Nittaya Chamadol

Relationship between intensity of Opisthorchis viverrini infection and hepatobiliary disease detected by ultrasonography

Twenty‐four locality‐, age‐ and sex‐matched groups of village residents with no light, moderate and heavy Opisthorchis viverrini infection were examined by ultransonography. Highly significant differences were observed between the groups in the relative size of the left lobe of the liver and the fasting and post‐meal size of the gall‐bladder. In addition, indistinct gall‐bladder wall, the presence of gall‐bladder sludge and strongly enhanced portal vein radicle echoes were most frequently observed in the heavily infected group. Two suspected cases of cholangiocarcinoma were identified from the heavy group. The results highlight the importance of intensity of infection on the frequency and severity of fluke‐associated hepatobiliary disease.

Histological confirmation of periductal fibrosis from ultrasound diagnosis in cholangiocarcinoma patients

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.

A Comprehensive Public Health Conceptual Framework and Strategy to Effectively Combat Cholangiocarcinoma in Thailand

1 Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 2 Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen, Thailand, 3 Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 4 Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 5 Department of Epidemiology and Biostatistics, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand, 6 Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

Urinary microRNA-192 and microRNA-21 as potential indicators for liver fluke-associated cholangiocarcinoma risk group.

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.

Association between Diabetes Mellitus and Fatty Liver Based on Ultrasonography Screening in the World's Highest Cholangiocarcinoma Incidence Region, Northeast Thailand

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.

Teleconsultation ultrasonography: a new weapon to combat cholangiocarcinoma

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.

A Hybrid Technique of Noise Reduction with Periductal Fibrosis Ultrasound Images for Periductal Fibrosis Detection System of Cholangiocarcinoma Surveillance

The Cholangiocarcinoma (CCA) is a serious public health problem. The Periductal fibrosis (PDF) ultrasound images are applied for CCA surveillance because it is no side effect of radiation with patients, easy to portability and low cost. In contrast, the common problem of ultrasound images are speckle noise in which decreases the PDF detection performance. In this paper proposes a hybrid noise reduction method in the PDF detection system. The proposed noise reduction method by applying the Median filter and Fast Fourier transform based on PDF ultrasound images. The experimental results give the best performance for PDF detection system. A success rate of proposed method achieved at 70.89%.

Elevated Levels of Urinary 8-oxodG Correlate with Persistent Periductal Fibrosis after Praziquantel Treatment in Chronic Opisthorchiasis

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.

Current Perspectives on Opisthorchiasis Control and Cholangiocarcinoma Detection in Southeast Asia

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.

Evaluating a preoperative protocol that includes magnetic resonance imaging for lymph node metastasis in the Cholangiocarcinoma Screening and Care Program (CASCAP) in Thailand

BackgroundTreatment 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.MethodsThe 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.ResultsMRI 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).ConclusionsMRI 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.