Biliary tract cancers (BTCs) are aggressive epithelial malignancies that can arise at any point of the biliary tree. Albeit rare, their incidence and mortality rates have been rising steadily over the past 40 years, highlighting the need to improve current diagnostic and therapeutic strategies. BTCs show high inter- and intra-tumour heterogeneity both at the morphological and molecular level. Such complex heterogeneity poses a substantial obstacle to effective interventions. It is widely accepted that the observed heterogeneity may be the result of a complex interplay of different elements, including risk factors, distinct molecular alterations and multiple potential cells of origin. The use of genetic lineage tracing systems in experimental models has identified cholangiocytes, hepatocytes and/or progenitor-like cells as the cells of origin of BTCs. Genomic evidence in support of the distinct cell of origin hypotheses is growing. In this review, we focus on recent advances in the histopathological subtyping of BTCs, discuss current genomic evidence and outline lineage tracing studies that have contributed to the current knowledge surrounding the cell of origin of these tumours.

UNASSIGNED: Intrahepatic cholangiocarcinoma (iCCA) is usually a fatal malignancy with rising incidence globally. Surgical resection currently remains the only curative treatment. However, as only a minority of iCCA is amenable to resection, new therapeutic modalities are needed. Our aims were to systematically review and perform a meta-analysis on the existing literature regarding the use of ablative therapies for iCCA and to assess their efficacy as a treatment modality by calculating pooled survival results and investigate associations between prognostic factors and survival.
UNASSIGNED: A comprehensive search of the PubMed database for relevant articles was performed. Studies assessing survival in patients with iCCA undergoing ablation were included. Data were extracted on patient, tumour and treatment characteristics and survival. Random effects meta-analysis was used to pool the data. Galbraith plots were used to investigate heterogeneity; bubble plots were formulated using regression-based meta-analysis.
UNASSIGNED: A total of 10 studies were included in the final analysis, yielding an aggregate of 206 patients (69.5% males, median age: 51.2-72.5) and 320 tumours. Of all patients, 70.4% were recurrent cases of iCCA, and 29.6% were cases of primary iCCA. The median overall survival ranged from 8.7 to 52.4 months. Pooled 1-, 3- and 5-year survival rates were 76% (95% confidence interval: 68-83%), 33% (21-44%) and 16% (7-26%), respectively. No significant association was found between the median age, number of tumours or median tumour size and 1-year survival.
UNASSIGNED: Ablative therapies display promising potential as treatment modalities for iCCA. However, further research is necessary to validate these findings.