the massive number of radiological images, a teleconsultation system was set-up. This allows US images to be sent to a dedicated server where they can be viewed by an expert radiologist who then provides a provisional diagnosis, recommending more advanced diagnostic techniques (CT and MRI) for suspected cases. To date, 250 000 people have been screened, and 2000 cases of CCA diagnosed. This innovative information transfer procedure will also be made available to Laos, Cambodia and Vietnam, where O. viverrini infection is also common., Competing Interests: Competing interests: None declared.

Opisthorchis viverrini infection induces chronic inflammation in the bile ducts, leading to periductal fibrosis (PDF), which possibly associates to cholangiocarcinoma (CCA). Patients with CCA have a poor prognosis, which is linked to asymptomatic disease and late diagnosis. Hence, detecting early stage CCA is essential. Secretory miRNAs have been promoted as biomarkers for pathological changes associated with parasitic infections, fibrosis and/or cancer. We aimed to determine levels of miR-192 and miR-21 in the urine of O. viverrini infected, periductal fibrosis (PDF) and CCA groups using qRT-PCR. We found that miR-192 was significantly higher in O. viverrini infected, PDF and also CCA groups (p<0.05) than in healthy controls. By utilizing the Receiver Operation Characteristics (ROC) analysis, miR-192 differentiated patients with opisthorchiasis (the area under the curve; AUC=0.766), PDF subjects (AUC=0.781) and CCA patients (AUC=0.682) from healthy controls. MiR-21 was significantly higher in PDF and CCA groups (p<0.05) than in healthy controls. MiR-21 discriminated PDF subjects (AUC=0.735) and CCA patients (AUC=0.682) from healthy controls. Combined levels of these two miRNAs revealed an increased AUC of 0.812 for separating opisthorchiasis, AUC of 0.815 in discriminating PDF subjects, and AUC of 0.849 in differentiating CCA from healthy controls. Odds ratios (OR) indicated high levels of miR-192/miR-21 as risk predictors for opisthorchiasis, PDF and CCA. Levels of these miRNAs declined significantly for patients following praziquantel treatment. In conclusion, urinary miR-192/miR-21 have potential as risk indicators for opisthorchiasis and PDF-associated CCA in the endemic region., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Cholangiocarcinoma is relatively rare worldwide. Most previous reports collected only patients with pathological diagnosis. In fact, however, many patients coming to hospital are diagnosed by clinical suspicion with radiologic imaging and receive treatment without histological confirmation. Real survival data and outcome of each treatment, especially for patients that do not have histologic confirmation, are lacking. In this study, therefore, we aimed to analyze the survival rates of CCA patients and the proportions of patients receiving different treatments., Materials and Methods: A total of 270 patients clinically suspected of CCA and visiting Srinagarind Hospital in May-July 2010, were prospectively followed until December 2014. After checking their clinical records, 163 of 270 patients were finally diagnosed as having CCA, and the data of this group were analyzed for survival rate and received treatments., Results: Of the 163 patients, 96 (58.9%) had intrahepatic, 56 (34.4%) had perihilar and 11 (6.7%) had distal CCA. The majority [107 (65.6%, 95%CI, 57.8-73.0)] received only supportive care. Overall median survival was 4 months (95%CI, 3.3-4.7), and 2-years survival was only 8.1% (95%CI,4.5-12.9). However, the 4 year survival of the R0 resection group was 100%., Conclusions: The present results show that the prognosis of CCA is very poor in North-east Thailand. Most CCA patients receive only treatment to alleviate symptoms due to their advanced stage of disease. Complete surgical resection at the early stage is the only treatment that significantly improves patient survival.

Background: The population in northeast Thailand continues to present with hepatobiliary abnormalities, particularly periductal fibrosis (PDF) which is the result of chronic infection with liver fluke (Opisthorchis viverini; OV) and may lead to the development of cholangiocarcinoma (CCA). Although the prevalence of OV infection has been decreased due to a liver fluke control program over decades, the prevalence of PDF remains high. This study aimed to investigate demographic factors associated with PDF risk based on ultrasonography (US) screening., Materials and Methods: This cross-sectional study is part of the Cholangiocarcinoma Screening and Care Program (CASCAP), a prospective cohort study. Multiple logistic regression was used for data analysis., Results: In 55,246 subjects, the overall prevalence of PDF was 33.0% (95%CI: 32.6 - 33.4). Males (33.9 %) were at higher risk for developing PDF than females (32.2 %) (ORcrude = 0.93; 95%CI: 0.89 - 0.96; p-value < 0.001). Factors associated with an increased PDF risk, in addition to OV infection, included old age (≥ 70 years) (ORadj =1.28, 95% CI: 1.14 - 1.44, <0.001) and hepatitis B infection (ORadj = 1.31, 95% CI: 1.11 - 1.55, p = 0.001). In contrast, number of praziquantel treatments (> 2 times) (ORadj = 0.54, 95% CI: 0.47 - 0.63, <0.001) and diabetes mellitus (ORadj =0.57, 95% CI: 0.49 - 0.65, <0.001) were significantly associated with a decreased PDF risk., Conclusions: Future US screening should closely examine older people and hepatitis B subjects for the purpose of PDF surveillance among high risk groups for CCA. However, the results of inverse associations require further investigation in order to confirm our findings.

Background: Cholangiocarcinoma (CCA) is an extremely aggressive cancer that is usually fatal. Although globally morbidity and mortality are increasing, knowledge of the disease remains limited. The Mekong region of Southeast Asia, and particularly the northeast of Thailand, has by far the highest incidence of CCA worldwide with 135.4 per 100,000 among males and 43.0 per 100,000 among females being reported in Khon Kaen Province. Most patients are first seen during late stage disease with 5-year survival being less than 10%. Starting in 1984, control and prevention strategies have been focused on health education. Although early detection can substantially increase 5-year survival, there are currently no strategies to increase early diagnosis., Methods/design: The Cholangiocarcinoma Screening and Care Program (CASCAP) is a prospective cohort study comprising two cohorts- the screening and the patient cohorts. For the screening cohort, ultrasound examination will be carried out regularly at least annually to determine whether there is current bile duct and/or liver pathology so that the optimal screening program for early diagnosis can be established. This cohort is expected to include at least 150,000 individuals coming from high-risk areas for CCA. For the patient cohort, it is estimated that about 25,000 CCA patients will be included during the 5-year recruitment period. All CCA patients will be treated according to routine clinical care and followed so that effective surgical treatment can be formulated. This cohort is indeed a conventional cancer registry. Thus, CASCAP is an ongoing project in which the number of participants changes dynamically., Discussions: This is the first project on CCA that involves screening the at risk population at the community level. At the time of preparing this report, a total of 85,927 individuals have been enrolled in the screening cohort, 55.0% of whom have already undergone ultrasound screening, and 2661 CCA cases have been enrolled in the patient cohort. Among the participants of the screening, whose mean age was 53.8±9.8 years, 55.6% were female, 77.5% attained primary school as the highest level of education, 79.9% were farmers, 29.9%, reported having relatives with CCA, 89.1% had eaten uncooked fish, and 42.2% of those who had been tested for liver fluke were found to be infected.

Fatty liver disease (FLD) can be a precondition for other liver pathology including cholangiocarcinoma (CCA). Diabetes mellitus (DM) has been suggested in some studies to be a risk factor for FLD as well as cancers, including cholangiocellular carcinoma; however, there are currently very few studies on FLD in DM subjects, although the rate of FLD continues to increase annually. To determine the association between DM and FLD ultrasonographic data were analyzed from the Cholangiocarcinoma Screening and Care Program (CASCAP), in northeast Thailand. DM was reported by the subjects based on the CASCAP health questionnaire. Factors that were associated with FLD were determined by prevalence, odds ratio (ORs) and its 95% confidence intervals (CIs) using multiple logistic regression. There were 45,263 subjects with a mean age of 53.46 (±9.25) years. FLD was found in 36.3% of DM subjects but only in 20.7% of non-DM subjects. The association between DM and FLD was adjusted for all other factors including gender, age, education level, relatives diagnosed with CCA, smoking, alcohol consumption, and hepatitis B and C. The risk of DM in subjects having FLD was highly significant compared with the non-DM subjects (OR 2.13; 95%CI: 1.92 to 2.35; p-value < 0.001). Thus DM is significantly associated with FLD which in turn may facilitate the development of several diseases including CCA. DM should be taken into consideration in future ultrasonic investigations of FLD and CCA.

Background: This study aimed to investigate the miR-192 levels in patients' sera of liver fluke-associated cholangiocarcinoma (CCA) for a prospective prognostic indicator., Methods: MicroRNA polymerase chain reaction (PCR) array was performed using pooled serum samples from 11 CCA patients and nine healthy subjects. Selected miRNAs were verified for the differential levels in both sera and tumor tissues (of patients and Opisthorchis viverrini (Ov)-induced CCA model) using TaqMan miRNA expression assay., Results: Our results demonstrated that miR-192 was significantly higher in the serum of CCA patients than that in healthy subjects giving a sensitivity of 74% and specificity of 72% (area under the curve [AUC] = 0.803; 95% confidence interval [CI], 0.708-0.897, P < 0.0001). Serum miR-192 examined in Ov infected subjects and subjects with periductal fibrosis were increased but not statistically significantly when compared with healthy subjects. High levels of serum miR-192 were significantly correlated with lymph node metastasis (P = 0.047) and shorter survival compared with individuals with low levels of serum miR-192 (hazard ratio [HR] 2.076, 95% CI 1.004-4.291, P = 0.049). We also found that the expression levels of miR-192 appeared to be elevated in both CCA tissues of patients and in Ov-induced CCA tissues of a hamster model., Conclusions: This finding indicates that elevated levels of miR-192 may be involved in CCA genesis and have a potential utility as a noninvasive prognostic indicator for CCA patients., (© 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Cholangiocarcinoma (CCA) has no specific clinical signs and symptoms and non-specific bio- and tumor-markers in the early disease stage. Usually patients present to tertiary care with advanced disease stage. In order to detect early cases of CCA that may present as a mass, dilatation of intrahepatic duct or combination, ultrasonography is accepted as a powerful imaging tool. A smaller mass or bile duct segmental dilatation requires further imaging for characterization, including computerized tomography (CT) or magnetic resonance imaging (MRI). We examined whether liver echo pattern was correlated with high risk for CCA in an endemic area of Opisthorchis viverrini (Ov). Ov infestation caused chronic inflammation of the biliary tree by periductal fibrosis (PDF), which may subsequently lead to CCA development. In our study, a World Health Organization classification of pattern of increased periportal echo (IPE) for schistosomiasis was applied. Two CCA patients gave consent for operation. Histopathological diagnosis showed both had cholangiocarcinoma with periductal fibrosis of the non-tumorous area of the liver. Ultrasonography was used to compare the non-tumorous area with parenchymal echo pattern and was shown to have an early CCA detection role and a surveillance role in an endemic area of Ov by detection of PDF., (© 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Hepatocellular carcinoma (HCC) is associated with high mortality. Patients with hepatitis B or C viral cirrhosis have an increased risk of developing HCC. Ultrasound is the most widely used screening method, and is recommended by many guidelines., Objective: To study the sonographic findings ofHCC detected in ultrasound surveillance of cirrhotic patients., Material and Method: Retrospective assessment of ultrasoundfindings of all nodules that were diagnosed HCC by either dynamic imaging (CTor MRI) or biopsy between October 2008 and July 2011. Nodules were classified based on echogenicity and other sonographic characteristics., Results: Of 92 nodules, 42 (45.7%) were hyperechoic, 29 (31.5%) hypoechoic, 20 (21.7%) heterogeneous echoic and 1 (1.1%) isoechoic. Heteroechoic nodules were more common among nodules over 3.0 cm (p = 0.0037) while hypoechoic nodules tended to be the smaller ones. About half (48/92) of the nodules had a hypoechoic halo and occurred significantly more commonly among hyperechoic and heteroechoic nodules (p< 0. 001). Posterior enhancement was found in 54 nodules (58. 7%0), also more common in nodules >3.0 cm (p = 018). Lateral shadowing occurred in 40 nodules (43.5%)., Conclusion: The sonographic findings of HCC nodules in the present studies varied, but the prevalence of hyperechoic nodules was higher than in most of other studies. The authors emphasize the necessity of performing dynamic imaging for any nodule detected in a cirrhotic liver in order to exclude their neoplastic nature, no matter what it may look like.

Antitumor activity (growth suppression) of vitamin D has been demonstrated using cholangiocarcinoma (CCA) cell lines, CCA cell-grafted animal models, and human CCA tissue cultures. The present study aimed to determine the toxicity and tolerability of intermittent-high dose calcitriol in advanced inoperable intrahepatic CCA patients and to evaluate the therapeutic efficacy of combinations of calcitriol and 5-fluorouracil-based chemotherapeutic drugs. The patients were divided into 3 groups: the first (n=2) received intermittent-high dose oral calcitriol 12 μg/day for 3 days, i.e. Monday-Wednesday, per week up to 3 months. The treatment did not cause any serious adverse events, except hypercalcemia grade I, once in 72 administrations. The second group (n=3) received chemotherapeutic drugs (5-fluorouracil, Mitomycin C and Leucovorin) for 3 cycles, one patient showing a partial response. The third group (n=4) received high dose calcitriol in combination with chemotherapeutic-drugs. All 4 patients encountered serious adverse events and two of them were withdrawn after the first drug cycle. This pilot study suggests that, although high dose-intermittent calcitriol appeared to be safe and tolerated well in advanced intrahepatic CCA patients, co-administration with 5-fluorouracil-based chemotherapeutic drugs caused unexpected potentiation of their toxicity. Adjustment of the doses of both drugs is required to avoid such toxicity and to optimize therapeutic efficacy of anticancer drugs when they were combined with high dose-intermittent calcitriol.

Objective: To compare the CT findings of adenocarcinoma and malignant lymphoma of the stomach., Material and Method: The authors retrospectively reviewed the computed tomographic images of 21 patients who received a definite pathologic diagnosis of adenocarcinoma or malignant lymphoma of the stomach. The images were taken at Srinagarind Hospital between January 2006 and February 2009. Seventeen patients with gastric adenocarcinoma and four with malignant gastric lymphoma were included in the present study. The pattern of involvement, the location of lesion, the perigastric fat plane, the perigastric lymphadenopathy and the extension of disease on CT images were evaluated and analyzed by Chi-square and Fisher exact tests., Results: There was a statistically significant difference between gastric adenocarcinoma and malignant gastric lymphoma in the pattern of involvement of disease (p = 0.010), the perigastric fat plane (p = 0.002) and the location of disease (p = 0.008). By contrast, there was no respective statistically significant difference in the perigastric lymphadenopathy (p = 0.950) and the extension of disease (p = 0.175) in between gastric adenocarcinoma and malignant gastric lymphoma., Conclusion: The CT findings helpful for differentiating gastric adenocarcinoma from malignant gastric lymphoma are the pattern of involvement, the perigastric fat plane, and the location of lesion. Localized involvement of the lesion, abnormal perigastric fat plane and location involving one region of the stomach tend to indicate gastric adenocarcinoma; while diffused involvement of the lesion, preserved perigastric fat plane and location involving more than one region of the stomach tend to indicate malignant gastric lymphoma.

Background: There are various computed tomographic appearances of liver metastases from colorectal cancer, but there is little data in Thailand., Material and Method: This was a retrospective, descriptive study of the CT appearances of 21 patients diagnosed with liver metastasis from colorectal cancer in Srinagarind Hospital, Khon Kaen, between January 2003 and December 2007. All of the patients were examined in the portovenous phases., Results: Rim-enhancement was seen in 20 patients (95.2%). Irregular rim-enhancement was seen in 19 patients (90.5%) and smooth rim-enhancement in one (4.8%). Thin rim was seen in 16 patients (76.2%) and thick rim in four (19%). Internal heterogeneous enhancement was seen in 15 patients (71.4%). Irregular, thin rim-enhancement with internal heterogeneous enhancement was the most common combination seen in 12 patients (57.1%)., Conclusion: An enhancing rim could be seen in 95.2% of patients. Internal heterogeneous enhancement was shown in 71.4% of patients. Familiarity with the various CT appearances may help to facilitate the diagnosis of colorectal liver metastases.

Objective: To compare the computerized tomographic (CT) findings of hepatic fascioliasis (HF) vs. melioidosis-caused liver (ML) abscesses., Material and Method: CT images of 15 patients with hepatic fascioliasis (HF) and 16 patients with melioidosis-caused liver (ML) abscesses were retrospectively reviewed. The authors evaluated and compared HF and ML abscesses (by chi2 and Fisher exact tests) vis-a-vis their location of liver involvement, size, shape, number margins, enhancement patterns, subcapsular lesions, internal architecture, dilatation of intrahepatic bile duct and combination with splenic abscesses., Results: Fourteen HF patients had only liver abscesses and 1 had combined liver and splenic abscesses. Four ML patients had liver abscesses alone while 12 had combined liver and splenic abscesses (p = 0.000). Eight of the 15 HF (53.3%) and 2 of the 16 ML (12.5%) patients had subcapsular lesions (p = 0.019). The liver abscesses were round or oval with linear tracts in 8 of the 15 HF (53.3%) and none of the ML patients (p = 0.001). Between the respective HF and ML patients, there was a significant difference in those with round shaped in ML (p = 0.008), multiple and conglomerately distributed in HF (p = 0.050), multiple and discretely distributed in ML (p = 0.001) no (or minimal) peripheral contrast enhancement in HF (p = 0.011) and moderate or mark peripheral enhancement in ML (p = 0.011)., Conclusion: The CT findings of liver abscesses that helped to differentiate hepatic fascioliasis from melioidosis liver abscesses were: their number shape, enhancement pattern, presence of subcapsular lesion (s) and co-occurrence with splenic abscesses. The diagnosis of hepatic fascioliasis by CT is suggested when the following characteristics were seen: (1) multiple, small round or oval (with linear tracts) conglomerates presenting as hypodense lesions; (2) no (or minimal) peripheral contrast enhancement; (3) subcapsular lesions; or (4) less frequent co-occurrence with splenic abscesses.

Objective: To compare the CT findings of the intraductal and periductal cholangiocarcinoma (CCA) in Srinagarind Hospital., Material and Method: The authors retrospectively reviewed the abdominal CT images (taken between January 2004 and December 2005) of 60 patients with pathologicalproof of CCA. There were 34 and 26 cases of the intraductal and periductal CCA, respectively. The bile duct dilatation, size and location of the intraductal and infiltrative extraductal masses, ductal wall enhancement and other associated findings (i.e., biliary stones, ascites, intra-abdominal lymphadenopathy and distant metastases) were compared and analyzed using the chi2 and Fisher exact tests., Results: All cases of the intraductal and periductal CCA showed bile duct dilatation. The intraductal mass was seen in all cases of the intraductal CCA but none in the periductal CCA (p = 0.00). All intraductal mass sizes were >1 cm. Most (77%, n = 20/26) cases of the periductal CCA had an infiltrative extraductal mass, whereas none were found in the intraductal CCA (p = 0.00). Ductal wall enhancement was found in 73% (n = 19/26) of the periductal CCA and 26% (n = 9/34) of the intraductal CCA cases (p = 0.01). Only one case in each group presented with biliary stones. Half (50%, n = 13/26) and 12% (n = 3/26) of the periductal CCA cases demonstrated with intra-abdominal lymphadenopathy and ascites, respectively, vs. none in the intraductal CCA (p = 0.00 and 0.07, respectively). No distant metastasis was found in either group., Conclusion: The CT findings that helped to diferentiate the intraductal from periductal CCA include: the intraductal mass, an infiltrative extraductal mass, ductal wall enhancement and other associated findings such as intra-abdominal lymphadenopathy. Features of the intraductal CCA included the intraductal mass without intra-abdominal lymphadenopathy and ductal wall enhancement about 26% (9/34 cases).

Objective: To compare the CT findings of liver and splenic abscesses in melioidosis (ML) with non-melioidosis (NML)., Material and Method: CT (computed tomography) images of 47 patients with liver and splenic abscesses were retrospectively reviewed. The 28 patients with ML abscesses and 19 with NML abscesses were recruited into the present study. The sizes, shapes, distributions, margins, enhancement patterns and internal architectures of abscesses on CT images were evaluated and analyzed by Chi-square and Fisher exact tests., Results: Seven and 6 ML patients had liver and splenic abscesses alone respectively, and 15 patients had combined liver and splenic abscesses. All NML patients had only liver abscesses. For liver abscesses, there were 3 ML and 13 NML patients with abscess size > or = 3 cm. Eleven ML and no NML patients had abscesses < 3 cm (p = 0.00). The abscesses were multiple and discretely distributed in all 11 ML patients, but none in NML patients (p = 0.002). Seven ML and 13 NML patients had moderate to marked peripheral enhancement (95% CI: -0.7, -0.01). All splenic abscesses (21 patients) found that B. pseudomallei was the causative organism. They were mostly smaller than 3 cm in size (85.71%), multiple (95.24%), and had no or minimal enhancement (85.71%)., Conclusion: The CT findings of liver abscesses that can help to differentiate ML from NML include sizes, distributions, and enhancement patterns. The features of ML splenic abscesses in the present study were small, multiple, with no or minimal contrast enhancement.

Objective: To describe anatomical distribution and CT findings of gastrointestinal stromal tumors in Srinagarind Hospital., Material and Method: The abdominal CT images of 16 patients (12 men, 4 women: mean age 49 +/- 17SD) with pathologically proven GISTs during 1998-2005 were retrospectively reviewed. The tumor sites, sizes, borders, growth patterns, patterns of enhancement, and sign of malignancy were evaluated. The findings of benign and malignant GISTs were compared., Results: Among sixteen patients, the most common location of GISTs was stomach (56.25%). The others were small bowel (43.75%), and tumor size larger than 5 cm. The present study found that the smooth and mixed smooth and irregular surface lesions are equal in number (50%). The growth was extraluminal in 56.25%. Almost all tumors had inhomogeneous density (n = 15). Intratumoral gas (43.75%), fluid (37.5%), and calcification (50.00%), were present in the tumors. All cases showed inhomogeneous contrast enhancement. The CT signs of malignancy found were invasion of the adjacent organ(s) (62.5%), lymphadenopathy (25%), liver metastasis/nodule (18.75%), ascites (6.25%), perilesional fat plane stranding (93.75%), and pleural effusion (6.25%)., Conclusion: The most common site of GISTs is the stomach. The typical tumors appear as inhomogeneous enhancing inhomogeneous extraluminal mass with either well-defined or irregular border. The CT findings cannot be used as a single tool for differentiating the benign from malignant GISTs.

Objective: To assess the accuracy of spiral CT scan in the preoperative staging of gastric carcinoma by comparing it with surgical/pathological staging., Material and Method: Twenty-eight patients with gastric carcinoma who underwent both preoperative CT scan and surgery were retrospectively studied for TNM classification. All CT scans were reviewed for tumor location, gastric wall thickness, tumor extension, N1 and N2 nodal involvement, and metastases to the liver, peritoneum and lung., Results: Spiral CT staging was correct in 20 of 28 patients (71.4%). The preoperative CT scan had 96.1% sensitivity, 100% specificity and 96.4% accuracy for evaluating serosal invasion. The sensitivity, specificity and accuracy for assessing pathologic lymph node involvement were 73.1, 50.0 and 84.2 percent, respectively. In the present study, peritoneal metastasis could not be identified by CT but CT had 100% sensitivity for evaluating hepatic metastases., Conclusion: Spiral CT is a useful modality for preoperative staging of gastric carcinoma with high accuracy for evaluating serosal invasion and hepatic metastases.

The authors report a case of systemic lupus erythematosus with posterior leukoencephalopathy who presented with headache, tonic-clonic seizure, loss of consciousness and bilateral loss of vision, after taking azathioprine for three weeks. The patient had hypertension with normal eye grounds. The brain CT showed a hypodensity lesion at both bilateral occipital lobes, mainly in the white matter The symptoms and follow-up MRI were improved after the control of hypertension and discontinuation of azathioprine.

In Thailand, liver cancer is the most common malignancy in males and the third most common among females. In the Northeast region, cholangiocarcinoma (CHCA) is the prevalent type, with Opisthorchis viverrini (OV), an endemic liver fluke, being considered the cause. We evaluated the role of ultrasound (U/S) for cholangiocarcinoma screening as part of a larger cohort to characterize the linkage between liver fluke infestation and CHCA in Khon Kaen (Northeast Thailand). Most people (77%) had normal U/S findings while only 0.5% had suspected CHCA; thus, U/S should be used primarily for those with the highest risk, presenting symptoms and/or being OV positive.

Objectives: To evaluate the role of CT scan in preoperative staging of colorectal carcinoma by comparing it with the surgical-pathologic staging and pathologic findings., Material and Method: The CT scans of twenty four patients with pathological proven primary colorectal carcinoma from January 1998 to December 2002 at Srinagarind hospital Khon Kaen University were review. The CT findings were analyzed according to serosal and or pericolic fat invasion, involvement of lymphnodes, liver or other metastases, and correlated the CT staging with TNM staging., Results: The CT imaging had 100% sensitivity, 57% specificity, 87.5% accuracy for evaluating serosal and/or pericolic fat invasion, 93.2% sensitivity, 54% specificity, 75% accuracy for evaluating involvement of the lymph nodes. In the present study, the distant metastases was not detected, Conclusion: The role of CT in preoperative staging of colorectal carcinoma in this report can be summarized as: (1) The sensitivity in detecting serosal and/or pericolic fat invasion is relatively higher than in previous reports. (2) The criteria for evaluation of nodal disease increased accuracy of CT and its high sensitivity is considered clinically useful.

The liver fluke, Opisthorchis viverrini, is both highly prevalent and closely associated with cholangio-carcinoma in northeast Thailand. This study measured associations between intensity of liver fluke infection and nonmalignant hepatobiliary disease diagnosed by ultrasonography among 1, 807 largely asymptomatic adult residents drawn from endemic communities. Abnormalities significantly associated with intensity of infection included gallbladder enlargerment in all dimensions, presence of sludge, irregular gallbladder wall, liver enlargement, and enhanced portal vein radicle echoes. While gallbladder enlargement was not sex-specific, the prevalence odds of the other abnormalities were 2-3 times higher among males compared with females. Those recently treated with the anthelmintic praziquantel had higher odds of these abnormalities compared with others with the same infection status who were untreated. The low prevalence of gallstones suggests that this impairment of gallbladder structure and function does not frequently stimulate gallstone formation. However, gallbladder disturbances, together with chronic inflammation and fibrosis of the bile ducts, which are visualized as enhanced portal vein radicle echoes, may contribute to the strikingly enhanced susceptibility to cholangiocarcinoma among people, especially males, with heavy liver fluke infection.