Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic approaches. We present a novel system to monitor CCA using exosomal circular RNA (circRNA) via serum and biliary liquid biopsies. A pilot cohort consisting of patients with CCA-induced biliary obstruction (CCA-BO, n = 5) and benign biliary obstruction (BBO, n = 5) was used to identify CCA-derived exosomal circRNAs through microarray analysis. This was followed by a discovery cohort (n = 20) to further reveal a CCA-specific circRNA complex (hsa-circ-0000367, hsa-circ-0021647, and hsa-circ-0000288) in both bile and serum exosomes. In vitro and in vivo studies revealed the three circRNAs as promoters of CCA invasiveness. Diagnostic and prognostic models were established and verified by two independent cohorts (training cohort, n = 184; validation cohort, n = 105). An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature (Bile-DS, AUROC = 0.947, RR = 6.05) and serum exosomal circRNA signature (Serum-DS, AUROC = 0.861, RR = 4.04) compared with conventional CA19-9 (AUROC = 0.759, RR = 2.08). A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score, verified with bile samples (Bile-ERS, C-index=0.783) and serum samples (Serum-ERS, C-index = 0.782). These models, combined with other prognostic factors revealed by COX-PH model, enabled the establishment of nomograms for recurrence monitoring of CCA. Our study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

BACKGROUND Biliary tract cancer (BTC) is a rare, aggressive malignancy with increasing incidence and poor prognosis. Identifying preoperative prognostic factors is crucial for effective risk-benefit assessments and patient stratification. The prognostic nutritional index (PNI), which reflects immune-inflammatory and nutritional status, has shown prognostic value in various cancers, but its significance in BTC remains unclear. AIM To assess the prognostic value of the preoperative PNI in BTC patients, with a focus on overall survival (OS) and disease-free survival (DFS). METHODS Comprehensive searches were conducted in the PubMed, EMBASE, and Web of Science databases from inception to April 2024. The primary outcomes of interest focused on the associations between the preoperative PNI and the prognosis of BTC patients, specifically OS and disease-free survival (DFS). Statistical analyses were conducted via STATA 17.0 software. RESULTS Seventeen studies encompassing 4645 patients met the inclusion criteria. Meta-analysis revealed that a low PNI was significantly associated with poorer OS [hazard ratio (HR) 1.91, 95%CI: 1.59-2.29; P < 0.001] and DFS (HR 1.93, 95%CI: 1.39-2.67; P < 0.001). Subgroup analyses revealed consistent results across BTC subtypes (cholangiocarcinoma and gallbladder cancer) and stages (resectable and advanced). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected. CONCLUSION This study demonstrated that a low preoperative PNI predicts poor OS and DFS in BTC patients, highlighting its potential as a valuable prognostic tool. Further prospective studies are needed to validate these findings and enhance BTC patient management.

Background: Diet and nutrition, as a modifiable risk factor, have been demonstrated to play a significant role in the etiology of biliary diseases, whereas few comprehensive studies have been able to evaluate the strength and quality of these evidence. This umbrella review aims to evaluate the evidence pertaining risk factors for biliary diseases in terms of diet and nutrition-related indicators. Methods: An umbrella review method was adopted: evidence from observational studies up to 22 November 2021 were identified using PubMed, Web of Science, the Cochrane database, as well as manual screening. Eligible systematic reviews and meta-analyses were screened according to inclusion and exclusion criteria. The inclusion criteria were: (1) meta analysis or systematic review; (2) The theme of the study is the relationship between diet or nutrition and biliary tract diseases; (3) Summarized and reported OR, RR or HR values and corresponding 95% CI; (4) No restrictions on the use of participants and languages; (5) Only extract the data of biliary tract diseases from multiple health outcomes; (6) Only the most recent studies on the same subject were included. This study had been registered at PROSPERO (CRD42021293908). For each eligible systematic review and meta-analysis, we extracted the data of general characteristics and the main findings. The methodological quality of the meta-analyses included in our study were assessed by AMSTAR2 and the quality of evidence was evaluated by the GRADE. Results: A total of 323 articles were searched, among which 24 articles with 83 unique outcomes were identified as eligible. 35 of these outcomes were downgraded in GRADE evaluation as they reported heterogeneity. In short, among 83 unique outcomes, 5 were rated as moderate, 16 as low, and the rest as very low. For the prevention of biliary tract diseases, emphasis should be placed on appropriately increasing the intake of fruits, vegetables, coffee and tea, and reducing the intake of alcohol, raw fish and foods with high nitrate. Meanwhile, weight, blood sugar and lipid levels should be controlled, and diabetes should be actively prevented and treated. Drinking is not recommended to prevent gallstones, although studies have shown that it may reduce the risk of cholecystolithiasis. Conclusions: Our study summarizes the current multifaceted evidence on the relationship between dietary and nutritional indicators and biliary diseases, but the quality of all evidence was not high. Evidence from additional high-quality prospective studies are needed in the future.

To assess the prognostic value of lymphovascular invasion (LVI) in Bismuth-Corlette type IV hilar cholangiocarcinoma (HC) patients. A retrospective analysis was performed on 142 consecutively recruited type IV HC patients undergoing radical resection with at least 5 years of follow-up. Survival analysis was performed by the Kaplan-Meier method, and the association between the clinicopathologic variables and survival was evaluated by log-rank test. Multivariate analysis was adopted to identify the independent prognostic factors for overall survival (OS) and disease-free survival (DFS). Multiple logistic regression analysis was performed to determine the association between LVI and potential variables. LVI was confirmed histopathologically in 29 (20.4%) patients. Multivariate analysis showed that positive resection margin (HR = 6.255, 95%CI: 3.485-11.229, P < 0.001), N1 stage (HR = 2.902, 95%CI: 1.132-7.439, P = 0.027), tumor size > 30 mm (HR = 1.942, 95%CI: 1.176-3.209, P = 0.010) and LVI positivity (HR = 2.799, 95%CI: 1.588-4.935, P < 0.001) were adverse prognostic factors for DFS. The independent risk factors for OS were positive resection margin (HR = 6.776, 95%CI: 3.988-11.479, P < 0.001), N1 stage (HR = 2.827, 95%CI: 1.243-6.429, P = 0.013), tumor size > 30 mm (HR = 1.739, 95%CI: 1.101-2.745, P = 0.018) and LVI positivity (HR = 2.908, 95%CI: 1.712-4.938, P < 0.001). LVI was associated with N1 stage and tumor size > 30 mm. Multiple logistic regression analysis indicated that N1 stage (HR = 3.312, 95%CI: 1.338-8.198, P = 0.026) and tumor size > 30 mm (HR = 3.258, 95%CI: 1.288-8.236, P = 0.013) were associated with LVI. LVI is associated with N1 stage and tumor size > 30 mm and adversely influences DFS and OS in type IV HC patients.