PURPOSE: Biliary cancer is a highly malignant neoplasm with poor prognosis and most patients need to undergo palliative chemotherapy, however major clinical problem associated with the use of chemotherapy is chemoresistance. So far, we aimed at investigating clinical implications of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) and Jagged1 as chemoresistance factors in biliary tract cancer. METHODS: We used 5 human biliary tract cancer cell lines (SNU-245, SNU-308, SNU-478, SNU-1079, and SNU-1196), and investigated the chemosensitivity of APEX1 and Jagged1 through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Western blot. Alternately, the 10 patients of advanced biliary cancer consist of 2 group according to the chemotherapy response examined by immunohistochemistry using APEX1 and Jagged1 antibody, and protein expression level was scored for staining intensity and percent positive cell. RESULTS: The result of MTT assay after APEX1 knockdown showed that strong coexpression of APEX1 and Jagged1 cell line (SNU-245, SNU-1079, and SNU-1196) showed a greater decrease in IC₅₀ of chemotherapeutic agent (5-fluorouracil, gemcitabine and cisplatin). The Western blot analysis of APEX1 and Jagged1 expression in biliary cancer cell lines after APEX1 knockdown definitively demonstrated decreased Jagged1 expression. The APEX1 and Jagged1expression level of immunohistochemistry represented that chemorefractory patients had higher than chemoresponsive patients. CONCLUSION: These results demonstrate that simultaneous high expression of APEX1 and Jagged1 is associated with chemoresistance in biliary cancer and suggest that is a potential therapeutic target for chemoresistance in advanced biliary cancer.
Biliary Tract Neoplasms* ; Biliary Tract* ; Blotting, Western ; Cell Line ; Cisplatin ; Drug Therapy ; Fluorouracil ; Humans ; Immunohistochemistry ; Prognosis

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
Biliary Tract Neoplasms ; Biliary Tract ; Cholangiocarcinoma ; Exome ; Genes, Tumor Suppressor ; Humans ; Prognosis

Multiple synchronous malignancies are defined as the occurrence of two or more primary malignant tumors whose pathogenetic processes are believed to be independent or unrelated. Multiple synchronous biliary carcinomas are not frequently reported. The diagnosis is often made as a result of incidental intraoperative discovery of a gallbladder mass during surgical treatment of extrahepatic cholangiocarcinoma. We experienced a case of synchronous double primary cancer of the gallbladder and distal common bile duct confirmed by pathologic evaluation, and report the case with a review of the clinical literature.
Biliary Tract* ; Cholangiocarcinoma ; Common Bile Duct ; Diagnosis ; Gallbladder ; Gallbladder Neoplasms

OBJECTIVETo assess the efficacy and safety of bilateral versus unilateral biliary drainage in malignant hilar obstruction.

METHODSTopically relevant studies,regardless of randomized or observational design, were searched for in PubMed, EmBase and the Cochrane Library database. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to compare the effect of the two treatments.

RESULTSThree randomized trials and 7 observational studies were included, involving 894 patients with malignant hilar obstruction. The meta-analysis assessment of primary outcomes showed that the stent patency rate was better in bilateral drainage than in unilateral drainage (Rr=2.03,95% CI [1.16-3.56], P=0.01), but there were no significant differences in successful drainage rate (Rr=1.07,95% CI [0.97-1.18], P=0.20) and patient survival rate (Rr=-0.16,95% CI [-0.40-0.08], P=0.20). In the analysis of secondary outcomes,there were also no significant differences in the technical success rate (Rr=1.05,95% CI [0.98-1.17], P=0.34),the early complication rate (Rr=1.15, 95% CI [0.75-1.76], P=0.52), late complication rate (Rr=1.09,95% CI [0.75-1.60], P=0.60) and 30-day mortality rate (Rr=0.68,95% CI [0.38-1.23], P=0.20).

CONCLUSIONAlthough the cumulative stent patency was better for the bilateral than the unilateral drainage approach, based on the available data, there is not enough data to support bilateral drainage for malignant hilar obstruction. Well-designed randomized controlled trials are necessary to confirm it.

Malignant biliary tract obstruction (MBTO) is caused by a group of neoplasms that compromise bile duct flow, and the clinical presentation includes obstructive jaundice. The optimal treatment depends on both the type of malignancy and the stage of disease. Surgical resection may be the first choice of treatment. However, an operation is often impossible because of locally advanced disease or a high metastatic potential at the time of diagnosis. Considering the unfavorable prognosis of unresectable MBTO, endobiliary radiofrequency ablation (EB-RFA) has emerged as a palliative therapeutic modality that directly ablates malignant tissue in the bile duct. To date, some reports have suggested that EB-RFA is possibly beneficial, but it remains unclear whether EB-RFA prolongs biliary stent patency or overall survival. Nevertheless, EB-RFA is regarded as a promising loco-regional therapy for MBTO. This review focuses on the clinical application of the technique and its appropriate use, along with the benefits afforded and the complications encountered.
Bile Ducts ; Biliary Tract ; Biliary Tract Neoplasms ; Catheter Ablation* ; Cholangiopancreatography, Endoscopic Retrograde ; Diagnosis ; Jaundice, Obstructive ; Pancreatic Neoplasms ; Prognosis ; Stents

BACKGROUND/AIM: There is little data on whether plastic stents with a larger diameter are patent for longer than small stents in patients with bile duct cancer. The aim of this study was to compare the stent survival between 7-French (Fr) and 10-Fr plastic stents and evaluate the factors affecting stent survival. METHODS: Patients with biliary obstruction due to biliary tract cancer were enrolled at Yonsei University Wonju College of Medicine from January 2010 to October 2014. RESULTS: A total of 215 patients (7-Fr:10-Fr = 89:126 patients) were retrospectively enrolled. The primary tumor sites were common bile duct (n = 111), hilar (n = 45), and ampulla of Vater (n = 59). Rates of stent migration and stent obstruction were not different between the two groups. The median duration of stent survival was 3.3 months in the 7-Fr group and 5.9 months in the 10-Fr group (p = 0.543). The diameter of the stent did not have an effect on stent survival (hazard ratio 1.11, 95% confidence interval 0.71-1.73, p = 0.649). CONCLUSIONS: 7-Fr and 10-Fr stents have similar rates of stent migration and stent obstruction. The stent survival of 7-Fr was not inferior to 10-Fr stents in the management of biliary tract cancer.
Ampulla of Vater ; Bile Duct Neoplasms ; Biliary Tract Neoplasms* ; Biliary Tract* ; Common Bile Duct ; Gangwon-do ; Humans ; Plastics* ; Retrospective Studies ; Stents*

PURPOSE: Gemcitabine plus cisplatin (GemCis) is the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC). In ABC-02 study, the BTC patients received up to 6-8 cycles of 3-weekly GemCis; however, those without progression often receive more than 6-8 cycles. The clinical benefit of maintenance treatment in patients without progression is uncertain. MATERIALS AND METHODS: Advanced BTC patients treated with GemCis between April 2010 and February 2015 at Asan Medical Center, Seoul, Korea, were retrospectively analysed. The patients without progression after 6-8 cycles were stratified according to further treatment i.e., with or without further cycles of GemCis (maintenance vs. observation groups). The primary endpoint was overall survival (OS) and progression-free survival (PFS). RESULTS: Among the 740 BTC patients in the initial screen, 231 cases (31.2%) were eligible for analysis (111 in the observation group, 120 in the maintenance group). The median OS from the GemCis initiation was 20.5 months (95% confidence interval [CI], 15.4 to 25.6) and 22.4 months (95% CI, 17.0 to 27.8) in the observation and maintenance groups, respectively (p=0.162). The median PFS was 10.4 months (95% CI, 7.0 to 13.8) and 13.2 months (95% CI, 11.3 to 15.2), respectively (p=0.320). CONCLUSION: sGemCis maintenance is not associated with an improved survival outcome.
Biliary Tract Neoplasms ; Biliary Tract ; Cholangiocarcinoma ; Chungcheongnam-do ; Cisplatin ; Disease-Free Survival ; Drug Therapy ; Humans ; Korea ; Retrospective Studies ; Seoul

PURPOSE: Gastrin and cholecystokinin (CCK) have been reported to play a role in the development and growth stimulation of gastrointestinal cancers including pancreatic cancer. METHODS: We investigated the effects of gastrin and CCK on the growth of pancreatic and biliary tract cancer cell lines established at the Cancer Research Institute of Seoul National University College of Medicine, using reverse transcription-polymerase chain reaction (RT-PCR) and slot blot hybridization, to examine the expressions of hormonal receptors in these cell lines. RESULTS: Of the six biliary tract, and five pancreatic, cancer cell lines, SNU-308 showed a growth stimulated effect due to gastrin-17, as did SNU-478 to both gastrin-17 and CCK-8. The trophic effect of these two hormones was completely blocked by specific antagonists (L-365, 260 for gastrin and L-364, 718 for CCK). The other cell lines did not respond to either the gastrin or the CCK. From the RT-PCR, the presence of the CCK-A receptor and the CCK-B/gastrin receptor mRNA was detected in all the biliary and pancreatic cancer cell lines. From the slot blot hybridization, although the cell lines that responded to the hormones showed high level of expression for receptor mRNA, so did some of those not responding to the hormones. CONCLUSION: This study suggests that gastrin and CCK exert a trophic action on some biliary tract cancers due to their specific receptors. However, further studies investigating the functional and structural variation among these receptors, in relation to their subtypes and mutation/polymorphism are requisite prior to their clinical usage for adjunctive hormonal or antihormonal therapy can be recommended.
Academies and Institutes ; Bile Duct Neoplasms ; Biliary Tract ; Biliary Tract Neoplasms ; Cell Line* ; Cholecystokinin* ; Gallbladder Neoplasms ; Gastrins* ; Gastrointestinal Neoplasms ; Growth and Development ; Pancreatic Neoplasms ; Receptor, Cholecystokinin A ; RNA, Messenger ; Seoul ; Sincalide

Hemobilia is a hemorrhage into the biliary tract and is a relatively rare cause of bleeding in the digestive tract. Gallbladder cancer is the most common tumor in the biliary tract. Gastrointestinal bleeding including hemobilia is reported in only 3% of cases of gallbladder cancer. Here, we report two rare cases of gallbladder cancer diagnosed by the detection of hemobilia. One case was an anemic patient with no abnormal endoscopic findings; capsule endoscopy showed blood in the duodenum and repeat gastroendoscopy revealed hemorrhage from the ampulla of Vater. The diagnosis of early gallbladder cancer was made and the patient underwent surgery and was followed-up. The other case presented with a symptom triad including hemobilia, and endoscopic retrograded cholangiopancreatography (ERCP) revealed hemobilia and a filling defect in the gallbladder. This patient also underwent radical cholecystectomy with the diagnosis of gallbladder cancer.
Ampulla of Vater ; Biliary Tract ; Capsule Endoscopy ; Cholecystectomy ; Duodenum ; Gallbladder ; Gallbladder Neoplasms ; Gastrointestinal Tract ; Hemobilia ; Hemorrhage ; Humans

PURPOSE: Carcinomas of the biliary tract are considerably rare conditions. In spite of recent progress in diagnosis and treatment, resectability remains low, and the prognosis is still discouraging. This review summarizes our 12-year experience with biliary tract cancers, with particular focus on the survival rates after operation and the prognostic factors that affected the survival of patients. METHODS: Between 1987 and 1998, 268 patients with biliary tract cancers were operated on at our institution. The clinical and the pathologic data were collected, and a survival analysis was performed. RESULTS: The tumor was located in the gallbladder in 90 patients, in the proximal bile duct in 74 patients, in the distal bile duct in 54 patients, and in the ampulla of Vater in 50 patients. One hundred ninety-seven patients underwent a radical resection (resection rate: 73.5%). A curative resection was achieved in 140 patients (curative resection rate: 71.1%). The overall operative mortality after resection was 3.0%. The cumulative survival rates at five years after resection were 61.1% for carcinomas of the gallbladder, 25.8% for proximal bile duct cancers, 28.9% for distal bile duct cancers, and 48.7% for ampulla of Vater cancers. The one-year survival rates for the non-resection group were 18.2% and 26.6% for gallbladder cancers and proximal bile duct cancers, respectively. The mean survival periods for unresectable distal bile duct cancers and ampullary cancers were 4.7 months and 8.3 months, respectively. Positive lymph-node metastasis was a statistically significant, poor prognostic factor. CONCLUSION: Long-term survivals can be expected by a radical surgery for patients with biliary tract cancers. Increasing the resection rate by performing an extended procedure is essential for the improvement of treatment outcomes.
Ampulla of Vater ; Bile Duct Neoplasms ; Bile Ducts ; Biliary Tract Neoplasms* ; Biliary Tract* ; Diagnosis ; Gallbladder ; Gallbladder Neoplasms ; Humans ; Mortality ; Neoplasm Metastasis ; Prognosis* ; Survival Rate