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Purpose: The aim of this study was to conduct a nationwide population-based study to estimate the incidence of primary sclerosing cholangitis in patients with ulcerative colitis (UC-PSC) and investigate healthcare use, medication use, surgery, cancer, and death as adverse clinical events of UC-PSC. Methods: We identified incident cases of UC with (UC-PSC) or without PSC (UC-alone) between 2008 and 2018 using health insurance claims data in Korea. Univariate (crude hazard ratio (HR)) and multivariate analyses were performed to compare the risk of adverse clinical events between groups. Results: A total of 14,406 patients with UC using population-based claims data were detected in the cohort. Overall, 3.38% (487/14,406) of patients developed UC-PSC. During a mean follow-up duration of approximately 5.92 years, the incidence of PSC in patients with UC was 185 per 100,000 person-years. The UC-PSC group showed statistically more frequent healthcare use (hospitalization and emergency department visits: HRs, 5.986 and 9.302, respectively; P <.001), higher immunomodulator and biologic use (azathioprine, infliximab, and adalimumab: HRs, 2.061, 3.457, and 3.170, respectively; P <.001), and higher surgery rate (operation for intestinal obstruction, and colectomy: HRs, 9.728 and 2.940, respectively; P <.001) than did the UC-alone group. The UC-PSC group also showed significantly higher colorectal cancer and biliary tract cancer (HRs, 2.799 and 36.343, respectively; P <.001) and mortality (HR, 4.257) rates than did the UC-alone group. Conclusion: Patients with UC-PSC have higher risks of colorectal cancer, biliary tract cancer, and death than do patients with UC-alone. Although considered a rare disease, managing this complex and costly disease requires recognition of the impact of increased burden on healthcare services. [ABSTRACT FROM AUTHOR]

Biliary tract cancer (BTC) are highly aggressive and fatal malignancies. As one of the leading cause of death in Republic of Korea, BTC amoung various malignancies has been one of major public health concerns in the country. Although BTCs, including intrahepatic, perihilar, and distal cholangiocarcinoma, are relatively low-incidence malignancies compared to other cancer, but they represent a major health problem in endemic areas like Korea and Asia contries; moreover, the incidence of intrahepatic cholangiocarcinoma is rising globally. Surgery is the only curative treatment. The optimal surgical approach depends on the anatomical site of the primary tumour, and the best outcomes are achieved through management by specialist multidisciplinary team. Unfortunately, most patients present with locally advanced or metastatic disease. Only up to 20% of patients are diagnosed in early-stage, suitable for the curative surgery. Despite the surgery performed with potentially-curative intent, recurrence rates are high, around 60-70% of patients expected to have disease recurrence. In this review, we present an update of the causes, diagnosis, and treatment with a focus on chemotherapy of BTC. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with advanced biliary tract cancer who have progressed on gemcitabine plus cisplatin is dismal. We aimed to investigate the efficacy and safety of second-line liposomal irinotecan plus fluorouracil and leucovorin in patients with metastatic biliary tract cancer that has progressed on gemcitabine plus cisplatin.Methods: This multicentre, open-label, randomised, phase 2b (NIFTY) study was done at five academic institutions in South Korea and included patients aged 19 years or older with histologically or cytologically confirmed metastatic biliary tract cancer that had progressed on first-line gemcitabine plus cisplatin and an Eastern Cooperative Oncology Group performance status of 0 or 1. By use of an interactive web-based response system integrated with an electronic data capture system, patients were randomly assigned (1:1) using permuted blocks (block size 4) to receive either intravenous liposomal irinotecan (70 mg/m2 for 90 min) plus intravenous leucovorin (400 mg/m2 for 30 min) and intravenous fluorouracil (2400 mg/m2 for 46 h) every 2 weeks or leucovorin and fluorouracil only every 2 weeks, and were stratified by primary tumour site, previous surgery with curative intent, and participating centre. Study treatment was continued until the patient had disease progression or unacceptable toxicities, or withdrew consent. The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival. The primary endpoint and safety were assessed in the full analysis set and the safety analysis set, respectively, both of which comprised all randomly assigned patients who received at least one dose of the study treatment. This trial is registered with ClinicalTrials.gov, NCT03524508, and enrolment is complete.Findings: Between Sept 5, 2018, and Feb 18, 2020, 193 patients were screened for eligibility, of whom 174 (88 in the liposomal irinotecan plus fluorouracil and leucovorin group and 86 in the fluorouracil plus leucovorin group) were enrolled and included in the full analysis and safety analysis sets. At a median follow-up of 11·8 months (IQR 7·7-18·7), the median BICR-assessed progression-free survival was significantly longer in the liposomal irinotecan plus fluorouracil and leucovorin group (7·1 months, 95% CI 3·6-8·8) than in the fluorouracil and leucovorin group (1·4 months, 1·2-1·5; hazard ratio 0·56, 95% CI 0·39-0·81; p=0·0019). The most common grade 3-4 adverse events were neutropenia (21 [24%] of 88 in the liposomal irinotecan plus fluorouracil and leucovorin group vs one [1%] of 86 in the fluorouracil and leucovorin group) and fatigue or asthenia (11 [13%] vs three [3%]). Serious adverse events occurred in 37 (42%) patients receiving liposomal irinotecan plus fluorouracil and leucovorin and 21 (24%) patients receiving fluorouracil and leucovorin. There were no treatment-related deaths.Interpretation: Adding liposomal irinotecan to fluorouracil and leucovorin significantly improved BICR-assessed progression-free survival in patients with advanced biliary tract cancer. Liposomal irinotecan plus fluorouracil and leucovorin could be considered a standard-of-care second-line therapy for advanced biliary tract cancer.Funding: Servier and HK inno.N Translation: For the Korean translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

It is unknown whether persistent metabolic syndrome (MetS) is associated with an increased risk of cholangiocarcinoma (CCA). Therefore, we investigated the risk of CCA according to changes in MetS status. This nationwide cohort study included 8,581,407 adults who underwent anthropometric measurements and laboratory tests in two consecutive national health screenings during 2009–2012 and observed the subjects until 2017. Individuals with cancer, or follow-up duration <1 year were excluded (n = 377,915). Subjects were classified into the MetS-free, MetS-developed, MetS-improved, and MetS-persistent groups. The outcome was the incidence of CCA, identified using the claims database. Multivariable Cox proportional hazards regression models were used. Among the 8,203,492 subjects (mean age 48.9 ± 12.8 years; 56.7% male), 7506 CCA patients were newly identified during a median follow-up of 5.1 years. The probability of CCA was consistently higher in the MetS-persistent group than in the MetS-free group (P < 0.001). MetS-persistent status was significantly associated with an increased risk of CCA compared with the MetS-free status (unadjusted hazard ratio [HR] 2.8, 95% confidence interval [CI] 2.66–2.95), even after adjusting for multiple covariates (adjusted HR 1.07, 95% CI 1.01–1.13). Improved or newly developed MetS was not associated with CCA risk in the fully adjusted model (aHR 1.02, 95% CI 0.94–1.10 and aHR 0.99, 95% CI 0.92–1.06, respectively). MetS was associated with an increased risk of CCA if it persisted for ≥2 years. Our finding suggests that MetS may be a potentially modifiable risk factor for CCA. • Metabolic syndrome (MetS) is associated with a high risk of cholangiocarcinoma (CCA) if it existed for ≥2 years. • Persistent MetS may be a risk factor for CCA. • Because MetS is modifiable, optimal management of MetS may reduce CCA risk. [ABSTRACT FROM AUTHOR]

Background and Aim: While recent evidences support endoscopic resection as curative in ampullary tumors with high‐grade intraepithelial neoplasia, only small case series have reported endoscopic management of early‐stage ampullary cancer; thus, radical surgery remains the only accepted treatment modality. We evaluated the long‐term outcomes of early ampullary adenocarcinoma administered endoscopic management. Methods: We retrospectively reviewed electronic medical records of 715 patients undergoing endoscopic papillectomy (EP) in a single tertiary medical center in Korea in 2004–2016. We included patients incidentally diagnosed with early‐stage adenocarcinoma (Tis and T1a, American Joint Committee on Cancer 8th edition) after EP and with >2 years of follow‐up data and analyzed their demographics, histopathologic data, and clinical outcomes. Results: Among 70 total patients in the EP‐alone (n = 42) and subsequent surgery (n = 28) groups, we observed no significant differences in demographics or tumor size (2.0 ± 0.6 vs 1.9 ± 0.5 cm, P = 0.532), histologic grade (P = 0.077), tumor extent (P = 1.000), lymphovascular invasion (2.4% vs 10.7%, P = 0.344), or complete resection rates (57.1% vs 57.1%, P = 1.000) between groups. Adenocarcinoma lesions were larger in the subsequent surgery group (0.7 ± 0.5 vs 1.1 ± 0.7 cm, P = 0.002). The EP‐alone group received more additional ablative treatment (42.9% vs 14.3%, P = 0.024). The 5‐year disease‐free and cancer‐free survival rates were 79.1% vs 87.4% (P = 0.111) and 93.5% versus 87.4% (P = 0.726), respectively, and did not differ significantly between groups. Conclusions: Endoscopic papillectomy followed by endoscopic surveillance showed long‐term outcomes comparable with surgical resection for early ampullary cancer and maybe curable alternative to surgery for incidentally found early‐stage ampullary cancer, especially in patients unfit for or refusing radical surgery. [ABSTRACT FROM AUTHOR]

Objectives: In Jang-jeom, a small village in Hamra-myeon, Iksan-si, Jeollabuk-do, South Korea, residents raised concerns about a suspected cancer cluster that they attributed to a fertilizer plant near the village. We aimed to investigate whether the cancer incidence in the village was higher than that in the general Korean population when the factory was in operation (2001–2017) and whether living in the village was associated with a higher risk of cancer. Methods: Using national population data and cancer registration data of South Korea, we estimated the standardized incidence ratios (SIRs) in the village to investigate whether more cancer cases occurred in the village compared to other regions. The SIRs were standardized by age groups of 5 years and sex. In order to investigate whether residence in the village increased the risk of cancer, a retrospective cohort was constructed using National Health Insurance Service (NHIS) databases. We estimated the cancer hazard ratios (HRs) using the Cox proportional hazard model, and defined the exposed area as the village of Jang-jeom, and the unexposed or control area as the village neighborhood in Hamra-myeon. We considered potential confounding variables such as age, sex, and income index in the models. Additionally, we measured polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific nitrosamines (TSNAs), suspected carcinogens that may have caused the cancer cluster, in samples collected from the plant and the village. Results: Twenty-three cancer cases occurred in Jang-jeom from 2001 to 2017. Between 2010 and 2016, the incidence rates of all cancers (SIR: 2.05, except thyroid cancer: 2.22), non-melanoma skin cancer (SIR: 21.14, female: 25.41), and gallbladder (GB) and biliary tract cancer in men (SIR: 16.01) in the village were higher than those in the national population in a way that was statistically significant. In our cohort analysis that included only Hamra-myeon residents who have lived there for more than 7 years, we found a statistically significant increase in the risk of all cancers (HR: 1.99, except thyroid cancer: 2.20), non-melanoma skin cancer (HR: 11.60), GB and biliary tract cancer (HR: 15.24), liver cancer (HR: 6.63), and gastric cancer (HR: 3.29) for Jang-jeom residents compared to other Hamra area residents. We identified PAHs and TSNAs in samples of deposited dust and residual fertilizer from the plant and TSNAs in dust samples from village houses. Conclusions: The results of the SIR calculation and cancer risk analyses of Jang-jeom village residents from the retrospective cohort design showed consistency in the effect size and direction, suggesting that there was a cancer cluster in Jang-jeom. This study would be a good precedent for cancer cluster investigation. [ABSTRACT FROM AUTHOR]

Background: Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)-a small-molecule targeted inhibitor of mutated IDH1-in patients with previously treated IDH1-mutant cholangiocarcinoma.Methods: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov, NCT02989857.Findings: Between Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6·9 months (IQR 2·8-10·9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2·7 months [95% CI 1·6-4·2] vs 1·4 months [1·4-1·6]; hazard ratio 0·37; 95% CI 0·25-0·54; one-sided p<0·0001). The most common grade 3 or worse adverse event in both treatment groups was ascites (four [7%] of 59 patients receiving placebo and nine [7%] of 121 patients receiving ivosidenib). Serious adverse events were reported in 36 (30%) of 121 patients receiving ivosidenib and 13 (22%) of 59 patients receiving placebo. There were no treatment-related deaths.Interpretation: Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma.Funding: Agios Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Background/Aims: There have been no nationwide studies to investigate the trends in incidence and 5-year survival rates of intra- and extrahepatic bile duct cancers and gallbladder cancer. Therefore, our study aimed to describe the incidence and 5-year survival rates of biliary tract cancers by subsites in South Korea. Methods: A total of 86,134 patients with biliary tract cancers were selected from the National Health Information Database. Age-standardized incidence rates and annual percentage changes were calculated. Lifetable methods and log-rank tests were used to determine the differences in survival rates. Cox-proportional hazard models were used to estimate the hazard ratio of the patients with biliary tract cancers. Results: The incidence rate of intrahepatic bile duct cancer decreased by 1.3% annually from 8.8 per 100,000 in 2006 to 7.8 per 100,000 in 2015. Extrahepatic bile duct cancer also showed a decreasing trend by 2.2% per year from 8.7 per 100,000 in 2006 to 6.7 per 100,000 in 2015. Gallbladder cancer showed the greatest decline, with an annual percentage change of 2.8% from 6.3 per 100,000 to 5.2 per 100,000 during the same period. The 5-year survival rates were 30.0% in gallbladder cancer, 27.8% in extrahepatic bile duct cancer, and 15.9% in intrahepatic bile duct cancer. Conclusions: The overall incidence rates of intrahepatic and extrahepatic bile duct cancer and gallbladder cancer decreased from 2006 to 2015. Among biliary tract cancers, intrahepatic bile duct cancers exhibited the highest incidence rate and the worst survival rate. [ABSTRACT FROM AUTHOR]

Purpose: Biliary tract cancer (BTC) is a heterogeneous group of diseases comprising intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer. Although gemcitabine plus cisplatin (GEMCIS) was established as the standard first-line chemotherapy based on the ABC-02 trial, more data are needed to define the clinical course of BTC and its prognostic factors with the standard GEMCIS treatment.Methods: Between April 2010 and June 2016, 740 patients with histologically documented cholangiocarcinoma and gallbladder cancer were treated with first-line GEMCIS in Asan Medical Center, Seoul, Korea.Results: In 389 patients with measurable disease (53%), the objective response rate was 13% (n = 50) and there was no significant difference between primary tumor sites (p = 0.45). With a median follow-up duration of 27.3 months (95% CI 24.2-30.5), the median PFS and OS were 5.2 months (95% CI 4.7-5.6) and 10.4 months (95% CI 9.6-11.2), respectively. In multivariate analysis, male gender (female versus male, hazard ratio [HR] 0.83), baseline CA 19-9 level (elevated versus normal, HR 1.31), initially metastatic disease (versus locally advanced disease, HR 1.92), poor performance status (2 versus 0-1, HR 1.45), and measurable disease by RECIST criteria (versus non-measurable, HR 1.40) were significantly associated with a poorer OS (all p < 0.05).Conclusions: Our retrospective analysis of a large number of patients in a real-world setting found comparable efficacy outcomes to the ABC-02 trial. The prognostic factors identified here may help to predict clinical outcomes and design future clinical trials for advanced BTC. [ABSTRACT FROM AUTHOR]

Purpose: There is no established standard treatment for patients with locally advanced biliary tract cancer (BTC). Methods: We analyzed the treatment results of locally advanced BTC from Jan 1995 to Dec 2010 at single institution of South Korea with retrospective study. One hundred and seventy-six patients were eligible to investigate the treatment response and toxicity. We treated these patients with 5-fluorouracil (5-FU)- or gemcitabine (GEM)-based concurrent chemoradiotherapy (CCRT) or best supportive care (BSC). The primary end point was overall survival. Results: Of these locally advanced BTC patients, 106 patients received CCRT and 70 patients were treated with BSC. The median overall survival was 42.57 weeks (95 % confidence interval [CI], 35.85-49.30) in CCRT group and 13.29 weeks (95 % CI 10.42-16.15) in BSC group ( P < 0.001). Nausea and anemia were the most common toxicities observed. Conclusions: Patients with locally advanced BTC who were treated with 5-FU-based or GEM-based CCRT seem to have a better survival than those who received BSC. The treatment-related toxicity was mild. GEM-based or 5-FU-based CCRT showed similar survival advantages. [ABSTRACT FROM AUTHOR]

Background/Aims Administrative database provides valuable information for large cohort studies, especially when tissue diagnosis is rather difficult such as the diagnosis for bile duct cancer (BDC). However, studies regarding accuracy of administrative database for BDC have not been reported. The aim of this study was to evaluate the diagnostic accuracy of administrative database for BDC by International Classification of Diseases (ICD)-10 codes in a tertiary institute. Methods Study and control groups were collected from 2003 to 2016 at Seoul National University Bundang Hospital. Cases of BDC were identified in the National Health Insurance Service (NHIS) database by ICD-10 code supported by V code. The control group was selected from cases without ICD-10 codes for BDC. A definite or possible diagnosis was defined according to pathologic reports. Medical records, images, and pathology reports were analyzed to evaluate ICD-10 codes for BDC. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for BDC were analyzed according to diagnostic criteria and cancer locations. Results A total of 1,707 patients with BDC and 1,707 controls were collected. Among those with BDC, 1,320 patients (77.4%) were diagnosed by definite criteria. Most (99.4%) of them had adenocarcinoma. Rate of definite diagnosis was the highest for ampulla of Vater (AOV, 88.9%), followed by that for extrahepatic (85.0%) and intrahepatic (68.4%) BDCs. False positive cases commonly had hepatocellular carcinomas. For overall diagnosis of BDC, sensitivity, specificity, PPV, and NPV were 99.94%, 98.33%, 98.30%, and 99.94%, respectively. Diagnostic accuracies were similar regardless of diagnostic criteria or tumor locations. Conclusions Administrative database for BDC identified by ICD-10 code and NHIS provided very useful information regarding tumor location in relation to AOV and histology of BDC. [ABSTRACT FROM AUTHOR]

Pembrolizumab, an anti-programmed cell death (PD)-1 monoclonal antibody, is an anticancer agent showing substantial benefit in lung cancer and melanoma treatment. Biliary tract cancer (BTC) has been shown to respond to pembrolizumab; however, no credible data of such treatment outcomes exist. Therefore, we assessed the clinical outcomes and safety of pembrolizumab in patients with gemcitabine/cisplatin-refractory BTC. In this multicenter study, we retrospectively analyzed 51 patients with programmed cell death 1-ligand 1 (PD-L1)-positive gemcitabine/cisplatin-refractory BTC treated with pembrolizumab in four tertiary hospitals in Korea. PD-L1 positivity was defined as the expression of PD-L1 in ≥1% of tumor cells based on immunohistochemical staining (22C3, SP263, and E1L3N assays). The median age of the patients was 66 (range, 43–83) years and 29 (56.9%) were male. Extrahepatic cholangiocarcinoma was the most common cancer type (n = 30, 58.8%). Partial response and stable disease were achieved in 5 (9.8%) and 13 (25.5%) patients, respectively. Median progression-free survival and overall survival were 2.1 (95% CI, 1.7–2.4) and 6.9 (95% CI, 5.4–8.3) months, respectively. Overall, 30 (58.8%) patients experienced treatment-related adverse events (AEs). Only four (7.8%) patients experienced grades 3 and 4 AEs. In PD-L1-positive gemcitabine/cisplatin-refractory BTC, pembrolizumab presented durable efficacy, with a 9.8% response rate and manageable toxicity. [ABSTRACT FROM AUTHOR]

We aimed to investigate the perioperative outcomes of robotic pancreaticoduodenectomy (RPD) by assessing a consecutive series of totally robotic procedures. B Method: b All consecutive patients who underwent RPD were included in the present analysis from Dec 2015 to Dec 2018. The most common diagnosis was ampullary cancer (n=17) followed by bile duct cancer. [Extracted from the article]

Background/Aims Gemcitabine plus cisplatin (GP) has been regarded as the standard treatment for unresectable or recurrent biliary tract cancer (BTC). Potential biomarkers for GP response include the activities of cytidine deaminase (CDA), human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase M1 (RRM1). Here, we investigated whether intratumoral expression of these proteins were associated with the efficacy of gemcitabine chemotherapy in treating BTC. Methods This study prospectively enrolled 34 patients who were diagnosed with unresectable or recurrent BTC and treated with GP between 2015 and 2018 at National Cancer Center, Korea. We used immunohistochemistry to assess the intratumoral expression levels of CDA, hENT1, dCK, and RRM1 and investigated their relationship with the patients' clinical outcomes. Results With a median follow-up of 19.2 months, the group with positive RRM1 showed significantly worse overall survival (OS) (median: 6.58 months vs 9.78 months, p=0.039). RRM1 expression was significantly associated with progression-free survival (PFS) and OS in multivariate analysis adjusting for peritoneal metastasis and lung metastasis in multivariable analysis (PFS: hazard ratio [HR], 3.90; 95% confidence interval [CI], 1.41 to 10.79; p=0.009, OS: HR, 5.21; 95% CI, 1.88 to 14.42, p=0.002). However, immunohistochemistry (IHC) of other markers did not reveal any significant results. Conclusions Our finding suggests that IHC of intratumoral RRM1 might play an important role to predict the efficacy of GP in patients with advanced BTC. RRM1 needs further validation in the future. [ABSTRACT FROM AUTHOR]

There are huge unmet medical needs in biliary tract cancer. Biliary tract cancer is non-rare cancer in Asia especially in Korea. As a 1st-line chemotherapy, gemcitabine/cisplatin is current standard of care, and in 2nd-line setting, FOLFOX improved overall survival compared with best supportive care. Biliary tract cancer is a heterogenous group not only in primary origin but also molecular characteristics. Somatic alterations in the KRAS, TP53, CDKN2A, SMAD4, BAP1, ARID1A, PBRM1 and IDH1/2 have been reported. In recent study, 38.9% of biliary tract cancer cases harbor potentially targetable genetic alteration including FGFR1, FGFR2, FGFR3, PIK3CA, ALK, EGFR, ERBB2, BRAF, AKTS, IDH1, IDH2, CCND1, CCND3, MDM2, BRCA1 and BRCA. Targeting those molecular alterations are now being tried in clinical trials. Among them, targeting FGFR alteration especially FGFR2 fusion is far advanced in its clinical development, which is being followed by targeting mutant IDH1. This is era of immunotherapy in cancers. Mutant IDH inhibits HNF-4a to block hepatocyte differentiation and promote biliary cancer. A vaccine targeting mutant IDH1 induces antitumor immunity. Cholangiocarcinoma which harbor neoantigen by oncogene mutation could be candidate for adoptive transfer for TIL containing mutation-specific T cell. Anti-PD1 or PDL1 antibody has shown the promising antitumor efficacy in biliary tract cancer. PD1/PDL1 inhibitor with CTLA4 inhibitor or chemotherapy in combination with PD1/PDL1 inhibitor are under investigation. New drug development strategy including targeted agents and immuno-oncology might be enormously tested in biliary tract cancer. The integration of precision medicine might be one of key factors for the success of new drug development including targeted agents and immuno-oncology agents. [ABSTRACT FROM AUTHOR]