• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.2
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• pp.123-130
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• 2023

Intrahepatic cholangiocarcinoma is an aggressive, often fatal, malignancy that arises from the bile ducts. As it often presents with metastatic disease, surgery has limited utility. However, in some cases, neoadjuvant chemotherapy has provided the necessary reduction in tumor burden to allow for adequate resection. Consequently, new advances in neoadjuvant chemoradiation and targeted therapy are of interest with numerous case reports and small series published routinely; it is challenging to present a large case series or study given the overall rare frequency with which this malignancy is seen. Herein, we aim to summarize the newest advances in both neoadjuvant chemotherapy and targeted immunotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9511-9515
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• 2014

Cholangiocarcinoma (CCA) is a cancer of the bile duct epithelial cells. The highest incidence rate of CCA with a poor prognosis and poor response to chemotherapy is found in Southeast Asian countries, especially in northeastern Thailand and Lao PDR. Cathepsin B is a lysosomal cysteine protease which is regulated by cysteine proteinase inhibitors such as cystatin C. Elevation of cathepsin B levels in biological fluid has been observed in patients with inflammatory diseases and many cancers. We aimed to investigate the serum cathepsin B and cystatin C levels of CCA patients to evaluate the feasibility of using cathepsin B and cystatin C as markers for the diagnosis of CCA. Fifty-six sera from CCA patients, 17 with benign biliary diseases (BBD) and 13 from controls were collected and the cathepsin B and cystatin C levels were determined. In addition, cathepsin B expression was investigated immunohistochemically for 9 matched-pairs of cancerous and adjacent tissues of CCA patients. Serum cathepsin B, but not cystatin C, was significantly higher in CCA and BBD patient groups compared to that in the control group. Consistently, all cancerous tissues strongly expressed cathepsin B while adjacent tissues were negative in 7 out of 9 cases. In contrast, serum cystatin C levels were comparable between CCA and control groups, although serum cystatin C levels in the BBD group was higher than that in the control or CCA groups. When the serum cathepsin B to cystatin C ratio was calculated, that of the CCA group was significantly higher than that of the control group, and, although statistically not significant, the ratio of CCA group showed a trend to be higher than that of the BBD group. Thus, the cathepsin B to cystatin C ratio might be used as an alternative marker for aiding diagnosis of CCA.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2889-2894
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• 2016

This study aimed to modify behavior regarding liver fluke and cholangiocarcinoma prevention in Chumphuang district, Nakhon Ratchasima province, Thailand through integrated learning. A total of 180 participants were included through purposive selection of high-risk scores on verbal screening. Participants attended the health education program which applied the health belief model included family based, knowledge station based, academic merit based and community based learning. Data were collected using a questionnaire composed of 4 parts: 1) personal information, 2) knowledge, 3) perceived susceptibility, severity, benefits, and barriers, 4) practice regarding liver fluke and cholangiocarcinoma prevention. The result revealed that the majority were female (79.9%), age ${\geq}60$ years old (33.2%), primary school educational level (76.1%), and agricultural occupation (70.1%). The mean scores of knowledge, perception, and practice to liver fluke and cholangiocarcinoma prevention, before participated the integrative learning were low, moderate, and low, respectively. Meanwhile, the mean score of knowledge, perceived susceptibility, severity, benefits, and barriers, and practice regarding liver fluke and cholangiocarcinoma prevention, were higher with statistical significance after participation in the integrated learning. This finding indicates that health education programs may successfully modify health behavior in the rural communities. Therefore they may useful for further work behavior modification in other epidemic areas.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1367-1370
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• 2015

Diagnosis of cholangiocarcinoma (CCA) is difficult when patients do not show jaundice. The aim of this study was to examine the feasibility of using the total serum bile acid (TSBA) level as an aid for the diagnosis of CCA in patients without jaundice. For this purpose, TSBA of the following groups were measured using a Beckman Synchron CX4 clinical chemistry analyzer: 60 cases of CCA with total serum bilirubin ${\leq}2mg/dL$ (low total bilirubin group, LTB); 32 cases of CCA with total serum bilirubin >2 mg/dL (high total bilirubin group, HTB); and 115 healthy controls. Liver function parameters such as serum cholesterol, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were also examined. The results showed that the TSBA of both LTB and HTB groups of the CCA patients were significantly higher than that of the healthy controls. Also, significant correlation was observed between TSBA and total bilirubin levels in the HTB group of CCA patients. However, no such correlation was seen in the LTB group. The cut-off value of TSBA was determined for the LTB group of CCA patients using the receiver operating characteristic curve analysis, and it was $6.05{\mu}mol/L$ with the sensitivity and specificity of 46.7% and 84.4%, respectively. In addition, the ALP level was correlated well with the TSBA level and ALP in HTB group was significantly higher than that of LTB group. Moreover, the combination of high TSBA and high ALP levels gave higher specificity up to 97.4%. TSBA might be useful for the diagnosis of CCA patients without jaundice.

• Journal of Sasang Constitutional Medicine
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• v.25 no.4
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• pp.432-441
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• 2013

Objectives Despite the treatment with antibiotics, patients with sepsis has a high mortality (80%) in the underlying disease group. The aim of this study was to report the improvement of septic condition of the cholangiocarcinoma patient after the treatment with Handayeolso-tang, Fel Tauri, and antibiotics. Methods We retrospectively reviewed the medical records. The patient's subjective symptoms such as chilling and abdominal pain were evaluated by NRS and the performance status was evaluated by ECOG. This case was literally compared with relevant published studies on prognosis of sepsis. Results Despite poor prognostic factor(MEDS score 18), the patient's symptoms such as fever, chilling, abdominal pain, and diarrhea and ECOG(Eastern Cooperative Oncology Group) improved. The patient was hemodynamically stabilized on 3rd day from the treatment, and her laboratory test results were normalized on 7th day. Conclusions A female patient of metastatic cholangiocarcinoma came to the hospital for cholangitis, later causing septic shock. Both her symptoms and laboratory tests showed significant improvement after the treatment of antibiotics, Handayeolso-tang and Fel Tauri. To our knowledge, this is the first case reporting the synergistic combination of Korean oriental medicine and Western medicine approaching to sepsis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3473-3477
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• 2013

Background: Primary liver cancer (PLC) is the fifth most common malignancy worldwide and is still associated with high mortality. Hepatocellular carcinoma (HCC) and cholangiocarcinoma are the two most common PLCs, and their incidence varies across regions. Currently there are no published data available on the incidence of PLC in Brunei Darussalam. Materials and Methods: All proven PLCs between 2000 and 2009 were identified from the National Cancer Registry and reviewed. Metastatic diseases were excluded. A total of 123 cases (male 65.8%, female 34.2%) were identified and their data collected for calculation of the age standardised rate (ASR). Results: The most common type of PLC was HCC (87.8%) followed by cholangiocarcinoma (10.6%). There were two cases of hepatoblastoma. The mean age at diagnosis was 63.2 years. The overall ASR of PLC was 8.2/100,000, increasing from 4.5/100,000 population in 2000 to 11.4/100,000 population in 2009. The rates were higher among males (12.0/100,000) than females (4.7/100,000). Among the ethnic groups, Chinese had the highest rates (overall 13.1/100,000 with none recorded in 2000 to 30.3/100,000 in 2009) compared to the Malays (overall 8.5/100,000 increasing from 4.5/100,000 in 2000 to 12.3/100,000 in 2009) and the indigenous groups. The incidence increased after the age of 50 and was highest among the 75-79 age groups. Increase was seen for HCC but not for cholangiocarcinoma. Conclusions: The most common type of PLC is HCC and the annual incidence of PLC is increasing in Brunei Darussalam,rates being higher in males and Chinese.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1737-1742
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• 2015

Background: Mitochondrial DNA (mtDNA) mutations have been shown to be associated with cancer. This study explored whether mtDNA mutations enhance cholangiocarcinoma (CCA) development in individuals. Materials and Methods: The whole mitochondrial genome sequences of 25 CCA patient tissues were determined and compared to those of white blood cells from the corresponding individuals and 12 healthy controls. The mitochondrial genome was amplified using primers from Mitoseq and compared with the Cambridge Reference Sequence. Results: A total of 161 mutations were identified in CCA tissues and the corresponding white blood cells, indicating germline origins. Sixty-five (40%) were new. Nine mutations, representing those most frequently observed in CCA were tested on the larger cohort of 60 CCA patients and 55 controls. Similar occurrence frequencies were observed in both groups. Conclusions: While the correspondence between the cancer and mitochondrial genome mutation was low, it is of interest to explore the functions of the missense mutations in a larger cohort, given the possibility of targeting mitochondria for cancer markers and therapy in the future.

• Molecules and Cells
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• v.43 no.5
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• pp.491-499
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• 2020

Hippo signaling acts as a tumor suppressor pathway by inhibiting the proliferation of adult stem cells and progenitor cells in various organs. Liver-specific deletion of Hippo pathway components in mice induces liver cancer development through activation of the transcriptional coactivators, YAP and TAZ, which exhibit nuclear enrichment and are activated in numerous types of cancer. The upstream-most regulators of Warts, the Drosophila ortholog of mammalian LATS1/2, are Kibra, Expanded, and Merlin. However, the roles of the corresponding mammalian orthologs, WWC1, FRMD6 and NF2, in the regulation of LATS1/2 activity and liver tumorigenesis in vivo are not fully understood. Here, we show that deletion of both Wwc1 and Nf2 in the liver accelerates intrahepatic cholangiocarcinoma (iCCA) development through activation of YAP/TAZ. Additionally, biliary epithelial cell-specific deletion of both Lats1 and Lats2 using a Sox9-Cre^ERT2 system resulted in iCCA development through hyperactivation of YAP/TAZ. These findings suggest that WWC1 and NF2 cooperate to promote suppression of cholangiocarcinoma development by inhibiting the oncogenic activity of YAP/TAZ via LATS1/2.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.557-563
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• 2013

Intrahepatic cholangiocarcinoma (ICC) is ranked as one of the top five causes of cancer-related deaths. ICC in Thai patients is associated with infection with the liver fluke, Opisthorchis viverrini, but the molecular basis for development remains unclear. The present study employed a microarray approach to compare gene expression profiles of ICCs and normal liver tissues from the same patients residing in Northeast Thailand, a region with a high prevalence of liver fluke infection. In ICC samples, 2,821 and 1,361 genes were found to be significantly up- and down-regulated respectively (unpaired t-test, p<0.05; fold-change ${\gep}2.0$). For validation of the microarray results, 7 up-regulated genes (FXYD3, GPRC5A, CEACAM5, MUC13, EPCAM, TMC5, and EHF) and 3 down-regulated genes (CPS1, TAT, and ITIH1) were selected for confirmation using quantitative RT-PCR, resulting in 100% agreement. The metallothionine heavy metal pathway contains the highest percentage of genes with statistically significant changes in expression. This study provides exon-level expression profiles in ICC that should be fruitful in identifying novel genetic markers for classifying and possibly early diagnosis of this highly fatal type of cholangiocarcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4131-4136
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• 2016

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 (${\geq}70$ years) (ORadj = 1.28, 95% CI: 1.14 - 1.44, p < 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, p < 0.001) and diabetes mellitus (ORadj = 0.57, 95% CI: 0.49 - 0.65, p < 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.