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*

Drug-induced bile duct injury is a specific kind of drug-induced liver injury that has two main pathological types, namely ductopenia, or vanishing bile duct syndrome, and secondary sclerosing cholangitis. However, in recent years, the reports of new drugs that cause bile duct injury have been constantly increasing, and these drugs have different clinicopathological features and a novel pathogenesis. Therefore, this paper summarizes and analyzes the progress and challenges in the etiology, pathogenesis, diagnosis and treatment, and other aspects of drug-induced bile duct injury.
Humans ; Cholestasis/chemically induced* ; Cholangitis, Sclerosing/diagnosis* ; Chemical and Drug Induced Liver Injury/pathology* ; Bile Ducts/pathology*

Objective: To explore the predictive factors of concurrent bile duct injury following transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: A retrospective study was conducted on 483 HCC patients in relation to TACE postoperative complications. A total of 21 cases of bile duct injury were observed following the TACE procedure. Laboratory data, imaging data, and clinically relevant medical histories were recorded before and after one week following the TACE procedure and follow-up. The χ (2) test, or Fisher's exact probability method, was used for categorical variables. The mean of the two samples was compared using a paired t-test or Wilcoxon rank sum test. The comparison of multiple mean values was conducted using an analysis of variance. Results: Twenty-one cases with bile duct injury had intrahepatic bile duct dilatation, bile tumors, hilar biliary duct stenoses, and other manifestations. 14.3% (3/21) of patients showed linear high-density shadows along the bile duct on a plain CT scan, while 76.2% (16/21) of patients had ALP > 200 U/L one week following TACE procedure, and bile duct injury occurred in later follow-up. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) were significantly increased in all patients following TACE procedure (t = -2.721, P = 0.014; t = -2.674, P = 0.015; t = -3.079, P = 0.006; t = -3.377, P = 0.003, respectively). Conclusion: The deposition of iodized oil around the bile duct on plain CT scan presentation or the continuous increase of ALP (> 200 U/L) one week following TACE procedure has a certain predictive value for the later bile duct injury.
Humans ; Liver Neoplasms/therapy* ; Carcinoma, Hepatocellular/therapy* ; Retrospective Studies ; Chemoembolization, Therapeutic/methods* ; Bile Ducts

Hepatic parenchymal cells are a type of liver cells that performs important functions such as metabolism and detoxification. The contribution of hepatic parenchymal cells, bile duct cells, and hepatic stem/progenitor cells to new hepatic parenchymal cells in the process of liver injury repair has become a controversial issue due to their strong proliferation ability. Lineage tracing technology, which has emerged in the past decade as a new method for exploring the origin of cells, can trace specific type of cells and their daughter cells by labeling cells that express the specific gene and their progeny. The article reviews the current literature on the origin and contribution of hepatic parenchymal cells by this technique. About 98% of new hepatic parenchymal cells originate from the existing hepatic parenchymal cells during liver homeostasis and after acute injury. However, under conditions of severe liver injury, such as inhibition of hepatic parenchymal cell proliferation, bile duct cells (mainly liver stem/progenitor cells) become the predominant source of hepatic parenchymal cells, contributing a steady increased hepatocyte regeneration with the extension of time.
Hepatocytes/metabolism* ; Liver/metabolism* ; Bile Ducts ; Stem Cells ; Liver Regeneration/physiology* ; Cell Differentiation

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 examine the significance and prognostic value of the classification of hilar cholangiocarcinoma based on actual anatomical location. Methods: A retrospective study was conducted including 120 patients of hilar cholangiocarcinoma treated at the Second Affiliated Hospital,Zhejiang University School of Medicine and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2019 to December 2021. Patients with hilar cholangiocarcinoma were classified for seven types according to the site of tumor location. The clinicopathological and prognostic data of 120 patients were retrospectively analyzed(There were 57 males and 63 females,the age (M(IQR)) was 61(22)years(range:42 to 85 years)). All patients received radical resection without visible intraoperative tumor residue and negative bile duct resection margin according to intraoperative pathological biopsy. The classification variables were analyzed by Pearson χ² test or Fisher's exact probability test,one-way ANOVA or Kruskal-Wallis rank sum test.Kaplan-Meier method was used for survival analysis. Cox proportional risk model was used for prognostic factors. Results: The coincidence rate of preoperative surgical planning and actual operational styles was verified in 33 cases. Twenty-six cases were consistent,and 7 cases were inconsistent,with a coincidence rate of 78.8%. According to the actual anatomical location,patients in type of secondary branch experienced a significantly longer operation duration,a higher portal vein resection rate,margin positive rate and more advanced T stage(all P<0.05). The median overall survival time of the unilateral main trunck group was 27.0 months,and the bilateral group was 17.0 months. Survival analysis based on the tumor classification of the actual anatomical location showed that the unilateral or main trunck group predicted less aggressive clinical features and favorable outcomes(HR=1.931,95%CI:1.066 to 3.499,P<0.05). Multivariate analysis demonstrated that the actual anatomical location of the tumor type(HR=2.269,95%CI:1.333 to 3.861,P=0.003),combined liver resection(HR=0.464,95%CI:0.253 to 0.848,P=0.013) and N stage(HR=6.317,95%CI:3.083 to 12.944,P<0.01) were independent factors affecting the prognosis of patients. Conclusion: The classification based on the actual anatomy can be used as a promising scheme in refining patient stratification and predicting survival in hilar cholangiocarcinoma,and it can guide the selection of surgical methods,and predict operative safety and radical resection rate.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; China ; Cholangiocarcinoma/surgery* ; Female ; Humans ; Klatskin Tumor/surgery* ; Male ; Retrospective Studies

Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; CA-19-9 Antigen ; Cholangiocarcinoma/diagnosis* ; Female ; Humans ; Laparoscopy ; Lymphatic Metastasis ; Male ; Nomograms ; Prognosis ; Retrospective Studies

Objective To investigate the expression and the potential roles of long non-coding RNA(lncRNA)cancer susceptibility candidate 2(CASC2)and imprinted gene H19 in extrahepatic cholangiocarcinoma(ECC). Methods Four samples from patients with ECC were collected for high-throughput sequencing which was conducted to reveal the transcriptomic profiles of lncRNA CASC2 and H19.Bioinformatics tools were employed to predict the potential roles of the two genes.Another 22 ECC tissue samples and the cholangiocarcinoma cell lines(RBE,QBC939,HuH-28,and HuCCT1)with different degrees of differentiation were selected for validation.The para-carcinoma tissue and normal human intrahepatic biliary epithelial cell(HIBEC)were used as the control groups.The expression levels of lncRNA CASC2 and H19 in carcinoma tissue,para-carcinoma tissue,and cell lines were determined by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation analysis was carried out for the clinical indicators of patients with the expression levels of the target genes. Results The two target genes showed significantly different expression between carcinoma tissue and para-carcinoma tissue(all P<0.05).Specifically,CASC2 had higher expression level in the carcinoma tissue than in the para-carcinoma tissue(t=1.262,P=0.025),whereas the expression of H19 showed an opposite trend(t=1.285,P=0.005).The expression levels of CASC2 in QBC939(t=8.114,P=0.015)and HuH-28(t=9.202,P=0.012)cells were significantly higher than that in the control group.The expression levels of H19 were significantly lower in RBE(t=-10.244,P<0.001),QBC939(t=-10.476,P<0.001),HuH-28(t=-19.798,P<0.001),and HuCCT1(t=-16.193,P=0.004)cells than in the control group.Bioinformatics analysis showed that CASC2 was mainly involved in the metabolic process and H19 in the development of multicellular organisms.Both CASC2 and H19 were related to catalytic activity.The expression level of lncRNA CASC2 was correlated with pathological differentiation(χ ²=6.222,P=0.022)and lymph node metastasis(χ²=5.455,P=0.020),and that of lncRNA H19 with pathological differentiation(χ²=1.174,P=0.029)and tumor size(χ²=-0.507,P=0.037). Conclusions In the case of ECC,lncRNA CASC2 and H19 have transcription disorders.lncRNA CASC2 is generally up-regulated in the carcinoma tissue,while H19 is down-regulated.Both genes have the potential to become new molecular markers for ECC.
Bile Duct Neoplasms/genetics* ; Bile Ducts, Intrahepatic/metabolism* ; Cholangiocarcinoma/genetics* ; Gene Expression Regulation, Neoplastic ; Humans ; RNA, Long Noncoding/genetics* ; Tumor Suppressor Proteins/genetics*