We aimed to systematically assess the value of radiomics/machine learning (ML) models for diagnosing microvascular invasion (MVI) in patients with cholangiocarcinoma (CCA) using various radiologic modalities.

A systematic search of was conducted on Web of Sciences, PubMed, Scopus, and Embase. All the studies that assessed the value of radiomics models or ML models along with the use of imaging features were included. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria and METhodological RadiomICs Score (METRICS) were used for quality assessment. Pooled estimates for the diagnostic performance of radiomics/ML models were calculated. I-squared was used to assess heterogeneity, and sensitivity and subgroup analyses were performed to find the sources of heterogeneity. Deeks' funnel plots were used to assess publication bias.

11 studies were included in the systematic review with only one study being about extrahepatic CCA. According to the METRICS, the mean score was 62.99 %. Meta-analyses were performed on intrahepatic CCA studies. The meta-analysis of the best ML models revealed an AUC of 0.93 in the training cohort and an AUC of 0.85 in the validation cohort. Regarding the best radiomics model, the AUC was 0.85 in the training cohort and 0.81 in the validation cohort.

Radiomics/ML models showed very good diagnostic performance regarding MVI diagnosis in patients with intrahepatic CCA and may provide a non-invasive method for this purpose. However, given the high heterogeneity and low number of the included studies, further multi-center studies with prospective design and robust external validation are essential.

Cholangiocarcinoma (CCA) represents a heterogenous set of malignancies arising from the biliary tract. Classification of CCA subdivides tumours into intrahepatic (iCCA) and extrahepatic (eCCA), with eCCA further categorised as perihilar (pCCA) and distal (dCCA) lesions. Tumour subtypes show distinct epidemiological, genetic and clinical characteristics. Global incidence and mortality are rising, with the highest rates seen in Asian populations compared to the West. There has been a divergence in recent mortality trends observed between CCA subtypes, with rising rates of iCCA seen compared with eCCA. There are several drivers for these differing trends, including specific risk factors, misclassification of CCA subtypes and variation in diagnosis and surveillance. Risk factors for CCA can be divided into hepatobiliary, extra-hepatic and environmental, with hepatobiliary diseases conferring the largest risk. Surgery represents the only curative treatment for CCA, but can only be offered to early-stage candidates who are otherwise fit; the majority of patients are therefore treated with chemotherapy and, recently, immunotherapy. Due to late-stage presentation of disease, prognosis is poor, with 5-year survival <20%.

Malignant biliary strictures (MBSs) pose diagnostic and therapeutic challenges due to the frequent indeterminate results after initial sampling. A next-generation sequencing (NGS) panel (BiliSeq) offers promise in MBS detection, but real-world performance remains uncertain. This study aimed to assess standard sampling techniques alone and with BiliSeq for malignancy detection in biliary strictures and to evaluate management changes based on NGS.

This retrospective cohort study included 77 patients with biliary strictures undergoing BiliSeq during ERCP. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated, and sensitivity was compared between tests by using the McNemar test. Clinical impact was defined by identifying MBS patients with negative cytology/pathology correctly identified by BiliSeq.

Among 77 patients (28 malignant, 49 benign) who underwent BiliSeq testing during ERCP, primary sclerosing cholangitis was present in 24 patients (31.2%). A mass was detected in 35.7% of MBS cases versus 6.1% of benign cases (P = .001). BiliSeq sensitivity for malignancy was 75% (95% CI, 55.1%-89.3%), surpassing the combination of cytology and biopsy (42.9%; 95% CI, 24.5%-62.8%; P = .03). Combining BiliSeq with cytology/biopsy improved sensitivity from 42.9% to 85.7% (P < .001). Among MBS patients with negative cytology/biopsy findings (n = 16), BiliSeq altered management in 75%.

NGS and pathologic evaluation enhanced MBS detection sensitivity, leading to management changes in 75% of cases when pathology test results were negative.

Cholangiocarcinoma is a malignant tumor that emerges in the intrahepatic or extrahepatic bile ducts. Doramectin (DOR), a third-generation derivative of avermectins (AVMs), is renowned for its low toxicity and high efficiency. However, no research has hitherto focused on the anti-cholangiocarcinoma effects of these drugs. In this study, we undertook a preliminary exploration of the mechanism through which DOR inhibits the viability of human cholangiocarcinoma cells (Mz-ChA-1) via transcriptome analysis and molecular validation at the cellular level. The results indicated that DOR could suppress the growth and proliferation of Mz-ChA-1 cells in a dose-dependent manner. Moreover, it significantly diminished their migration and invasion abilities. Cell cycle analysis disclosed arrest in the G1 phase, accompanied by an increase in p21 expression and a decrease in the levels of the cyclin E1 and CDK2 proteins. Additionally, DOR induced apoptosis via the ROS-triggered mitochondrial pathway. This was attested by an elevation in the BAX/BCL-2 ratio, the activation of caspase 3/7 and the cleavage of PARP1. These mechanistic insights underscore DOR's potential as a therapeutic agent against cholangiocarcinoma.

Cholangiocarcinoma is a rare and heterogeneous disease that often requires multimodal treatment. The role of liver transplantation in these tumors has been controversial due to historically poor prognosis and higher recurrence rates. However, in recent years, scientific evidence has challenged this notion. We report the case of a 49-year-old woman with locally advanced intrahepatic cholangiocarcinoma. The therapeutic approach for this patient was complex, involving locoregional and systemic therapies. Despite the tumor's characteristics, namely, large size, multifocality, and vascular involvement, the good response to the treatment allowed a liver transplant 57 months after diagnosis.

Biliary tract cancers (BTCs) are aggressive malignancies with a dismal prognosis that require intensive targeted therapy. Approximately 10 % of BTCs have PBRM1 mutations, which impede DNA damage repair pathways and make cancer cells more susceptible to DNA-damaging chemicals. This review focus on development of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeting delivery system to selectively deliver chemotherapy into PBRM1-deficient BTC cells. These nanoparticles improve therapy efficacy by increasing medication targeting and retention at tumour locations. In preclinical studies, pharmacokinetic profile of this nanoparticle was encouraging and supported its ability to achieve extended circulation time with high drug accumulation in tumor. The review also highlights potential of Pou3F3:I54N to expedite bioassays for patient selection in BTC targeted therapies.

Endoscopic radiofrequency ablation (RFA) is used for the treatment of unresectable malignant biliary obstruction (MBO). The postoperative adverse events associated with RFA treatment have gained importance.

To investigate the early adverse events and their risk factors associated with RFA for the treatment of MBO.

Observational retrospective study.

We collected data from patients diagnosed with MBO and treated with endoscopic RFA at our hospital between January 2010 and June 2022. Based on the collected data, the patients were divided into two groups: the adverse event group and the nonadverse event group. Early postoperative adverse events were recorded, and risk factors were assessed.

One hundred and twenty patients with MBO underwent endoscopic RFA, with 20 developing adverse events (16.6%; 20/120). Among these, 13 patients (10.8%) developed biliary infection after RFA treatment, while 7 (5.8%) developed acute pancreatitis, and no bleeding or perforation occurred. Type 2 diabetes mellitus, bile duct stricture length >2.5 cm, segmental RFA, and the proportion of patients receiving single stent drainage were all significantly greater in the adverse event group compared to the nonadverse event group (p < 0.05). The results of the logistic regression analysis showed that type 2 diabetes, segmental RFA, and single stent drainage were the three independent risk factors for getting a biliary infection after RFA therapy.

Unresectable MBO combined with type 2 diabetes mellitus, segmental RFA, and postoperative single stent drainage can be the risk factors for adverse events after RFA. More attention should be paid to patients with multiple risk factors and preventive measures should be taken.

Chronic liver disease is a known risk factor for cholangiocarcinoma (CCA), but the proportion of people with CCA who have concurrent chronic liver disease is unclear. We aimed to evaluate the prevalence of chronic liver diseases in people with CCA.

In this single-arm meta-analysis, we searched MEDLINE and EMBASE from inception to August 10, 2024, for articles in English containing data for CCA with and without chronic liver diseases. Data were pooled to obtain the prevalence of different chronic liver diseases, with further stratification by geographical location and tumor location.

In total, 118,068 individuals diagnosed with CCA were included, of whom 16,771 had chronic liver diseases. A pooled analysis of 109 studies determined that the prevalence of chronic liver disease was 25.23% (95% confidence interval [CI], 20.82%-30.23%; I2 = 99.0%), and 10.21% (7.75%-13.35%; I2 = 98.6%) of CCA patients had cirrhosis. Chronic liver diseases were associated more with intrahepatic CCAs, compared with extrahepatic CCAs (relative risk, 2.46; 95% CI, 2.37-2.55; P < .0001). This was observed across all etiologies of liver disease, except for primary sclerosing cholangitis, which was associated with extrahepatic CCAs (relative risk, 0.49; 95% CI, 0.43-0.57; P < .0001).

Around 1 in 4 people with CCA have chronic liver diseases, and 1 in 10 have cirrhosis.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and has a poor prognosis. Surgical resection is the standard of care for patients with resectable disease, representing 30-40% of cases. Increasingly, neoadjuvant systemic therapy is being utilized in patients due to high-risk anatomic or biologic considerations. However, data on the clinical effect of this approach are limited. We performed a cohort study to evaluate the effect of neoadjuvant therapy in patients with oncologically high-risk iCCA.

iCCA patients (n = 181) between the years 2014-2020 were reviewed for clinical, histopathologic, treatment, and outcome-related data. Tumor regression grade was scored per CAP criteria for gastrointestinal carcinomas.

47 iCCA patients received neoadjuvant therapy and 72 did not. Neoadjuvant treatment led to objective response and tumor regression by CAP score. After adjustment for age, clinical stage, and tumor size, the outcomes of patients who had neoadjuvant therapy followed by surgery were not significantly different from those patients who had surgery first.

In conclusion, neoadjuvant therapy in iCCA facilitated surgical care. The progression-free and overall survival for surgical patients with and without neoadjuvant therapy were not significantly different suggesting this approach needs further exploration as an effective treatment paradigm.

Systemic chemotherapy is the main treatment option for patients with advanced intrahepatic cholangiocarcinoma (iCCA), however, its efficacy is limited. Herein, we report a young patient with NRAS-mutated chemoresistant metastatic iCCA, who received second-line therapy with a combination of trametinib (MEK1/2 inhibitor), hydroxychloroquine (autophagy inhibitor), and bevacizumab (angiogenesis inhibitor). A significant response was achieved during therapy, resulting in a 25% decrease in the size of tumor lesions after 2 months of treatment and an improvement in the patient's condition. The duration of this response was 4 months, but the patient died 10 months after the initiation of this triple therapy. This case report and the analysis of other available studies warrant further investigations on combined MEK and autophagy inhibition in RAS-mutated tumors.

Advances in precision medicine have expanded access to targeted therapies and demand for molecular profiling of cholangiocarcinoma (CCA) patients in routine clinical practice. However, pathologists face challenges in establishing a definitive intrahepatic CCA (iCCA) diagnosis while preserving sufficient tissue for molecular profiling. Additionally, they frequently face challenges in optimal tissue handling to preserve nucleic acid integrity.

This article first identifies the challenges in establishing a definitive diagnosis of iCCA in a lesional liver biopsy while preserving sufficient tissue for molecular profiling. Then, the authors explore the clinical value of molecular profiling, the basic principles of single gene and next-generation sequencing (NGS) techniques, and the challenges in tissue sampling for genomic testing. They also propose an algorithm for best practice in tissue management for molecular profiling of CCA.

Several practical challenges face pathologists during tissue sampling and processing for molecular profiling. Optimized tissue processing, careful tissue handling, and selection of appropriate approaches to molecular testing are essential to ensure that the highest possible quality of diagnostic information is provided in the greatest proportion of cases.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.hpb.2024.04.011. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Isocitrate dehydrogenase (IDH)1/2 genomic alterations (GA) occur in 20% of intrahepatic cholangiocarcinoma (iCCA); however, the immunogenomic landscape of IDH1-/2-mutated iCCA is largely unknown.

Comprehensive genomic profiling (CGP) was performed on 3,067 cases of advanced iCCA. Tumor mutational burden (TMB), PD-L1 expression (Dako 22C3), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) as a surrogate marker for homologous recombination deficiency were examined. RNA sequencing of 73 patient samples was analyzed for differences in stromal/immune cell infiltration, immune marker expression, and T-cell inflammation. Tissue microarray arrays were subjected to multiplex immunohistochemistry and colocalization analysis in 100 surgical samples. Retrospective clinical data were collected for 501 patients with cholangiocarcinoma to examine median overall survival (mOS) in IDH1/2+ versus IDHwt.

Of 3,067 iCCA cases subjected to CGP, 426 (14%) were IDH1+ and 125 (4%) were IDH2+. IDH1 GA included R132C (69%) and R132L/G/S/H/F (16%/7%/4%/3%/<1%). IDH2 GA occurred at R172 (94.4%) and R140 (6.6%). No significant difference was seen in median gLOH between IDH1+ versus IDHwt iCCA (P = .37), although patterns of comutations differed. MSI-High (P = .009), TMB ≥10 mut/Mb (P < .0001), and PD-L1 positivity were lower in IDH1/2+ versus IDHwt iCCA. Resting natural killer cell population, CD70, and programmed cell death 1 expression were significantly higher in non-IDH1-mutated cases, whereas V-set domain containing T-cell activation inhibitor 1 (B7-H4) expression was significantly higher in IDH1+. No significant difference in mOS was observed between IDH1/2+ versus IDHwt patients.

Significant differences in GA and immune biomarkers are noted between IDH1/2+ and IDHwt iCCA. IDH1-/2-mutated tumors appear immunologically cold without gLOH. These immunogenomic data provide insight for precision targeting of iCCA with IDH alterations.

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

High-grade dysplasia (HGD) in the cystic duct is a rare epithelial lesion that may lead to biliary tract malignancy. Due to its association with aggressive multifocal cholangiocarcinoma, it is important to investigate for concurrent malignancy, remove all areas of HGD and monitor for recurrence or metastasis.We present a case of a woman in her 60s with cholecystitis who underwent a laparoscopic cholecystectomy. On histopathology, the patient was found to have incidental HGD involving the cystic duct margin. After ensuring the absence of concurrent malignancy on cross-sectional imaging, she underwent further resection until the margins were clear of dysplasia. In the absence of clear follow-up guidelines, the patient was closely monitored with outpatient scans for up to 5 years.

Cholangiocarcinoma (CCA) is an aggressive cancer arising from any part of the biliary system. Effective treatment of CCA remains limited, resulting in the poor overall prognosis of patients. The effective prognostic biomarkers for CCA remain lacking, and most are at the research level.

The incidences of CCAs, classification, genetic and molecular characteristics, and distinct clinical outcomes in each subtype are introduced. The prognostic markers currently used in clinical practice are reviewed. Studies of biomarkers in defining the aggressiveness of CCA, identifying patients with a potential tumor recurrence, and predicting the survival time, are reviewed. Emerging biomarkers discovered from advanced high throughput technology over the past 5 years are updated and summarized. Finally, in-depth and critical revision on the prognostic biomarkers for CCA reported from various sources of specimens, e.g. tissues, blood, bile, etc. are discussed. Conclusion: Many prognostic biomarkers for CCA have been proposed and hold promising clinical value. However, these markers are rarely used in the real clinical world due to several factors. Understanding the roles and importance of these prognostic markers may fundamentally impact the therapeutic management of CCA, and hopefully, improve the development of custom and patient-directed therapies for CCA.

Cholangiocarcinoma is a highly aggressive cancer of the biliary tract epithelium. This form of cancer is prevalent in Asia, and recent reports show that its incidence is relatively rare but increasing in the United States. Although risk factors for cholangiocarcinoma have yet to be elucidated, a growing body of literature suggests chronic infection of genetically susceptible individuals with the food-borne zoonotic trematodes Clonorchis sinensis (C sinensis) and Opisthorchis viverrini (O viverrini) may play a role.

Although most infected people remain asymptomatic, untreated indolent infections with C sinensis and O viverrini may persist in peripheral intrahepatic bile ducts for almost 30 years. During this period, the trematodes' feeding activities and their excretory-secretory products may damage the bile duct epithelium and promote local inflammation. These pathological processes could then provoke epithelial desquamation, adenomatous hyperplasia, goblet cell metaplasia, periductal fibrosis, and granuloma formation that are conducive to the initiation and progression of cholangiocarcinoma in genetically susceptible people. The International Agency for Research on Cancer has determined that there is sufficient evidence in humans for the carcinogenicity of chronic infections with C sinensis and O viverrini.

Timely serodiagnosis of indolent C sinensis and O viverrini infections is important as these parasites may be a risk factor for cholangiocarcinoma in veterans who served in Vietnam. About 774,000 living Americans served in Vietnam and there is an urgent need to develop sensitive and specific serologic assays to detect both acute and indolent infections. We posit that testing and treatment of high-risk populations could lead to earlier detection and treatment of cholangiocarcinoma, leading to improved overall survival.

Pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are very aggressive tumors with a high mortality rate. Pancreas and distal bile ducts share a common embryonic development. Hence, PDAC and dCCA exhibit similar histological features that make a differential diagnosis during routine diagnostic practice challenging. However, there are also significant differences, with potential clinical implications. Even if PDAC and dCCA are generally associated with poor survival, patients with dCCA seem to present a better prognosis. Moreover, although precision oncology-based approaches are still limited in both entities, their most important targets are different and include alterations affecting BRCA1/2 and related genes in PDAC, as well as HER2 amplification in dCCA. Along this line, microsatellite instability represents a potential contact point in terms of tailored treatments, but its prevalence is very low in both tumor types. This review aims at defining the most important similarities and differences in terms of clinicopathological and molecular features between these two entities, also discussing the main theranostic implications derived from this challenging differential diagnosis.

Cholangiocarcinomas are cancers arising from bile ducts, either found within the liver (intrahepatic) or outside the liver (extrahepatic). In Western countries, deaths due to intrahepatic cancers are rising at a higher rate than deaths due to extrahepatic cancers. This may be due to rising cases of liver disease and misclassification of the different cancer types.