Association of glucagon-like peptide 1 receptor and the aggressiveness of extrahepatic cholangiocarcinoma.

Extrahepatic cholangiocarcinoma (eCCA) predominantly affects elderly patients, yet robust evidence evaluating surgical effectiveness in this population remains limited. This study aimed to determine the independent survival benefit of surgical resection in elderly patients with eCCA using propensity score matching to minimize selection bias. Patients aged ≥ 65years with non-metastatic eCCA diagnosed between 2010 and 2017 were identified from the SEER database. One-to-one propensity score matching (caliper 0.05 SD) balanced baseline characteristics between surgical (n = 682) and non-surgical (n = 617) groups, yielding 184 matched pairs. Overall survival (OS) and cancer-specific survival (CSS) were compared using Kaplan-Meier analysis and multivariable Cox regression. In the matched cohort, surgical resection was associated with significantly improved survival for both endpoints. For OS: median survival was 29 vs 8months (HR = 0.336, 95% CI: 0.267-0.423, P < 0.001), with 5-year OS rates of 25.3% vs 4.6%. For CSS: median survival was 36 vs 8months (HR = 0.307, 95% CI: 0.237-0.396, P < 0.001), with 5-year CSS rates of 34.5% vs 7.4%. Surgical benefit remained consistent across all age strata (65-74y: HR = 0.32; 75-84y: HR = 0.29; ≥ 85y: HR = 0.34), with no age interaction (P = 0.89). Tumor stage modified treatment effect (P = 0.012), with greater benefit in T1-2 (HR = 0.27) than T3-4 disease (HR = 0.40), though both groups benefited significantly. Surgical resection was associated with substantial survival benefit in elderly patients with non-metastatic, resectable eCCA, with approximately 66% reduction in mortality risk persisting across all age groups including octogenarians. Chronological age alone should not preclude surgical evaluation; decisions should incorporate comprehensive geriatric assessment and tumor biology.

Background & ObjectivesBased on the TOPAZ-I study, durvalumab combined with gemcitabine and cisplatin (GemCis) is now supported as a standard of care treatment for cholangiocarcinoma. Patients with extrahepatic cholangiocarcinoma (eCCA) often have underlying autoimmune conditions (AICs) which could restrict immunotherapy use. Treatment patterns in patients with eCCA with AICs and non-autoimmune conditions (NAICs) are reported.MethodThis retrospective observational analysis of adult patients diagnosed with eCCA in the United States enrolled in the International Cholangiocarcinoma Patient Registry between 2019 and 2023, focused on those treated with durvalumab. The registry contains de-identified data from medical records obtained directly from consenting patients and caregivers. Patients were followed from index date (date of eCCA diagnosis) until the last activity in the database or death. Demographics, clinical characteristics, biomarkers, treatment patterns, and adverse events (AEs) are reported.ResultsOverall, 135 patients with eCCA were enrolled: 24 (17.8%) had 2:1 AICs and 111 (82.2%) had NAICs. Baseline demographics were comparable between groups: the median (quartile [Q]l-Q3) age at diagnosis was 63.0 (55.0-70.0) years, the mean number of comorbidities in the overall population was 10.1, and 50.4% of patients were female. PD-Ll positivity was noted in 12.6% of patients and HER2 positivity in 10.4%. Of 91 patients with eCCA who received first-line therapy, 34 (37.4%) received GemCis alone, 27 (29.7%) chemotherapy alone (non-GemCis +/- nab-paclitaxel), 9 (9.9%) GemCis plus nab-paclitaxel, 7 (7.7%) durvalumab plus GemCis, 7 (7.7%) durvalumab monotherapy or in combination, and 7 (7.7%) other regimens. Treatment patterns by autoimmune comorbidity status are also reported (Table). Overall, 129 patients (95.6%) had ≥1 AE; fatigue was the most common (71.1%).ConclusionMore patients with eCCA received a first-line durvalumab-based regimen post-March 2022 vs the full study period. The use of durvalumab as first-line treatment in this subgroup may suggest that AICs do not restrict its use.52 TableTreatment patterns in patients with eCCA by autoimmune comorbidity status and from post-March 2022*No. of patients (%)First-line therapy by autoimmune comorbidity status, full study periodDurvalumab + GemCisWith AICs (n = 18)<5 (<27.7)With NAICs (n = 73)6 (8.2)First-line therapy, post-March 2022Durvalumab + GemCis or durvalumab monotherapy or in combination with another chemotherapy regimen (n = 20)12 (60.0)GemCis alone (n = 20)7 (35.0)*Durvalumab received U.S. Food and Drug Administration approval in March 2022.AIC, autoimmune condition; eCCA, extrahepatic cholangiocarcinoma; GemCis, gemcitabine and cisplatin; NAIC, non-autoimmune condition

Background & ObjectivesBiliary tract cancer (BTC) prognosis remains poor. We aimed to delineate distinguishing factors of resectable versus unresectable BTC to inform earlier diagnosis.MethodThis retrospective, observational study analyzed US claims and EHR de-identified Optum® Market Clarity data to identify adult patients diagnosed with resectable or unresectable BTC from January 2016-September 2023. Baseline demographics and clinical characteristics were retrieved. Logistic regression and XGBoost modeling were used to identify factors associated with resectable and unresectable BTC at diagnosis. XGBoost model performance was evaluated using receiver operating characteristic area under the curve (AUC).ResultsA total of 4448 patients with BTC were included (resectable, n = 641; unresectable, n = 3807). Median age (68-years-old) and sex (female: ∼52%) were similar in resectable versus unresectable BTC. Intrahepatic cholangiocarcinoma was common in unresectable BTC (43.6%); ampulla of Vater (AoV) and gallbladder cancer (GBC) were more common in resectable versus unresectable BTC (AoV: 17.0% vs 9.0%; GBC: 28.6% vs 17.0%).Resectable BTC at diagnosis was associated with: primary tumor site of AoV, GBC, and extrahepatic cholangiocarcinoma (eCCA); primary biliary cholangitis (PBC); and outpatient visits for gallstones or bile duct obstruction/biliary tract disease (Table). Factors associated with unresectable BTC diagnosis included prior cancer of unknown primary, Crohn's disease, inpatient visits for hepatomegaly, and outpatient visits for abdominal pain. XGBoost results were consistent with these findings, revealing diabetes, cardiovascular disease, and obesity as additional factors associated with resectable BTC. Strong discrimination between resectable and unresectable BTC at diagnosis (AUC, 0.93 [95% CI, 0.92--0.95]) was achieved with a sensitivity of 0.93 (95% CI, 0.91--0.94) in the test set.ConclusionFactors such as AoV and eCCA, which may enable earlier detection, were associated with resectable BTC, as well as PBC, diabetes, and gallstones, warranting a low threshold for screening in the setting of abnormal liver tests or suggestive symptoms.48 TableAssociated resectable or unresectable BTC characteristics.Clinical characteristicsOdds ratio* (95% CI)p-valueTumor site (reference: intrahepatic CCA)Ampulla of Vater2.65 (1.98-3.54)<0.001Gallbladder cancer2.59 (2.00-3.36)<0.001Extrahepatic CCA1.61 (1.21-2.16)0.001Prior cancer of unknown primary diagnosis (reference: no)0.27 (0.17-0.43)<0.001Comorbid conditions (reference: no)Primary biliary cholangitis3.34 (1.16-9.61)0.025Crohn's disease0.26 (0.08-0.87)0.029Primary diagnosis inpatient visits (reference: negative)Hepatomegaly0.51 (0.31-0.83)0.007Primary diagnosis outpatient visit (reference: negative)Calculus of gallbladder without cholecystitis without obstruction1.54 (1.13-2.11)0.007Abdominal pain0.71 (0.57-0.88)0.002Bile duct obstruction/biliary tract disease1.44 (1.13-1.83)0.003*Odds ratio > 1 favors resectable BTC; odds ratio <1 favors unresectable BTC.BTC, biliary tract cancer; CCA, cholangiocarcinoma; CI, confidence interval.

BackgroundBiliary tract cancer (BTC) has a poor prognosis with limited therapeutic options. γδ T cells represent an MHC-independent immune cell population; however, their therapeutic efficacy in solid tumours is constrained by insufficient tumour infiltration. Chemokine- mediated trafficking is fundamental to T lymphocyte recruitment; however, the chemokine landscape of the BTC tumour microenvironment (TME) remains uncharacterised.ObjectiveUsing single-cell RNA sequencing of BTC tissues, we delineated chemokine ligand expression patterns, stratified chemokine producers by lineage, assessed mechanisms of γδ T- cell recruitment, and identified chemokine-mediated immune escape.MethodsSingle-cell RNA-sequencing data from three GEO cohorts (GSE210066, GSE201425, GSE213452; 19 patients) encompassing intrahepatic, extrahepatic cholangiocarcinoma, and gallbladder malignancy were analysed using Seurat v5.0 in R. Quality control filtering applied stringent criteria (>200 genes, normal UMI counts, <15% mitochondrial content, <3% haemoglobin). Harmony batch correction across datasets preceded unsupervised clustering (resolution 0.9) and UMAP visualisation. Chemokine expression (17 ligands; 5 receptors) was systematically quantified across all cell types using average expression and percentage expression calculations.ResultsAnalysis of 119,840 quality-checked cells identified 26 distinct populations, including immune, epithelial, and stromal compartments. Comprehensive analysis identified a multi- axis chemokine profile, with high expression of CCL5 (30%), CXCL16 (24%), and CCL4 (23%) supporting γδ T-cell recruitment, while CCL2 and modest CXCL8 supported alternative Vδ1 T- cell axes. Notably, CXCL16 expression supported epithelial γδ T-cell homing via CXCR6. Paradoxically, chemokine axes supporting γδ T cell recruitment (CCL2-CCR2, CXCL8-CXCR1, CXCL12-CXCR4) simultaneously recruit immunosuppressive populations, such as myeloid- derived suppressor cells (MDSCs), regulatory T cells (Tregs), and tumour-associated macrophages (TAMs).ConclusionComprehensive single-cell analysis identified selective chemokine recruitment signatures supporting γδ T cell infiltration but revealed paradoxical co-recruitment of immunosuppressive populations in the BTC TME. Patient stratification via chemokine profiling combined with γδ T cell enrichment and targeted chemokine antagonism represents a rational therapeutic strategy.

BackgroundFollowing the positive results of TOPAZ-1 and KEYNOTE-966, gemcitabine plus cisplatin (GemCis) combined with durvalumab or pembrolizumab has been established as a global standard first-line regimen for advanced biliary tract cancer (BTC). Because patients treated in routine practice may differ from those enrolled in prospective trials, real-world evaluation of these regimens is warranted.MethodThe K-HBP Cancer Alliance comprises 11 tertiary referral hospitals in Korea. This multicenter retrospective study included patients who received first-line GemCis plus durvalumab or pembrolizumab for unresectable or metastatic BTC. Efficacy endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).ResultsBetween November 2022 and May 2025, 534 patients with BTC (211 [40%] intrahepatic cholangiocarcinoma [iCCA], 212 [40%] extrahepatic cholangiocarcinoma [eCCA], and 111 [20%] gallbladder cancer [GBC]) received GemCis plus durvalumab or pembrolizumab. Median age was 67 years (range, 29-89); 58% were male; 95% had ECOG performance status 0-1; and 81o/o had recurrent or metastatic disease. Median follow-up was 12.0 months (95% Cl, 10.3-13.5). ORR was 20% (95% Cl, 17-24%). Median PFS and OS were 6.6 months (95% Cl, 6.1-7.2) and 14.3 months (95% Cl, 12.9-15.8), respectively. One-year PFS and OS rates were 26% and 58%, respectively. Primary tumor site was not associated with PFS or OS. Elevated CA 19-9 (> median) was associated with inferior PFS (HR, 1.35; 95% Cl, 1.08-1.70; p = 0.009) and OS (HR, 1.53; 95% Cl, 1.13-2.03; p = 0.006).ConclusionIn this large multicenter real-world cohort, GemCis plus durvalumab or pembrolizumab demonstrated efficacy outcomes consistent with prospective trials.

Background and ObjectivesBiliary tract cancers (BTC) are an aggressive family of malignancies characterized by significant heterogeneity and poor patient outcomes. While numerous efforts have characterized BTCs genomically, few studies have focused on the RNA classification of primary BTCs at single-cell resolution. We will present our work to 1) identify conserved malignant cell RNA expression states, 2) define the role of non-malignant cells in supporting tumor growth and, 3) benchmark PDX model systems against their primary patient counterparts.MethodsWe performed probe-based single-cell RNA sequencing (scRNA-seq; 10X Genomics Flex) on a cohort of BTC resection specimens including intra- and extra-hepatic cholangiocarcinoma and gall bladder carcinoma. A subset of these samples had matched PDX models that were also analyzed with scRNA-seq.ResultsWe successfully captured a total of 232,631 patient cells across both malignant and non-malignant compartments. Using non-negative matrix factorization (NMF), we identified multiple conserved malignant cell RNA expression states, some of which were unique to specific disease subtypes (e.g., intra- versus extra-hepatic cholangiocarcinoma). Cross-correlation analysis comparing these single-cell programs to literature-curated gene sets demonstrated overlaps with major states described in prior bulk RNA-seq datasets but also revealed several new gene expression programs. We benchmarked PDX model systems against their corresponding patient tumors and observed variable preservation of clinical states in models.ConclusionsWe are continuing to interrogate this dataset to identify transcriptional programs associated with specific BTC genotypes. In future efforts, we plan to relate our dissociative scRNA-seq findings to spatial transcriptomic measurements across clinical BTC tissue microarrays. We anticipate that these high-resolution maps of BTC tumors and paired patient models will provide a blueprint for understanding how BTC transcriptional states shape malignant cell behaviors and will uncover new approaches to therapeutically target this challenging set of cancers.

The optimal surgical approach for middle-third extrahepatic cholangiocarcinoma (MCC)-bile duct segmental resection (BDSR) or pancreaticoduodenectomy (PD)-remains controversial. This study aimed to compare the short- and long-term outcomes of BDSR and PD in patients with MCC. We retrospectively analyzed 570 patients who underwent curative-intent surgery for MCC between January 2010 and December 2022. Clinicopathological characteristics, surgical outcomes, and oncologic outcomes (progression-free survival [PFS] and overall survival [OS]) were compared after 1:3 propensity score matching. Among 570 patients, 112 underwent BDSR and 458 PD. After propensity score matching, BDSR showed shorter operative time and hospital stay (both p < 0.001), but fewer retrieved lymph nodes and higher local recurrence rates (both p < 0.001). PFS was inferior after BDSR (27.4 vs. 34.3 months, p = 0.004), whereas OS was comparable (36.7 vs. 55.5 months, p = 0.117). In patients with R0 resection, both PFS and OS were similar between groups. BDSR may offer perioperative advantages over PD, but is associated with inferior PFS, with no significant difference in OS. In patients who achieved R0 resection, the PFS and OS did not reach statistical significance. This suggests that BDSR should be considered only in highly selected patients in whom R0 resection is achievable.

To investigate the diagnostic value of dual-time-point 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) in characterizing extrahepatic bile duct occupying lesions. A retrospective analysis was performed on 157 patients with suspected extrahepatic bile duct occupying lesions who underwent dual-time-point 18F-FDG PET/CT at the Affiliated Hospital of Chengde Medical University between January 2021 and February 2026. According to lesion nature, patients were divided into a malignant group and a benign group. The Mann-Whitney U test and χ2 test were used to compare clinical characteristics, laboratory indices, PET parameters, and diagnostic efficacy between groups. Multivariate logistic regression analysis was used to identify independent risk factors for diagnosing extrahepatic cholangiocarcinoma. A logistic regression model was established based on the selected variables, and receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic performance. A P value is less than 0.05 was considered statistically significant. Among the 157 patients with suspected extrahepatic bile duct occupying lesions, 126 cases (80.2%) were malignant and 31 cases (19.8%) were benign. Compared with the benign group, the malignant group showed statistically significant differences in jaundice (yes/no), intrahepatic bile duct dilatation (yes/no), extrahepatic bile duct dilatation (yes/no), CA19-9, retention index, maximum standard uptake value, early lesion-to-liver ratio (LLR), and delayed LLR (all P < 0.05). These variables were included in stepwise multivariate logistic regression to construct a regression equation. The area under the ROC curve was 0.912. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of dual-time-point 18F-FDG PET/CT for evaluating lesion nature were 95.10, 90.00, 85.10, 97.50, and 81.80%, respectively. Dual-time-point 18F-FDG PET/CT combined with CA19-9 and jaundice (yes/no) has important value in diagnosing the nature of extrahepatic bile duct occupying lesions.

MicroRNAs and predicted targets in the switch from monolayered to spheroids of cholangiocarcinoma cells.

Effect of Treatment Delay on Outcomes With Adjuvant Chemotherapy Versus Chemoradiotherapy in R1-Resected Biliary Tract Cancers.

ABSTRACTPurposeBiliary tract cancer (BTC) represents a heterogeneous disease with highly lethal malignancy and poor clinical outcomes. Here, we aimed to evaluate its genomic profiles to promote the development of precision medicine for BTC.Materials and MethodsGenomic analysis of 134 BTC patients was performed by using targeted panel sequencing in this study. The results of genomic testing were analyzed by integrating patients' clinicopathologic data, including treatment information and clinical outcomes. The significance of genetic alterations in our cohort was compared with western BTCs by using public repositories NGS data from ICGC cohort.ResultsThe most frequent genomic alterations were TP53 (55.5%), KRAS (38.1%), ARID1A (17.2%), and CDKN2A (15.7%) in our cohort. Notably, Chinese BTC patients had a higher prevalence of TP53, KRAS, and LRP1B alterations compared with Western BTCs. Moreover, a higher frequency of IDH and FGFR2 alterations was found in intrahepatic cholangiocarcinoma (ICA), whereas BRIP1, KRAS, and POLE alterations were more likely to accumulate in extrahepatic cholangiocarcinoma (ECA), and those with gallbladder carcinoma (GBC) had a higher prevalence of NF1, MSH3, and PIK3R1 alterations. Furthermore, several genomic alterations were observed to have a significant impact on progression‐free survival (PFS) and overall survival (OS) in our cohort. NGS data from the ICGC cohort further validated that TP53 was associated with inferior clinical outcomes both in Chinese and Western BTC patients, regardless of histopathologic subtypes or therapeutic approaches.ConclusionWe demonstrated the real‐world genomic characteristics of BTC patients, which may have promising implications for the development and application of precision medicine in the future. Well‐designed prospective studies are mandatory to validate the predictive role of significant genomic alterations observed in our study.

Immune cell infiltration patterns play important roles in shaping the tumor microenvironment of cholangiocarcinoma. However, efficient approaches for classifying these patterns from transcriptomic data remain limited. This study aimed to develop a machine learning-based framework to predict immune infiltration patterns in extrahepatic cholangiocarcinoma (EHCC). Transcriptomic data from the GSE132305 cohort were analyzed using CIBERSORT to estimate the proportions of 22 immune cell types. K-means clustering was applied to identify distinct immune infiltration patterns, with the optimal number of clusters determined by the silhouette method. Differentially expressed genes (DEGs) between clusters were identified using limma (|log2FC| > 2, adjusted p < 0.05). Functional enrichment analyses, including GO, KEGG, and GSEA, were performed to characterize biological differences between clusters. Hub genes were selected using five feature selection methods. Nine machine learning classifiers were then combined with these feature sets to construct 45 prediction models, which were evaluated using stratified five-fold cross-validation based on AUC, accuracy, sensitivity, and specificity. Two distinct immune infiltration patterns were identified among 182 EHCC samples, with significant differences in immune cell composition between Cluster 1 (n = 92) and Cluster 2 (n = 90). A total of 116 DEGs were identified between the two clusters. Functional enrichment analyses revealed marked differences in immune-related signaling and translational activity. Among the 45 models, the GBM-selected features combined with an SVM classifier achieved the best overall performance, with an AUC of 0.9958 and an accuracy of 96.7%. We developed a transcriptome-based machine learning framework for classifying immune infiltration patterns in EHCC. These findings improve the understanding of immune heterogeneity in EHCC and provide a computational basis for future validation in independent cohorts with clinical annotation.

Excessive accumulation of visceral adipose tissue (VAT), or obesity, has an association with cholangiocarcinoma prognosis. We hypothesized that qualitative assessment of VAT would have prognostic significance as well as quantitative assessment. The aim of this study was to measure 18F-fluorodeoxyglucose (18F-FDG) uptake in visceral fat by 18F-FDG positron emission tomography/computed tomography (18F-FDG-PET/CT) and to investigate the prognostic significance of the qualitative assessment of VAT. We retrospectively studied 103 patients with extrahepatic cholangiocarcinoma who underwent surgical resection from April 2017 to April 2023. 18F-FDG-PET/CT was performed before surgery, and the standardized uptake value (SUV) of VAT and blood pool were measured. The VAT-to-blood pool SUV ratio (VBR) was calculated as the ratio of VAT-SUV to blood pool SUV. The optimal VBR cutoff value to predict overall survival (OS) was 0.360. Compared with the low VBR group, the high VBR group was significantly associated with lower body mass index, skeletal muscle index, visceral fat area, subcutaneous fat area, and liver SUV. In the multivariate analysis, patients with a high VBR had poorer OS compared with those with a low VBR. Moreover, the VBR was significantly higher in patients with vs without malnutrition by the GLIM criteria. The VBR showed the lowest Akaike information criteria statistic value among the assessed parameters, indicating that it had the best ability to predict OS. This study suggested that the VBR, determined by 18F-FDG-PET/CT, is associated with the malnutrition and poor OS after resection of extrahepatic cholangiocarcinoma.

Biliary tract cancers (BTCs) are a group of highly aggressive malignancies with limited therapeutic options. Gemcitabine plus cisplatin (GemCis) remains the standard first-line regimen; however, the efficacy of currently recommended second-line therapies remains unsatisfactory. Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 or its ligand (PD-1/PD-L1) have demonstrated antitumor activity in a subset of patients with BTC, while albumin-bound paclitaxel (nab-paclitaxel) has shown efficacy across multiple solid tumors. This study aimed to evaluate the real-world safety and efficacy of a second-line combination regimen comprising PD-1/PD-L1 inhibitors, nab-paclitaxel, and fluorouracil-based agents (capecitabine or S-1) in patients with advanced BTCs. This retrospective study included patients with advanced BTCs who received second-line therapy with a combination of PD-1/PD-L1 inhibitors, nab-paclitaxel, and fluorouracil-based agents (capecitabine or S-1) at the Second Affiliated Hospital of Nanchang University between January 2019 and May 2025. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and treatment-related adverse events (TRAEs) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and TRAEs. A total of 36 patients were enrolled, including 17 (47.2%) with gallbladder cancer, 17 (47.2%) with intrahepatic cholangiocarcinoma, and 2 (5.6%) with extrahepatic cholangiocarcinoma. According to RECIST version 1.1, no complete responses (CR) were observed; four patients (11.1%) achieved a partial response (PR), 19 (52.8%) had stable disease (SD), and 13 (36.1%) experienced progressive disease (PD), yielding an ORR of 11.1% and a disease control rate (DCR) of 63.9%. The median progression-free survival (PFS) was 6.8 months (95% confidence interval [CI]: 4.2-10.2), and the median overall survival (OS) was 10.8 months (95% CI: 7.2-16.2). No significant differences in PFS (6.8 vs. 7.9 months, P = 0.55) or OS (11.1 vs. 10.8 months, P = 0.68) were observed between patients who had received prior immunotherapy and those who had not. The most common grade 3-4 TRAEs were chemotherapy-related myelosuppression, decreased appetite, and elevated total bilirubin. One patient developed hand-foot syndrome, and another experienced immune-mediated pneumonitis. No treatment-related deaths were reported. The combination of PD-1/PD-L1 inhibitors, nab-paclitaxel, and fluorouracil-based agents (capecitabine or S-1) demonstrated manageable toxicity and modest clinical activity as a second-line therapy for advanced BTCs. This regimen may represent a feasible treatment option for patients who progress following first-line therapy. Moreover, continued administration of this immunotherapy-based combination beyond initial progression may confer survival benefits in select patients.

In recent years, significant progress has been made in the imaging, molecular characterization, and systemic treatment of extrahepatic cholangiocarcinoma (CCA). However, early-stage detection, accurate classification, and effective management of CCA possess challenges. Therefore, the EASL commissioned an expert panel to draft evidence-based recommendations on account of recent research advances and significant differences in CCA subtypes for the management of extrahepatic CCA, including distal and perihilar CCA, with particular attention to the integration of emerging molecular concepts and practical strategies that reflect an accurate classification system needed in real-world clinical situations for the diagnosis and treatment.

Extra-hepatic cholangiocarcinoma diagnosis: from classical pathological analysis to the emerging omics tests.

BackgroundBiliary tract carcinoma (BTC) is underreported. This study describes the clinical characteristics and survival outcomes of BTC patients at six institutions in Colombia.MethodsThis is an observational, retrospective, multicenter, and real-life study of BTC patients. Baseline demographics, clinical characteristics, and treatment patterns were collected. A Kaplan-Meier analysis was used to estimate overall survival (OS), event-free survival (EFS), and progression-free survival (PFS). Multivariable Cox proportional hazards regression analyses for OS were performed in the overall cohort and in patients who received first-line treatment.ResultsA total of 214 BTC patients were included of which 136 were women (63.6%). Gallbladder carcinoma accounted for n=102 (47.7%), extrahepatic cholangiocarcinoma for n=59 (27.5%), and intrahepatic cholangiocarcinoma for n=53 (24.8%). Radical surgery was performed in 127 (59.3%) patients, 34 (26.8%) of whom remained relapse-free. First-line treatment for advanced disease was given to 116 patients (54.2%). Gemcitabine alone or in combination was used in 102 (87.9%) patients. The median EFS and OS were 16.4 months (95%CI: 12.3-20.6) and 21.5 months (95%CI: 14.2-28.8), respectively. Among patients initially diagnosed with metastatic disease, the median OS was 7.9 months (95%CI: 6.9-8.9). In 55 patients treated with gemcitabine-cisplatin as first-line therapy, the median OS was 9.6 months (95%CI: 5.5-13.7). In multivariable analysis, Eastern Cooperative Oncology Group performance status ≥2 and CA 19-9 >100U/mL were independently associated with worse OS.ConclusionsIn Colombia, patients with BTC face a poor prognosis, even in the early stages. Survival with gemcitabine-cisplatin for advanced disease is lower than that reported in clinical trials. These real-world data inform expectations for physicians and patients in Colombia.

Biliary tract cancer (BTC), encompassing intrahepatic and extrahepatic cholangiocarcinoma as well as gallbladder cancer, represents a heterogeneous group of malignancies characterized by an aggressive clinical course and poor prognosis. Systemic chemotherapy with gemcitabine plus cisplatin has remained the standard first-line treatment for more than a decade because most patients are diagnosed at an advanced or unresectable stage, but the associated survival benefit is limited. Recent therapeutic advances have been driven by the integration of immunotherapy and molecularly targeted approaches. Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) have shown clinically meaningful activity, particularly in combination with cytotoxic chemotherapy, and are increasingly being incorporated into first-line treatment strategies for advanced BTC. Concurrently, comprehensive molecular profiling has revealed substantial genomic heterogeneity and identified actionable alterations, including fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and human epidermal growth factor receptor 2 (HER2) amplification, enabling the development of precision targeted therapies for selected patient populations. Despite these advances, the therapeutic responses to immunotherapy and targeted agents remain highly variable, and robust predictive biomarkers have yet to be established. Accordingly, optimizing patient selection by integrating molecular and immunologic characteristics has become a critical objective for improving clinical outcomes. This review provides an overview of the recent progress in immunotherapy and targeted therapy for BTC, focusing on pivotal clinical trials, therapeutic efficacy, current limitations, and future perspectives for personalized treatment strategies.

Differentiating between malignant and benign biliary strictures remains a clinical challenge because current diagnostic tools have limited sensitivity. The detection of tumour-related biomarkers directly in bile, which is in close contact with the lesion, may enhance diagnostic accuracy. This study aimed at evaluating the diagnostic and prognostic values of biliary concentrations of VEGF, PDGF-AA, IGF and MMPs in patients with extrahepatic cholangiocarcinoma (CCA), pancreatic ductal adenocarcinoma (PDAC), or benign obstruction. A total of 100 consecutive patients undergoing ERCP for obstructive jaundice were enrolled and categorised into benign (n = 48), CCA (n = 23) and PDAC (n = 29) groups. Bile samples collected during ERCP were analysed. The diagnostic and prognostic performance of several biomarkers was assessed and, when appropriate, their incremental diagnostic value was assessed in comparison with standard bile cytology. Biliary concentrations of VEGF, MMP-1, MMP-2, MMP-7 and MMP-9 were significantly higher in malignant cases than in benign cases. VEGF demonstrated the best diagnostic accuracy (AUROC 0.86, sensitivity 87%, specificity 81%). MMP-1 and MMP-7 also showed good diagnostic values (AUROCs 0.79 and 0.81 respectively). In the multivariate analysis, VEGF was independently associated with the diagnosis of malignancy and PDAC, whereas both VEGF and MMP-2 were independently associated with CCA diagnosis. Using a predefined cut-off, bile VEGF showed a higher sensitivity than bile cytology, and their combination markedly reduced false-negative results. Regarding prognosis, higher PDGF-AA levels were independently associated with better survival rates. Biliary VEGF is a strong independent biomarker for the diagnosis of malignant biliary obstruction, both in PDAC and CCA. MMP-2 was independently associated with CCA diagnosis. PDGF-AA is a promising prognostic biomarker for malignant biliary strictures. These findings support the clinical potential of bile-based biomarkers for improving the diagnosis and assessing the prognosis of malignant biliary strictures.