• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1163-1168
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• 2016

Cholangiocarcinoma (CCA) is the bile duct cancer which constitutes one of the important public health problems in Thailand with high mortality rate, especially in the Opisthorchis viverrini (a parasite risk factor for CCA) endemic area of the northeastern region of the country. This study aimed to identify potential biomarkers from the plasma peptidome by CCA patients. Peptides were isolated using 10 kDa cut-off filter column and the flow-through was then used as a peptidome for LC-MS/MS analysis. A total of 209 peptides were obtained. Among these, 15 peptides were concerned with signaling pathways and 12 related to metabolic, regulatory, and biosynthesis of secondary metabolite pathways. Five exclusive peptides were identified as potential biomarkers, i.e. ETS domain-containing transcription factor ERF (P50548), KIAA0220 (Q92617), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 (P42338), LP2209 (Q6XYC0), and casein kinase II subunit alpha (P19784). Three of these biomarkers are signaling related molecules. A combination of these biomarkers for CCA diagnosis is proposed.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3931-3936
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• 2015

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 (${\pm}9.25$) 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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6175-6179
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• 2012

Intestinal parasitic infections (IPIs) are still important to the health of Thai rural residents. IPIs are the cause of many chronic diseases with, for example, opisthorchiasis resulting in progression to cholangiocarcinoma (CCA). This cross-sectional study in a prospective cohort study aimed to examine the prevalence and co-infection of intestinal parasites among Northeastern Thai rural residents, recruited into the Khon Kaen Cohort Study (KKCS), and who were residing in areas of high-risk for developing CCA. On recruitment, subjects had completed questionnaires and provided fecal samples for IPI testing using the formalin ethyl acetate concentration technique. Data on selected general characteristics and the results of the fecal tests were analysed. IPI test results were available for 18,900 of cohort subjects, and 38.50% were found to be positive for one or more types of intestinal parasite. The prevalence of Opisthorchis viverrini (O. viverrini) infection was the highest (45.7%), followed by intestinal flukes (31.9%), intestinal nematodes (17.7%), intestinal protozoa (3.02%), and intestinal cestodes (1.69%). The pattern of different infections was similar in all age groups. According to a mapping analysis, a higher CCA burden was correlated with a higher prevalence of O. viverrini and intestinal flukes and a greater intensity of O. viverrini. Both prevention and control programs against liver fluke and other intestinal parasites are needed and should be delivered simultaneously. We can anticipate that the design of future control and prevention programmes will accommodate a more community-orientated and participatory approach.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.7029-7032
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• 2013

Background: Cholangiocarcinoma (CCA) is a very common cancer in Northeastern Thailand. Most CCA patients see a physician at a late stage when curative surgery is not possible. After diagnosis, they generally are treated by partial surgery/percutaneous drainage, chemotherapy and supportive treatment. Objective: This study aimed to assess the survival rates of CCA patients after supportive treatment. Methods: A retrospective cohort design was applied in this study. Data for 746 CCA patients were extracted from the hospital-based cancer registry of Srinagarind Hospital, Khon Kaen University. The patients were diagnosed (at least by ultrasonography) between 1 January, 2009 and 31 December, 2009 and then followed up for current status until 30 June, 2011. The cumulative survival rate was calculated by the Kaplan-Meier method, and independent prognostic factors were investigated using Cox regression. Results: The total follow-up time was 5,878 person-months, and the total number of deaths was 637. The mortality rate was therefore 10.8 per 100 person-year (95%CI : 10.1-11.7). The cumulative 3, 6, 9, 12 and 24 month survival rates were 59%, 39%, 31%, 24% and 14%, respectively. The median survival time after supportive treatment was 4 months. After adjusting for gender, age, stage, distant metastasis, histological grading and treatment, stage was a significant predictor of survival of CCA patients. Those in stage III and stage IV had a 6.78 fold higher mortality than the stage I and stage II cases (95% CI : 1.6-28.7). Conclusion: It is very important to encourage patients to see health personnel at an early stage.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.7011-7016
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• 2013

Background: The liver fluke, Opisthorchis viverrini, and the associated incidence of subsequent cholangiocarcinoma (CCA) are still a public health problem in Thailand, and praziquantel (PZQ) remains the antihelminthic drug of choice for treatment. Evidence in hamsters shows that repeated infection and PZQ treatments could increase the risk of CCA. However, the existing evidence in humans is inconclusive regarding increased risk of CCA with frequency of PZQ intake. Objectives: To investigate the relationship between number of repeated PZQ treatments and CCA in patients with O viverrini infection. Materials and Methods: The reviewed studies were searched in EMBASE, MEDLINE, ProQuest, PubMed and SCOPUS from inception to October, 2012 using prespecified keywords. The risk of bias (ROB) of included studies was independently assessed by two reviewers using a quality scale from the Newcastle-Ottawa Scale (NOS). Risk effect of PZQ was estimated as a pooled odds ratio (OR) with its 95% confidence interval (95%CI) in the random-effects model using DerSimonian and Laird's estimator. Results: Three studies involving 637 patients were included. Based on the random effects model performed in two included studies of 237 patients, the association between PZQ treatments and CCA was not statistical significant with a pooled OR of 1.8 (95%CI; 0.81 to 4.16). Conclusions: The present systematic review and meta-analysis provides inconclusive evidence of risk effect of PZQ on increasing the risk of CCA and significant methodological limitations. Further research is urgently needed to address the shortcomings found in this review, especially the requirement for histological confirmation.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.401-406
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• 2016

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.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.201-205
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• 2016

Cholangiocarcinoma (CCA) is generally a rare primary liver tumor of the bile duct with extremely poor clinical outcomes due to late diagnosis. Osteopontin (OPN) is the most abundant expressed gene in intrahepatic CCA and its involvement in tumor aggressiveness suggests it could be a useful prognostic biomarker. However, the prognostic significance of OPN expression in CCA is still controversial. We therefore immunohistochemically studied OPN expression in 354 resected CCAs and correlated the results with patient clinicopathological parameters. OPN expression was separately scored according to the percentage of cancer cells or degree of stromal tissue staining and classified as low (score 0-1) and high (score 2-3). OPN expression in CCA cells was found in 177 out of 354 patients (56.5%), whereas stroma was positive in 185 out of 354 patients (52.3%). Univariate analysis with several of the aforementioned parameters revealed that stromal but not cancer cell OPN expression was significantly associated with tumor size, tumor direct invasion into normal liver parenchyma, regional lymph node metastasis and higher staging. The combination of cancer cell and stromal OPN expression demonstrated a positive trend for linkage with lymph node metastasis. Multivariate analysis identified gender, the presence of lymphatic permeation and lymph node metastasis, but not OPN expression, as independent prognostic factors. This study confirms the presence of stromal OPN expression in tumor aggressiveness but not survival in CCA patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5875-5881
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• 2015

Cholangiocarcinoma (CCA) is a rare but highly fatal cancer for which the molecular mechanisms and diagnostic markers are obscure. We therefore investigated the kinetic expression of isocitrate dehydrogenase-1 (IDH1), isocitrate dehydrogenase-2 (IDH2) and homogentisate 1,2-dioxygenase (HGD) during the tumorigenesis of O. viverrini infection-associated CCA in an animal model, and confirmed down-regulation of expression in human cases of opisthorchiasis-associated CCA through real time PCR. Kinetic expression of HGD, IDH1 and IDH2 in the animal model of O. viverrini infection-induced CCA was correlated with human CCA cases. In the animal model, expression of HGD was decreased at all time points (p<0.01) and expression of both IDH1 and IDH2 was decreased in the CCA group. In human cases, expression of HGD, IDH1 and IDH2 was decreased more than 2 fold in 55 cases (70.5%), 25 cases (32.1%) and 24 cases (30.8%) respectively. The present study suggests that reduction of HGD, IDH1 and IDH2 may be involve in cholangiocarcinoma genesis and may be useful for molecular diagnosis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3477-3482
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• 2014

Objective: Patients with inflammatory bowel disease (IBD) have an increased risk of extra-intestinal cancer, whereas its impact on cholangiocarcinoma (CC) remains unknown. The aim of this study was to obtain a reliable estimate of the risk of CC in IBD patients through a meta-analysis of clinical observational studies. Methods: Relevant studies were retrieved by searching PUBMED, EMBASE and Web of Science Databases up to Dec 2013. Four population-based case-control and two cohort studies with IBD were identified. Summary relative risk (RR) and its corresponding 95% confidence interval (CI) were calculated using a random-effects model. Potential sources of heterogeneity were detected using subgroup analyses. Results: The pooled risk estimate indicated IBD patients were at increased risk of CC (RR = 2.63, 95%CI = 1.47-4.72). Moreover, the increased risk of CC was also associated with Crohn's disease (RR = 2.69, 95%CI = 1.59-4.55) and ulcerative colitis (RR = 3.40, 95%CI = 2.50-4.62). In addition, site-specific analyses revealed that IBD patients had an increased risk of intrahepatic CC (ICC) (RR = 2.61, 95%CI = 1.72-3.95) and extrahepatic CC (ECC) (RR = 1.47, 95%CI = 1.10-1.97). Conclusions: This study suggests the risk of CC is significantly increased among IBD patients, especially in ICC cases. Further studies are warranted to enable definite conclusions to be drawn.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5953-5956
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• 2013

Background: Cholangiocarcinoma (CCA) is the most common cancer in Northeast Thailand. It is also a crucial health problem for Thai people. Various risk factors for CCA have been identified in the upper part of Northeast Thailand, but no similar studies of risk factors have been conducted in the lower parts of the region. This study aimed to investigate factors associated with CCA in the resident population. Materials and Methods: A hospital-based case-control study was conducted during 2009-2012 with the recruitment of 123 CCA cases and 123 non-CCA patient controls, matched for sex, age and residential area. Information was collected by interview with a structured questionnaire. Blood samples were collected for assays of anti-OV antibodies. Associations between various personal factors, dietary habits, family history, the presence of anti-OV antibodies and CCA were analyzed using multiple conditional logistic regression. Results: Patients who consumed raw meat (beef, pork) and alcoholic beverages ${\geq}3$ times per week had a higher risk of CCA than non-consumers ($OR_{adj}$=4.33; 95%CI=1.14-16.35 and $OR_{adj}$=2.13; 95%CI=1.00-4.55, respectively). Patients who had a family history of cancer had a higher risk than those who did not ($OR_{adj}$=4.34; 95%CI=1.80-10.43). Also, patients who had anti-OV antibodies (AU>23.337) had a higher risk than those whose anti-OV antibodies were below the cut-off ($AU{\leq}23.34$) ($OR_{adj}$=3.09; 95%CI=1.04-9.16). Conclusions: As is the case in the upper part of Northeast Thailand, OV infection is a crucial risk factor for CCA in people who live in lower part of the region. Similarly, a family history of cancer and the consumption of alcohol are risk factors for CCA.