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*

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

BACKGROUND/AIMS: Determining the cause of suspected biliary stricture is often challenging in clinical practice. We aimed to compare the diagnostic yields of endoscopic ultrasound-guided tissue sampling (EUS-TS) and endoscopic retrograde cholangiopancreatography-guided tissue sampling (ERCP-TS) in patients with suspected biliary stricture at different primary lesions. METHODS: We enrolled patients who underwent same-session EUS- and ERCP-TS for the evaluation of suspected biliary stricture. Forceps biopsy and/or brush cytology of intraductal lesions and fine-needle aspiration for solid mass lesions were performed during ERCP and EUS, respectively. RESULTS: One hundred and twenty-five patients treated at our institution between January 2011 and September 2016, were initially considered for the study. However, 32 patients were excluded due to loss of follow-up (n=8) and ERCP-TS on the pancreatic duct (n=20) or periampullary lesions (n=4). Of the 93 patients included, 86 had a malignant tumor including cholangiocarcinoma (n=39), pancreatic cancer (n=37), and other malignancies (n=10). Seven patients had benign lesions. EUS-TS had higher rate of overall diagnostic accuracy than ERCP-TS (82.8% vs. 60.2%, p=0.001), and this was especially true for patients with a pancreatic lesion (84.4% vs. 51.1%, p=0.003). CONCLUSIONS: EUS-TS was found to be superior to ERCP-TS for evaluating suspected biliary strictures, especially those caused by pancreatic lesions.
Biopsy ; Biopsy, Fine-Needle ; Cholangiocarcinoma ; Cholangiopancreatography, Endoscopic Retrograde ; Constriction, Pathologic ; Diagnosis ; Endosonography ; Follow-Up Studies ; Humans ; Pancreatic Ducts ; Pancreatic Neoplasms ; Surgical Instruments

The malignant degree of cholangiocarcinoma is high, and the early diagnosis is difficult. The vast majority of patients are unresectable when they are diagnosed. The patients have low quality of life and short survival cycle. Traditional radiotherapy and chemotherapy have poor efficacy and lead to side effects, and thus lack effective control measures for cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography (ERCP) is an important method for diagnosing and treating biliary tract diseases. Photodynamic therapy (PDT) is a new local treatment for cholangiocarcinoma. In recent years, ERCP-mediated PDT treatment of cholangiocarcinoma has gradually emerged. ERCP-mediated PDT can effectively relieve the symptoms of patients with cholangiocarcinoma, improve the patients' quality of life, prolong the survival cycle, and is expected to become a new treatment for cholangiocarcinoma.
Bile Duct Neoplasms ; diagnosis ; Bile Ducts, Intrahepatic ; Cholangiocarcinoma ; diagnosis ; Cholangiopancreatography, Endoscopic Retrograde ; Humans ; Photochemotherapy ; Quality of Life

Concurrent advancements in imaging and genomic biomarkers have created opportunities to identify non-invasive imaging surrogates of molecular phenotypes. In order to develop such imaging surrogates radiomics and radiogenomics/imaging genomics will be necessary; there has been consistent progress in these fields for primary liver cancers. In this article we evaluate the current status of the field specifically with regards to hepatocellular carcinoma and intrahepatic cholangiocarcinoma, highlighting some of the up and coming results that were presented at the annual Radiological Society of North America Conference in 2017. There are an increasing number of studies in this area with a bias towards quantitative feature measurement, which is expected to benefit reproducibility of the findings and portends well for the future development of biomarkers for diagnosis, prognosis, and treatment response assessment. We review some of the advancements and look forward to some of the exciting future applications that are anticipated as the field develops.
Bias (Epidemiology) ; Biomarkers ; Carcinoma, Hepatocellular ; Cholangiocarcinoma ; Diagnosis ; Genomics ; Liver Neoplasms ; Liver ; North America ; Phenotype ; Prognosis

The liver is one of the most common sites to which malignancies preferentially metastasize. Although a substantial number of liver malignancies are primary tumors, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, the metastasis of carcinomas to the liver is relatively common and frequently encountered in clinical settings. Representative carcinomas that frequently metastasize to the liver include colorectal carcinoma, breast carcinoma, neuroendocrine tumors, lung carcinoma, and gastric carcinoma. The diagnostic confirmation of suspected metastatic lesions in the liver is generally achieved through a histopathologic examination of biopsy tissues. Although morphology is the most important feature for a pathologic differential diagnosis of metastatic carcinomas, immunohistochemical studies facilitate the differentiation of metastatic carcinoma origins and subtypes. Useful immunohistochemical markers for the differential diagnosis of metastatic carcinomas in the liver include cytokeratins (CK7, CK19, and CK20), neuroendocrine markers (CD56, synaptophysin, and chromogranin A), and tissue-specific markers (CDX2, SATB2, TTF-1, GCDFP-15, mammaglobin, etc.). Here, we provide a brief review about the pathologic differential diagnosis of major metastatic carcinomas in the liver.
Biopsy ; Breast Neoplasms ; Carcinoma, Hepatocellular ; Cholangiocarcinoma ; Colorectal Neoplasms ; Diagnosis, Differential ; Immunohistochemistry ; Keratins ; Liver Neoplasms ; Liver ; Lung ; Neoplasm Metastasis ; Neuroendocrine Tumors ; Pathology ; Synaptophysin

BACKGROUND/AIMS: Pathological diagnosis of biliary strictures with atypical or suspicious cells on endoscopic retrograde brush cytology and indeterminate strictures on imaging is challenging. The aim of this study was to identify markers for malignant strictures in such cases. METHODS: We retrospectively analyzed data collected from 146 consecutive patients with indeterminate biliary strictures on imaging who underwent endoscopic retrograde brush cytology from 2007 to 2013. Factors associated with malignant strictures in patients with atypical or suspicious cells on brush cytology were identified. RESULTS: Among the 67 patients with a malignant disease (48 cholangiocarcinoma, 6 gallbladder cancer, 5 pancreatic cancer, 5 ampulla of Vater cancer, and 3 other types), 36 (53.7%) had atypical or suspicious cells on brush cytology. Among these, the factors that independently correlated with malignant strictures were stricture length (odds ratio [OR], 5.259; 95% confidence interval [CI], 1.802– 15.294) and elevated carbohydrate antigen 19-9 (CA19-9) (OR, 3.492; 95% CI, 1.242–9.815), carcinoembryonic antigen (CEA) (OR, 4.909; 95% CI, 1.694–14.224), alkaline phosphatase (ALP) (OR, 3.362; 95% CI, 1.207–9.361), and gamma-glutamyl transpeptidase (rGT) (OR, 4.318; 95% CI, 1.512–12.262). CONCLUSIONS: Elevated levels of CA19-9, CEA, ALP, and rGT and stricture length are associated with malignant strictures in patients with indeterminate biliary strictures on imaging and atypical or suspicious cells on brush cytology.
Alkaline Phosphatase ; Ampulla of Vater ; Carcinoembryonic Antigen ; Cholangiocarcinoma ; Constriction, Pathologic ; Diagnosis ; Gallbladder Neoplasms ; gamma-Glutamyltransferase ; Humans ; Pancreatic Neoplasms ; Retrospective Studies

BACKGROUND/AIMS: Recurrent pyogenic cholangitis (RPC) is a chronic progressive disease frequently accompanied by cholangiocarcinoma (CCA). This study aimed to investigate the natural course of RPC and identify factors associated with CCA. METHODS: From January 2005 to December 2016, 310 patients diagnosed with RPC at Seoul National University Hospital were included. Complications and management during follow-up were recorded. CCA-free probability was estimated by Kaplan-Meier method, and risk factors associated with CCA were analyzed using log-rank test and Cox’s proportional hazard regression model. RESULTS: Mean age at diagnosis was 59.1±10.9 years and mean follow-up duration was 84.0±64.1 months. An intrahepatic duct stone was found in 253 patients (81.6%). Liver atrophy was identified in 185 patients (59.7%) and most commonly located at the left lobe (65.4%). Acute cholangitis, liver abscesses, cirrhotic complications, and CCA developed in 41.3%, 19.4%, 9.7%, and 7.4%, respectively. During follow-up, complete resolution rate after hepatectomy, biliary bypass surgery, and choledocholithotomy with T-tube insertion reached 82.3%, 55.2%, and 42.1%, respectively. None of the patients who maintained complete resolution by the last follow-up day developed CCA. In univariate analysis, female, both-sided intrahepatic duct stones, and liver atrophy at any location were associated with increased risk of CCA. Multivariate analysis revealed that both-sided atrophy significantly increased risk of CCA (hazard ratio, 4.56; 95% confidence interval, 1.48 to 14.09; p=0.008). In 21 patients who developed intrahepatic CCA, tumor was located mostly in the atrophied lobe (p=0.023). CONCLUSIONS: In RPC patients, acute cholangitis, liver abscess, cirrhotic complications, and CCA frequently developed. Both-sided liver atrophy was a significant risk factor for developing CCA.
Atrophy ; Cholangiocarcinoma ; Cholangitis ; Cohort Studies ; Diagnosis ; Female ; Fibrosis ; Follow-Up Studies ; Hepatectomy ; Humans ; Liver ; Liver Abscess ; Methods ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Risk Factors ; Seoul

Sclerosing cholangitis (SC) is defined as a condition with progressive stenosis and destruction of the bile ducts due to diffuse inflammation and fibrosis and currently includes three categories: primary sclerosing cholangitis (PSC), secondary cholangitis, and IgG4-related sclerosing cholangitis (IgG4-SC). SC categories share similar clinical features, such as cholestasis. Patients with SC present with cholestatic symptoms, including jaundice and pruritus, and blood tests reveal elevation of cholestatic enzymes. Cholangiography, endoscopic or magnetic, is inevitably required for making a diagnosis. Although the presentation of IgG4-SC and PSC are similar, the comorbidities, treatment response, and outcomes differ significantly, and therefore, it is strongly advisable to be familiar with these two diseases to make a correct diagnosis. Differentiation of cholangiocarcinoma from IgG4-SC and PSC is also extremely important. In this review, the clinical characteristics, comorbidities, treatment and outcomes of IgG4-SC and PSC will be outlined based on experience mainly from Japan.
Bile Ducts ; Cholangiocarcinoma ; Cholangiography ; Cholangitis ; Cholangitis, Sclerosing ; Cholestasis ; Comorbidity ; Constriction, Pathologic ; Diagnosis ; Fibrosis ; Hematologic Tests ; Humans ; Immunoglobulin G ; Inflammation ; Japan ; Jaundice ; Pruritus

Mixed hepatocellular carcinoma and cholangiocarcinoma (HCC-CC) are rare tumors, and the risk factors associated with them are not well understood yet. Moreover, the diagnosis of mixed HCC-CC can be complicated due to the difficulty in distinguishing mixed HCC-CC from HCC and intrahepatic CCC on radiological images. Serum tumor markers are useful when the radiological images are inconclusive. It remains unclear whether the prognosis of mixed HCC-CC differs from that of HCC. However, several studies have reported that the tumor recurrence and patient survival rates of mixed HCC-CC were similar to those of HCC after liver transplantation (LT) and liver resection. In this paper, we report that LT in patients with mixed HCC-CC achieves outcomes which are similar to those seen in LT for HCC. Therefore, the diagnosis of mixed HCC-CC should not be considered as a contraindication for LT.
Biomarkers, Tumor ; Carcinoma, Hepatocellular ; Cholangiocarcinoma ; Diagnosis ; Humans ; Liver Transplantation ; Liver ; Prognosis ; Recurrence ; Risk Factors ; Survival Rate