Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignant tumor with poor prognosis, and lymph node metastasis constitutes one of the critical risk factors contributing to unfavorable patient outcomes. Lymph node dissection holds significant value in accurately staging ICC, guiding prognostic evaluation, and determining adjuvant therapeutic strategies. In recent years, both domestic and international scholars have conducted extensive research on lymph node metastasis and dissection in ICC. However, discrepancies persist among various research findings and consensus guidelines domestically and internationally regarding the understanding and recommendations for lymph node dissection in ICC. Furthermore, substantial variations exist in the extent of lymph node dissection, the minimum number of lymph nodes required for retrieval, and surgical dissection techniques, which have consequently led to divergent research conclusions. To standardize the clinical practice of lymph node dissection for ICC in China and enhance the level of ICC diagnosis and treatment, the Branch of Biliary Surgery, Chinese Society of Surgery, Chinese Medical Association and Working Group of Biliary Surgeons, Chinese College of Surgeons, Chinese Medical Doctor Association, convened relevant experts to develop this expert consensus. This consensus document has been formulated based on the latest evidence-based medical research and accumulated clinical experience.
Humans ; Cholangiocarcinoma/pathology* ; Lymph Node Excision ; Bile Duct Neoplasms/pathology* ; Lymphatic Metastasis ; Consensus ; Prognosis

OBJECTIVES: To develop and validate a preoperative clinical-radiomics model for predicting overall survival (OS) and disease-free survival (DFS) in patients with extrahepatic cholangiocarcinoma (eCCA) undergoing radical resection. METHODS: In this retrospective study, consecutive patients with pathologically-confirmed eCCA who underwent radical resection at our institution from 2015 to 2022 were included. The patients were divided into a training cohort and a validation cohort according to the chronological order of their CT examinations. Least absolute shrinkage and selection operator (LASSO)-Cox regression was employed to select predictive radiomic features and clinical variables. The selected features and variables were incorporated into a Cox regression model. Model performance for 1-year OS and DFS prediction was assessed using calibration curves, area under receiver operating characteristic curve (AUC), and concordance index (C-index). RESULTS: This study included 123 patients (mean age 64.0 ± 8.4 years, 85 males/38 females), with 86 in the training cohort and 37 in the validation cohort. The OS-predicting model included four clinical variables and four radiomic features. It achieved a training cohort AUC of 0.858 (C-index = 0.800) and a validation cohort AUC of 0.649 (C-index = 0.605). The DFS-predicting model included four clinical variables and four other radiomic features. It achieved a training cohort AUC of 0.830 (C-index = 0.760) and a validation cohort AUC of 0.717 (C-index = 0.616). CONCLUSIONS The preoperative clinical-radiomics models show promise as a tool for predicting 1-year OS and DFS in eCCA patients after radical surgery.
Humans ; Male ; Female ; Retrospective Studies ; Middle Aged ; Cholangiocarcinoma/mortality* ; Prognosis ; Bile Duct Neoplasms/mortality* ; Tomography, X-Ray Computed/methods* ; Aged ; Radiomics

Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.
Cholangiocarcinoma/drug therapy* ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Bile Duct Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Animals ; Signal Transduction/drug effects*

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder. Its occurrence secondary to hepatobiliary malignancies is even rarer, and without timely diagnosis and treatment, the mortality rate is extremely high. There is a need to raise awareness of this disease. This report describes a case of a 70-year-old female patient diagnosed with AHA 2 months after surgery for cholangiocarcinoma, admitted to the Second Affiliated Hospital of Bengbu Medical College in October 2022. The patient presented with subcutaneous hematoma in both lower limbs. Coagulation function tests showed a markedly prolonged activated partial thromboplastin time (APTT) of 74.5 seconds, with no correction in the APTT mixing test. Coagulation factor assays revealed a severely reduced coagulation factor VIII activity (FVIII:C) of 0.3%, and an inhibitor titer of 25.6 BU/mL was detected. After ruling out other potential causes, the patient was diagnosed with cholangiocarcinoma-associated AHA. With chemotherapy to control the primary tumor, alongside hemostatic and immunosuppressive therapy for inhibitor eradication, AHA was brought under control. The patient had no further coagulation abnormalities or bleeding, enabling timely and full-course chemotherapy for cholangiocarcinoma and significantly improving survival and quality of life. Therefore, in patients with malignancies who present with spontaneous bleeding or unusual bleeding following surgery, trauma, or invasive procedures, clinicians should be alert to the possibility of secondary AHA. Timely diagnosis and treatment can significantly improve prognosis.
Humans ; Cholangiocarcinoma/surgery* ; Female ; Hemophilia A/drug therapy* ; Aged ; Bile Duct Neoplasms/surgery* ; Factor VIII

What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define "related stricture" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.
Child ; Humans ; Cholangitis, Sclerosing/diagnosis* ; Constriction, Pathologic/complications* ; In Situ Hybridization, Fluorescence ; Cholangiocarcinoma/therapy* ; Liver Diseases/complications* ; Cholestasis ; Inflammatory Bowel Diseases/therapy* ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/therapy*

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignant tumor in the liver after hepatocellular carcinoma. Its incidence and mortality rates have increased worldwide in recent years. Surgical resection is the best treatment modality for ICC;however,the overall prognosis remains poor. Accurate evaluation of post operative prognosis allows personalized treatment and improved long-term outcomes of ICC. The American Joint Commission on Cancer TNM staging manual is the basis for the standardized diagnosis and treatment of ICC;however,the contents of stage T and stage N need to be improved. The nomogram model or scoring system established in the analysis of commonly used clinicopathological parameters can provide individualized prognostic evaluation and improve prediction accuracy;however,more studies are needed to validate the results before clinical use. Meanwhile,imaging features exhibit great potential to establish the post operative prognosis evaluation system for ICC. Molecular-based classification provides an accurate guarantee for prognostic assessment as well as selection of populations that are sensitive to targeted therapy or immunotherapy. Therefore,the establishment of a prognosis evaluation system,based on clinical and pathological characteristics and centered on the combination of multidisciplinary and multi-omics,will be conducive to improving the long-term outcomes of ICC after surgical resection in the context of big medical data.
Humans ; Bile Ducts, Intrahepatic/pathology* ; Cholangiocarcinoma/pathology* ; Prognosis ; Liver Neoplasms/surgery* ; Bile Duct Neoplasms/pathology*

Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications* ; Cholangiocarcinoma/pathology* ; Carcinoma, Squamous Cell ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/pathology*

Humans ; Carcinoma, Hepatocellular/surgery* ; Liver Neoplasms/pathology* ; Cholangiocarcinoma/pathology* ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/pathology*

Objective: To explore the value of preoperative peripheral blood inflammatory biomarkers for predicting the prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection. Methods: A total of 124 patients who underwent radical resection for ICC in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2018 were retrospectively analyzed. Receiver operating characteristic (ROC) curve was conducted to determine the best cut-off values of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), systemic immune inflammatory index (SII), and systemic inflammatory response index (SIRI). Univariate and multivariate analyses of prognostic factors were performed using Cox proportional hazards regression model. Based on the independent prognostic factors screened by multivariate Cox regression analysis, a nomogram model of overall survival prediction for ICC patients after radical resection was established. Results: Among the 124 patients, 87 patients died and 37 patients survived during the follow-up period. The median overall survival time of the whole patients was 21 months. ROC curve analysis showed that the areas under the curve (AUC) of NLR, PLR, LMR, SII and SIRI for predicting the overall survival of ICC patients after radical resection were 57.86%, 64.21%, 60.61%, 67.57% and 66.03%, respectively. Univariate Cox regression analysis showed that the inflammatory biomarkers of NLR, PLR, SII, and SIRI were associated with overall survival of ICC after radical resection (HR=1.787, 95%CI: 1.165-2.741; HR=1.181, 95% CI: 1.224-2.892; HR=2.412, 95% CI: 1.565-3.717; HR=1.648, 95% CI: 1.081-2.513). Multivariate Cox regression analysis showed that the inflammatory biomarker of SII was an independent prognostic factor of ICC after radical resection (HR=1.863, 95% CI: 1.161-2.989). According to the best cut-off value of SII to predict the overall survival of ICC patients after radical resection (709.86×10(9)/L), the patients were divided into low SII group (SII≤709.86×10(9)/L) and high SII group (SII>709.86×10(9)/L). In the high SII group, the proportions of NLR>3.31, PLR>3.31, SIRI>1.30×10(9)/L, carbohydrate antigen 19-9>39.0 U/ml, Child-Pugh liver function (grade B), hemi-hepatic/extended hepatectomy, combined perineural invasion, N1 stage and TNM stage (ⅢB) were higher than those in the low SII group (P<0.05). Based on the independent prognostic factors screened by multivariate Cox regression analysis, a nomogram model of overall survival prediction for ICC after radical resection was established, the C-index values of the training set and testing set were 0.774 and 0.737, respectively. Conclusions: Preoperative peripheral blood inflammatory marker SII is an independent risk factor for the prognosis of intrahepatic cholangiocarcinoma patients after radical resection. The nomogram model of overall survival prediction established that included SII has a good predictive ability and can be used to evaluate the prognosis of intrahepatic cholangiocarcinoma patients after radical resection.
Humans ; Prognosis ; Retrospective Studies ; Inflammation ; Cholangiocarcinoma/surgery* ; Lymphocytes ; Neutrophils ; Biomarkers ; Bile Duct Neoplasms/pathology* ; Bile Ducts, Intrahepatic/pathology*