• 한국독성학회:학술대회논문집
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• 한국독성학회 2006년도 추계학술대회
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• pp.32-33
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• 2006

There is compelling evidence that chronic inflammation predisposes to biliary tract cancer. Previously we found that aspirin use and variants in the PTGS2 gene, both of which are closely linked to inflammation, were associated with biliary tract cancer risk in a population-based study in China. To test the inflammation hypothesis further, we examined the associations of variants in 20 genes involved in the inflammation pathway with risk of biliary tract cancer and stones in a large population-based case-control study in Shanghai, China. We genotyped 56 single nucleotide polymorphisms (SNPs)from 20 inflammation genes in 411 biliary tract cancer cases (237 gallbladder cancers, 127 extrahepatic bile duct cancers, and 47 ampullary cancers), 895 subjects with biliary stones, and 786 population controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (Cls) for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer risk. Of the 56 SNPs examined, 20 showed some associations with biliary cancer and stones. Specifically, variants of the IL8, IL8RB, RNASEL, TGF-beta, and TNF-alpha genes were associated with gallstone risk, while variants in the IL1A, IL10, VEGF, and RNASEL genes were associated with gallbladder cancer risk. Adjustment for multiple comparisons did not materially change these results. Of the 10 genes with multiple SNPs, we inferred halotypes; only one haplotype in the IL8RBgene was associated with gallstones. The haplotype frequency was significantly different between bile dict cancer cases and control (p=0.007). A haplotype comprising 3 SNPs in the IL8RB gene (rs2230054, rs1126579, rs1126580) was associated with a 54% increased risk of bile duct stones (95% CI 1.14-2.07, p=0.02), relative to the most frequent haplotype. In summary, common variants in immune-related genes influencing inflammatory responeses were associated with gallstones and biliary tract cancer, lending further support to the role of inflammation in the pathogenesis of biliary stones and biliary tract cancer. Future larger studies with more complete gene coverage are needed to confirm these results.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6135-6140
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• 2015

Background: The aim of this meta-analysis was to assess the efficacy of the apparent diffusion coefficient (ADC) value of diffusion-weighted MRI (DWI) for differentiating biliary tract cancer (BTC) from benign biliary tract diseases in Asians. Materials and Methods: We systematically searched Embase and PubMed prior to December 2014. Eight studies conducted in Asians met our predetermined inclusion criteria. Results: Our meta-analysis results showed that ADC values in BTC tissues were significantly lower than in benign biliary tract tissues (SMD = -1.54, 95%CI: -1.75~-1.33, P<0.001). Subgroup analysis based on the MRI machine type showed that the ADC values were consistent, accurate and reliable in the diagnosis of BTC when comparing cancer tissue vs. benign tissue under the Siemens 1.5 T/3.0 T, Philips 1.5 T/3.0 T, GE 1.5 T, and Toshiba 1.5 T types, respectively (all P<0.05). Further, ADC values were still consistent and accurate in the differential diagnosis of BTC under the b value of 800 and $1000s/mm^2$ (all P<0.05). Conclusions: Our findings supported potential clinical applications of DWI ADC values in differentiating BTC from benign biliary tract diseases in Asians.

• 대한한방내과학회지
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• 제33권4호
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• pp.587-598
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• 2012

Objectives : This study was performed to elucidate the pro-apoptotic effect of Artemisiae capillaris herba extracted with ethanol on biliary tract cancer cells. Materials and Methods : The biliary tract cancer cell line SNU-1196 was used in this study. Cells were treated with different concentrations of Artemisiae capillaris herba for 24, 48 and 72 hours. After the treatment, cell viability, apoptosis, caspase activities and the mRNA expressions of the Bcl-2, Bax, P53, and P21 were measured by using MTT assay, cell cycle analysis, apoptosis assay, and RT-PCR. The cell cycle analysis was done by flow cytometry and apoptosis assay by cell death detection ELISA kit. Results : Artemisiae capillaris herba inhibited proliferation of SNU-1196 in long-time culture group with dose-dependent manner. All cells treated with Artemisiae capillaris herba showed increased apoptosis with dose- and time-dependent manner. Exposure of SNU-1196 to Artemisiae capillaris herba induced caspase-3 activation. However, apeoptosis was blocked when SNU-1196 was treated together with the pan-caspase inhibitor Z-VAD-FMK and the caspase-3 inhibitor Z-DEVE-FMK. After the treatment of Artemisiae capillaris herba, the mRNA expressions of caspase -3, -8, -9, p53, and p21 was increased in all cells. Artemisiae capillaris herba resulted in a significant decrease in Bcl-2 and an increase in Bax mRNA levels. Conclusions : These results suggest that Artemisiae capillaris herba would be beneficial in the treatment of biliary tract cancer.

• Radiation Oncology Journal
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• 제37권4호
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• pp.279-285
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• 2019

Purpose: This study was conducted to compare the outcome of three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for the postoperative treatment of biliary tract cancer. Materials and Methods: From February 2008 to June 2016, 57 patients of biliary tract cancer treated with curative surgery followed by postoperative 3D-CRT (n = 27) or IMRT (n = 30) were retrospectively enrolled. Results: Median follow-up time was 23.6 months (range, 5.2 to 97.6 months) for all patients and 38.4 months (range, 27.0 to 89.2 months) for survivors. Two-year recurrence-free survival is higher in IMRT arm than 3D-CRT arm with a marginal significance (25.9% vs. 47.4%; p = 0.088). Locoregional recurrence-free survival (64.3% vs. 81.7%; p = 0.122) and distant metastasis-free survival (40.3% vs. 55.8%; p = 0.234) at two years did not show any statistical difference between two radiation modalities. In the multivariate analysis, extrahepatic cholangiocarcinoma, poorly-differentiated histologic grade, and higher stage were significant poor prognostic factors for survival. Severe treatment-related toxicity was not significantly different between two arms. Conclusions: IMRT showed comparable results with 3D-CRT in terms of recurrence, and survival, and radiotherapy toxicity for the postoperative treatment of biliary tract cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9687-9692
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• 2014

Background: Biliary tract cancers are rare, and surgical resection is the standard treatment at early stages. However, reports on the benefits of adjuvant treatment following surgical resection are conflicting. This study aimed to evaluate the factors affecting survival and adjuvant treatments in patients with surgically treated biliary tract cancers. Materials and Methods: Patient clinical features, adjuvant treatments, and efficacy and prognostic factor data were evaluated. Survival analyses were performed using SPSS 15.0. Results: The median overall survival was 30.7 months (95% confidence interval [CI], 18.4-42.9 months). Median survival was 19 months (95% CI, 6-33) for patients treated with fluorouracil based chemotherapy and 53 months (95% CI, 33.2-78.8) with gemcitabine based chemotherapy(p=0.033). On univariate analysis, poor prognostic factors for survival were galbladder localization, perineural invasion, hepatic invasion, a lack of adjuvant chemoradiotherapy treatment, and a lack of lymph node dissection. On multivariate analysis, perineural invasion was a poor prognostic factor (p=0.008). Conclusions: Biliary tract cancers generally have poor prognoses. The main factors affecting survival are tumour localization, perineural invasion, hepatic invasion, adjuvant chemoradiotherapy, and lymph node dissection. Gemcitabine-based adjuvant chemotherapy is more effective than 5-fluorouracil-based chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5263-5267
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• 2013

Background: The aim of this study was to evaluate the efficacy and tolerability of a gemcitabine, 5-fluorouracil and leucovorin (GEMFUFOL) chemotherapy regimen as first line treatment of metastatic biliary tract cancer. Materials and Methods: All patients received folinic acid $400mg/m^2$ on day 1, 5-fluorouracil bolus $400mg/m^2$ on day 1, IV infusion of 5-fluorouracil $2400mg/m^2$ over 46 hours, and gemcitabine $1250mg/m^2$ on day 1. Results: A total of 29 patients with metastatic biliary tract cancer received GEMFUFOL regimen as the firstline treatment. The mean follow-up was 22.1 months (95%CI, 12.5-31.8). One patient (3.4%) achieved complete response, 5 (17.2%) had partial response, and 4 (13.8%) had stable disease. The median progression-free survival was 3.3 months (95%CI, 2.9-3.7), and the median overall survival was 8.8 months (95%CI, 3.5-14). The 1-year and 2-year survival rates were 58.6% and 30%, respectively. Grade 3 and 4 toxicity included neutropenia in 4 patients (13.7%), thrombocytopenia in 2 (6.8%), anemia2 (6.8%), and alopecia in 1 (3.4%). Two patients (6.8%) developed febrile neutropenia. A dose reduction was achieved in 8 patients (27.6%) while 5 patients had extended-interval dosage (17.2%) for toxicity. Conclusions: The GEMFUFOL chemotherapy regimen was generally efficacious and tolerable as a first-line treatment of metastatic biliary tract cancer.

• Genomics & Informatics
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• 제16권4호
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• pp.35.1-35.3
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• 2018

Biliary tract cancer (BTC) is a rare cancer and is associated with a poor prognosis. To understand the genetic characteristics of BTC, we analyzed whole-exome sequencing data and identified somatic mutations in patients with BTC. Tumors and matched blood or normal samples were obtained from seven patients with cholangiocarcinoma who underwent surgical resection. We discovered inactivating mutations of tumor suppressor genes, including APC, TP53, and ARID1A, in three patients. Activating mutations of KRAS and NRAS were also identified. Our analyses identified somatic mutations in Korean patients with BTC.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.674-681
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• 2023

Bile pigment, bilirubin, and biliverdin concentrations may change as a results of biliary tract cancer (BTC) altering the mechanisms of radical oxidation and heme breakdown. We explored whether changes in bile pigment components could help distinguish BTC from benign biliary illness by evaluating alterations in patients with BTC. We collected bile fluid from 15 patients with a common bile duct stone (CBD group) and 63 individuals with BTC (BTC group). We examined the bile fluid's bilirubin, biliverdin reductase (BVR), heme oxygenase (HO-1), and bacterial taxonomic abundance. Serum bilirubin levels had no impact on the amounts of bile HO-1, BVR, or bilirubin. In comparison to the control group, the BTC group had considerably higher amounts of HO-1, BVR, and bilirubin in the bile. The areas under the curve for the receiver operating characteristic curve analyses of the BVR and HO-1 were 0.832 (p<0.001) and 0.891 (p<0.001), respectively. Firmicutes was the most prevalent phylum in both CBD and BTC, according to a taxonomic abundance analysis, however the Firmicutes/Bacteroidetes ratio was substantially greater in the BTC group than in the CBD group. The findings of this study showed that, regardless of the existence of obstructive jaundice, biliary carcinogenesis impacts heme degradation and bile pigmentation, and that the bile pigment components HO-1, BVR, and bilirubin in bile fluid have a diagnostic significance in BTC. In tissue biopsies for the diagnosis of BTC, particularly for distinguishing BTC from benign biliary strictures, bile pigment components can be used as additional biomarkers.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6025-6027
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• 2014

Background: Because of the relative rarity of biliary tract cancers (BTCs), defining long term survival results is difficult. In the present study, we aimed to evaluate the survival of a series of cases in Turkey. Materials and Methods: A totally of 47 patients with billiary tract cancer from Mersin Goverment Hospital, Acibadem Kayseri Hospital and Kayseri Training and Research Hospital were analyzed retrospectively using hospital records between 2006-2012. Results: The median overall survival was $19.3{\pm}3.9$ months for all patients. The median disease free and overall survivals were $24.3{\pm}5.3$ and $44.1{\pm}12.9$ months in patients in which radical surgery was performed, but in those with with inoperable disease they were only $5.3{\pm}1.5$ and $10.7{\pm}3.2$ months, respectively. Conclusions: BTCs have a poor prognosis. Surgery with a microscopic negative margin is still the only curative treatment.