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 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*

At present, the classification, nomenclature, and definition of carcinoma of the bile ducts are controversial. Moreover, there is no uniformity between China and aboard, which has brought confusion to clinical practice. It needs to clarify regarding tumor naming principles, anatomical location, tumor origin, pathological classification, biological characteristics, clinical manifestations, treatment methods, etc. Additionally, the WHO tumor classification, UICC staging, ICD disease classification, relevant Chinese regulations, EASL, AJCC staging, and NCCN guidelines were also needed to be referred. After investigating the above-mentioned latest authoritative literature, based on the existing problems, combined with clinical practice in China, the author reevaluated the definition, classification, and nomenclature of cholangiocarcinoma, and proposes updated suggestions. Hoping to standardize and unify clinical practice for classification and nomenclature of cholangiocarcinoma in China.
Bile Duct Neoplasms/pathology* ; Bile Ducts/pathology* ; Bile Ducts, Intrahepatic/pathology* ; China ; Cholangiocarcinoma/pathology* ; Humans ; Neoplasm Staging ; Prognosis

Objectives: To investigate the clinical value of adjuvant chemotherapy(ACT) in patients with intrahepatic cholangiocarcinoma(ICC) who underwent radical resection and to explore the optimal population that can benefit from ACT. Methods: A retrospective cohort study method was adopted. The clinical and pathological data of 685 patients with ICC who underwent curative intent resection in 10 Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected;There were 355 males and 330 females. The age(M(IQR)) was 58(14) years (range: 22 to 83 years). Propensity score matching(PSM) was applied to balance the differences between the adjuvant and non-adjuvant chemotherapy groups. Log-rank test was used to compare the prognosis of the two groups of patients. A Bayesian network recurrence-free survival(RFS) prediction model was constructed using the median RFS time (14 months) as the target variable, and the importance of the relevant prognostic factors was ranked according to the multistate Birnbaum importance calculation. A survival prognostic prediction table was established to analyze the population benefiting from adjuvant chemotherapy. Results: Among 685 patients,214 received ACT and 471 did not receive ACT. A total of 124 pairs of patients were included after PSM, and patients in the ACT group had better overall survival (OS) and RFS than those in the non-ACT group(OS: 32.2 months vs. 18.0 months,P=0.003;RFS:18.0 months vs. 10.0 months,P=0.001). The area under the curve of the Bayesian network RFS prediction model was 0.7124. The results of the prognostic factors in order of importance were microvascular invasion (0.158 2),perineural invasion (0.158 2),N stage (0.155 8),T stage (0.120 9), hepatic envelope invasion (0.090 3),adjuvant chemotherapy (0.072 1), tumor location (0.057 5), age (0.042 3), pathological differentiation (0.034 0), sex (0.029 3), alpha-fetoprotein (0.028 9) and preoperative jaundice (0.008 5). A survival prediction table based on the variables with importance greater than 0.1 (microvascular invasion,perineural invasion,N stage,T staging) and ACT showed that all patients benefited from ACT (increase in the probability of RFS≥14 months from 2.21% to 7.68%), with a more significant increase in the probability of RFS≥14 months after ACT in early-stage patients. Conclusion: ACT after radical resection in patients with ICC significantly prolongs the OS and RFS of patients, and the benefit of ACT is greater in early patients.
Bayes Theorem ; Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; Chemotherapy, Adjuvant ; Cholangiocarcinoma/surgery* ; Female ; Humans ; Male ; Prognosis ; Retrospective Studies

Objective: Constructing and validating a nomogram model for preoperative prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis to assist decision making during surgery. Methods: Retrospectively collecting the clinical and pathological data of 1 031 ICC patients who underwent partial hepatectomy at Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University,General Hospital of Eastern Theater Command,or Zhongda Hospital Southeast University from January 2003 to January 2014. There were 682 males and 349 females; mean age was 54.7 years(range:18 to 82 years). There were 562 patients who underwent lymph node dissection and 469 patients who did not. Among the patients in the dissection group,Lasso regression method was used to filtrate preoperative variables related to lymph node metastasis and establish a nomogram. Bootstrap method was used to internally validate the discrimination of the nomogram,and the accuracy of the nomogram was assessed by using calibration curves. Patients were divided into low-moderate and high-risk groups based on model prediction probability. Propensity score matching(PSM) was used to analyze the overall survival (OS) and recurrence-free survival (RFS) of patients with and without lymph node dissection in the two groups,and to judge the importance of lymph node dissection in the two groups. Results: Six factors related to ICC lymph node metastasis were determined by Lasso regression,including hepatitis B surface antigen,CA19-9,age,lymphadenopathy,carcinoembryo antigen and maximum tumor diameter. These factors were integrated into a nomogram to predict ICC lymph node metastasis. The aera under curve value was 0.764,and the C-index was 0.754. Stratified analysis showed that OS and RFS in the high-risk group of lymph node metastasis were significantly lower than those in the low-medium risk group(median OS:14.6 months vs. 27.0 months,P<0.01; median RFS:9.1 months vs. 15.5 months,P<0.01). In the high-risk group,the median OS was 16.7 months and 6.3 months(Log-rank test: P=0.187;Wilcoxon test:P=0.046),and the median RFS was 11.0 months and 4.8 months(P=0.403),respectively in the lymph node dissection group and undissected group after PSM. In the low-medium-risk group,the median OS was 22.7 months and 26.7 months(P=0.288),and the median RFS was 13.0 months and 14.5 months(P=0.306),respectively in the lymph node dissection group and undissected group after PSM. Conclusions: The nomogram could be used for preoperative prediction of lymph node metastasis and prognostic stratification in patients with ICC. For patients with high risk of lymph node metastasis predicted by the model,active dissection should be performed. For patients predicted to be at low-moderate risk,lymph node dissection might be optional in some specific cases.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; Cholangiocarcinoma/surgery* ; Female ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology* ; Lymphatic Metastasis ; Male ; Middle Aged ; Nomograms ; Prognosis ; Retrospective Studies

Objective: To investigate the association between prealbumin and the long-term prognosis of patients with hilar cholangiocarcinoma(HCCA) following radical surgery. Methods: The clinical data of 262 HCCA patients who underwent radical surgery admitted from January 2010 to January 2017 at the First Affiliated Hospital of Army Medical University were collected,retrospectively. There were 158 males and 104 females; aged (57.6±9.9)years old(range:32 to 78 years). According to the preoperative serum prealbumin level(170 mg/L),the patients were divided into low prealbumin group(n=143) and normal prealbumin group(n=119). Follow-up until September 2020,the main research indicator was overall survival(OS), and the secondary research indicator was recurrence-free survival(RFS). The measurement data conforming to the normal distribution adopted the t test,the measurement data not conforming to the normal distribution adopted the Mann-Whitney U test,and the count data adopted the χ² test. The Kaplan-Meier method was used to calculate the cumulative survival rate. The Log-rank test was used for univariate analysis of the cumulative survival rate. Variables with P<0.10 in univariate analysis were included in the Cox proportional hazards model for multivariate analysis. Results: The 1-, 3-, and 5-year OS rate of the 262 patients was 73.4%, 32.1%, and 24.0%, respectively, and the 1-, 3-, and 5-year RFS rate was 54.6%, 25.2%, and 16.2%, respectively. Median OS and RFS were 21 months and 12 months for patients with low prealbumin and 25 months and 19 months for patients with normal prealbumin. The OS rate and RFS rate of patients in the low prealbumin group were lower than those in the normal prealbumin group, and the difference was statistically significant (both P<0.05). The results of univariate analysis indicated that low prealbumin, CA19-9>150 U/L, tumor infiltration length>3 cm, preoperative jaundice, macrovascular invasion, microvascular invasion, lymph node metastasis, and poor differentiation maybe the risk factors of OS,and low prealbumin,tumor invasion length>3 cm,macrovascular invasion, microvascular invasion,lymph node metastasis,and poor differentiation maybe the risk factors of RFS for postoperative for radical resection in patients with HCCA (all P<0.10). Multivariate results suggested that low prealbumin,tumor invasion length>3 cm,microvascular invasion,lymph node metastasis,and poor differentiation were independent risk factors affecting OS and RFS in patients with HCCA after radical operation (all P<0.05). Conclusion: Preoperative prealbumin level can predict the long-term prognosis of patients with hilar cholangiocarcinoma following radical surgery.
Adult ; Aged ; Bile Duct Neoplasms/surgery* ; Cholangiocarcinoma/surgery* ; Female ; Humans ; Klatskin Tumor/surgery* ; Lymphatic Metastasis ; Male ; Middle Aged ; Prealbumin ; Prognosis ; Retrospective Studies

Bile Duct Neoplasms/pathology* ; Bile Ducts, Intrahepatic/pathology* ; Cholangiocarcinoma/pathology* ; Consensus ; Humans