Intraductal magnetic resonance imaging of cholangiocarcinoma - a practical possibility.

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.

Association of Cholangiocarcinoma among People with Periductal Fibrosis.

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.

New Imaging Techniques.

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.

1H NMR fecal metabolic phenotyping of periductal fibrosis- and cholangiocarcinoma-specific metabotypes defining perturbation in gut microbial-host co-metabolism.

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.

BiTNet: Hybrid deep convolutional model for ultrasound image analysis of human biliary tract and its applications.

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.

Associations between ultrasound screening findings and cholangiocarcinoma diagnosis in an at-risk population.

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.

Association between the Number of Repeated Praziquantel Treatments and Kidney Parenchymal Change in Northeast Thailand.

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.

Survival after surgery among patients with cholangiocarcinoma in Northeast Thailand according to anatomical and morphological classification.

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.

Accuracy of Nonenhanced CT vs Contrast-Enhanced CT for Diagnosis of Acute Appendicitis in Adults.

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.

Spatial analysis of hepatobiliary abnormalities in a population at high-risk of cholangiocarcinoma in Thailand.

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.

In Vitro Intraductal MRI and T2 Mapping of Cholangiocarcinoma Using Catheter Coils.

AIM: 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.

Improving the Detection of Cholangiocarcinoma: In vitro MRI-Based Study Using Local Coils and T2 Mapping.

AIM: 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.

A comparison of the proportion of early stage cholangiocarcinoma found in an ultrasound-screening program compared to walk-in patients.

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.

Discovery of Serotransferrin Glycoforms: Novel Markers for Diagnosis of Liver Periductal Fibrosis and Prediction of Cholangiocarcinoma.

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.

Urine proteomics study reveals potential biomarkers for the differential diagnosis of cholangiocarcinoma and periductal fibrosis.

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.

Discovery and Qualification of Serum Protein Biomarker Candidates for Cholangiocarcinoma Diagnosis.

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.

Association between periductal fibrosis and bile duct dilatation among a population at high risk of cholangiocarcinoma: a cross-sectional study of cholangiocarcinoma screening in Northeast Thailand.

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.

Evaluation of a short term effect of praziquantel treatment in opisthorchiasis-induced hepatobiliary inflammation by urinary 8-oxodG.

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.

Evaluation of the diagnostic performance of apparent diffusion coefficient (ADC) values on diffusion-weighted magnetic resonance imaging (DWI) in differentiating between benign and metastatic lymph nodes in cases of cholangiocarcinoma.

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 mm2/s) LNs were not significantly different from those of non-metastatic LNs (1.29 × 10-3 mm2/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.

Characterisation of the Urinary Metabolic Profile of Liver Fluke-Associated Cholangiocarcinoma.

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.