• Journal of Yeungnam Medical Science
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• v.33 no.2
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• pp.77-84
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• 2016

Pancreatic cancer, the 4th leading cause of cancer-related death in the United States, has a very poor prognosis. Cholangiocarcinoma originates from either intrahepatic or extrahepatic bile duct, and its incidence is gradually increasing worldwide. Endoscopic retrograde cholangiopancreatography with brush cytology has a high false-negative rate for the diagnosis of biliary malignancy. Recently, endoscopic ultrasonography (EUS) has emerged as the potential modality to detect pancreatic cancer. EUS-guided fine needle aspiration for cytologic analysis made it possible to overcome the obstacle in differentiating between benign and malignant lesions in the pancreatobiliary lesion, and it has been well established as a safe and effective procedure. Herein, the clinical application of EUS in the diagnosis of pancreatobiliary cancer was reviewed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3043-3050
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• 2015

The tumor microenvironment (TME) includes numerous non-neoplastic cells such as leukocytes and fibroblasts that surround the neoplasm and influence its growth. Tumor-associated macrophages (TAMs) and cancerassociated fibroblasts (CAFs) are documented as key players in facilitating cancer appearance and progression. Alteration of the macrophage (CD68, CD163) and fibroblast (${\alpha}-SMA$, FSP-1) cells in Opisthorchis viverrini (Ov) -induced cholangiocarcinoma (CCA) was here assessed using liver tissues from an established hamster model and from 43 human cases using immunohistochemistry. We further investigated whether M2-activated TAMs influence CCA cell migration ability by wound healing assay and Western blot analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+, CD163+) and CAFs (${\alpha}-SMA+$, FSP-1+), respectively in the early stages of carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is significantly associated with the presence of extrahepatic metastases (p=0.021). Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they may be representative of an epithelial-to-mesenchymal transition (EMT) with increased metastatic activity. We further showed that M2-TAM conditioned medium can induce CCA cell migration as well as increase N-cadherin expression (mesenchymal marker). The present work revealed that significant TME changes occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key factors contributing to CCA metastasis, possibly via EMT processes.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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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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• v.13 no.5
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• pp.1963-1969
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• 2012

Objectives: Recent data show that the metabolic syndrome may play a role in several cancers, but the etiology for biliary tract cancer is incompletely defined. The present aim was to evaluate risk factors for biliary tract cancer in China. Methods: A case-control study in which cases were biliary tract cancer patients referred to Peking Union Medical College Hospital (PUMCH). Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of PUMCH. Data on the metabolic syndrome, liver diseases, family history, and history of diabetes and hypertension were collected by retrospective review of the patients' records and health examination reports or by interview. Results: A total of 281 patients (102 intrahepatic cholangiocarcinoma (ICC), 86 extrahepatic cholangiocarcinoma (ECC) and 93 gallbladder carcinoma (GC)) and 835 age- and sex-matched controls were enrolled. $HBsAg^+/anti-HBc^+$ (P=0.002), history of diabetes (P=0.000), cholelithiasis (P=0.000), TC (P=0.003), and HDL (P=0.000) were significantly related to ICC. Cholelithiasis (P=0.000), Tri (P=0.001), LDL (P=0.000), diabetes (P=0.000), Apo A (P=0.000) and Apo B (P=0.012) were significantly associated with ECC. Diabetes (P=0.017), cholelithiasis (P=0.000) and Apo A (P=0.000) were strongly inversely correlated with GC. Conclusion: Cholelithiasis, HBV infection and metabolic symptoms may be potential risk factors for the development of biliary tract cancer.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.3
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• pp.251-257
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• 2023

Backgrounds/Aims: This is a retrospective analysis of whether the 8th edition American Joint Committee on Cancer (AJCC) was a significant improvement over the 7th AJCC distal extrahepatic cholangiocarcinoma classification. Methods: In total, 111 patients who underwent curative resection of mid-distal bile duct cancer from 2002 to 2019 were included. Cases were re-classified into 7th and 8th AJCC as well as clinicopathological univariate and multivariate, and Kaplan-Meier survival curve and log rank were calculated using R software. Results: In patient characteristics, pancreaticoduodenectomy/pylorus preserving pancreaticoduodenectomy had better survival than segmental resection. Only lymphovascular invasion was found to be significant (hazard ratio 2.01, p = 0.039) among all clinicopathological variables. The 8th edition AJCC Kaplan Meier survival curve showed an inability to properly segregate stage I and IIA, while there was a large difference in survival probability between IIA and IIB. Conclusions: The 8th distal AJCC classification did resolve the anatomical issue with the T stage, as T1 and T3 showed improvement over the 7th AJCC, and the N stage division of the N1 and N2 category was found to be justified, with poorer survival in N2 than N1. Meanwhile, in TMN staging, the 8th AJCC was able differentiate between early stage (I and IIA) and late stage (IIB and III) to better explain the patient prognosis.

• Parasites, Hosts and Diseases
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• v.45 no.2 s.142
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• pp.77-85
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• 2007

Among several diagnostic tools for clonorchiasis (Clonorchis sinensis infection), radiologic examinations are commonly used in clinical practices. During the 2 past decades, many reports regarding imaging findings of clonorchiasis were introduced. The basic imaging finding of clonorchiasis is diffuse dilatation of the peripheral intra-hepatic bile ducts, without dilation of the large intrahepatic or extrahepatic bile ducts. By this finding, however, active clonorchiasis cannot be differentiated from cured infection. Some recent radiologic studies suggested specific findings of active clonorchiasis. Besides direct demonstration of worms, increased periductal echogenicity on sonography and periductal enhancement on dynamic contrast-enhanced CT or MR imaging possibly represent active clonorchiasis. Those images of the liver clonorchiasis are known to be correlated with worm burdens (EPG counts) in their frequency and also severity. The images of cholangiocarcinoma associated with clonorchiasis show both the tumor with obstruction images and diffuse dilatation of the peripheral intrahepatic bile ducts. Radiological images can be a good practical alternative diagnostic method of clonorchiasis.

• Clinical Endoscopy
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• v.56 no.2
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• pp.135-142
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• 2023

Endoscopic biliary drainage strategies for managing unresectable malignant hilar biliary obstruction differ in terms of stent type, drainage area, and deployment method. However, the optimal endoscopic drainage strategy remains unclear. Uncovered self-expandable metal stents (SEMS) are the preferred type because of their higher functional success rate, longer time to recurrent biliary obstruction (RBO), and fewer cases of reintervention than plastic stents (PS). Other PS subtypes and covered SEMS, which feature a longer time to RBO than PS, can be removed during reintervention for RBO. Bilateral SEMS placement is associated with a longer time to RBO and a longer survival time than unilateral SEMS placement. Unilateral drainage is acceptable if a drainage volume of greater than 50% of the total liver volume can be achieved. In terms of deployment method, no differences were observed in clinical outcomes between side-by-side (SBS) and stent-in-stent deployment. Simultaneous SBS boasts a shorter procedure time and higher technical success rate than sequential SBS. This review of previous studies aimed to clarify the optimal endoscopic biliary drainage strategy for unresectable malignant hilar biliary obstruction.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.4
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• pp.317-322
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• 2009

Purpose: $^{18}$F-flurodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumor aggressiveness and prognosis in various types of cancer. However, pattern of FDG uptake in biliary malignancies and its clinical significance have not been studied well. The purpose of this study was to assess the additional value of $^{18}$F-FDG PET in differential diagnosis and prognosis of cholangiocarcinoma (CC) according to the tumor location and tumor morphology. Materials and Methods: From April 2005 to May 2008, eighty two patients (M:F = 55:27, age 66.2$\pm$9.6 yrs) with CC underwent $^{18}$F-FDG PET. For semiquantitative analysis, the maximum standardized uptake value (SUV$_{max}$) was obtained from the primary tumor. The difference of SUV$_{max}$ according to the tumor location and tumor growth pattern, such as scirrhous type, nodular type, polypoid type were compared. Results: Overall sensitivity of PET scan was 81.7% in CC. SUV$_{max}$ on PET scan in intrahepatic CC was significantly higher compared to extrahepatic CC. In extrahepatic CC, polypoid type showed significantly higher SUV$_{max}$ compared to scirrhous type. Conclusion: $^{18}$F-FDG PET may have a significant impact on clinical decision-making and on the management of intrahepatic cholangiocarcinoma. And it is related to the shape of the tumor and the sensitivity of detection is higher in the mass-forming type than in the scirrhous type.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.49-58
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• 1992

From January 1985 to September 1990, 7 patients with carcinoma of the extrahepatic biliary system received external radiaiton therapy combined with hyperthermia. Of the 3 patients with extrahepatic bile duct cancer, two were primary cholangiocarcinoma and one was metastatic peripancreatic carcinoma. Of the 4 patients with carcinoma of the gallbladder, two were locor-egionally advanced and unresectable carcinoma and the remaining two were local-regional recurrence after cholecystectomy. They were all pathologicallly proven adenocarcinoma. The radiation dose received ranged from 3000 cGy/2weeks to 5040 cGy/7 weeks. The hyperthermia was done once or twice a week and 4 to 12 sessions in total. The tumor response was confirmed by T-tube cholangiography, percutaneous transhepatic cholangiography and CT scan. 6 out of 7 ($86\%$) showed partial regression of the tumor. The median survival time was 7 months (range $4\~11$ months).6 out of 7 patients were dead: one died of septicemia, 4 of primary disease, one of distant metastases. Only one out of 7 patients is still alive but new metastatic lesion was found. There was not any treatment related deaths. There was also no evidence of treatment related problems with liver, stomach and duodenum, although the observation period was short.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.37-44
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• 2016

Several infectious agents are considered to be causes of cancer in human, mainly hepatitis B and C viruses, high-risk human pailloma viruses, Helicobacter pylori, Clonorchis sinensis, and Opisthorchis viverrini. Here we described the evident research and the association between Helicobacter spp. and biliary tract cancer particularly cholangiocarcinoma (CCA). Global epidemiological studies have suggested that Helicobacter spp. are possible risk factors for biliary tract diseases. Molecular studies support a linkage of Helicobacter spp. with CCA development. H. pylori, H. bilis, and H. hepaticus, are found in CCA, but the most common species are H. pylori and H. bilis. The type of CCA are associated with Helicobacter spp. include extrahepatic CCA, and common bile duct cancer. Up to the present, however, the results from different regions, materials and methods, sub-sites of cancer, and controls have not been consistent, thus introducing heterogeneity. Therefore, a comparison between co-Helicobacter spp.-CCA in the countries with low and high incident of CCA is required to settle the question. Furthermore, clarifying variation in the role of Helicobacter species in this CCA, including pathogenesis of CCA through enhanced biliary cell inflammation and proliferation, is necessary.