Incidence Of Intrahepatic Cholangiocarcinoma Research Articles

Multi-Omics Profiling Unveils the Complexity and Dynamics of Immune Infiltrates in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a highly heterogeneous malignancy. The reasons behind the global rise in the incidence of ICC remain unclear, and there exists limited knowledge regarding the immune cells within the tumor microenvironment (TME). In this study, a more comprehensive analysis of multi-omics data was performed using machine learning methods. The study found that the immunoactivity of B cells, macrophages, and T cells in the infiltrating immune cells of ICC exhibits a significantly higher level of immunoactivity in comparison to other immune cells. During the immune sensing and response, the effect of antigen-presenting cells (APCs) such as B cells and macrophages on activating NK cells was weakened, while the effect of activating T cells became stronger. Simultaneously, four distinct subpopulations, namely BLp, MacrophagesLp, BHn, and THn, have been identified from the infiltrating immune cells, and their corresponding immune-related marker genes have been identified. The immune sensing and response model of ICC has been revised and constructed based on our current comprehension. This study not only helps to deepen the understanding the heterogeneity of infiltrating immune cells in ICC, but also may provide valuable insights into the diagnosis, evaluation, treatment, and prognosis of ICC.

HSPB8-BAG3 chaperone complex modulates cell invasion in intrahepatic cholangiocarcinoma by regulating CASA-mediated Filamin A degradation

ABSTRACT The incidence of intrahepatic cholangiocarcinoma (ICC) is steadily rising, and it is associated with a high mortality rate. Clinical samples were collected to detect the expression of HSPB8 and BAG3 in ICC tissues. ICC cells were cultured and transfected with plasmids that overexpressed or silenced specific genes to investigate the impact of gene expression alterations on cell function. qPCR and Western blot techniques were utilized to measure gene and protein expression levels. A wound healing assay was conducted to assess cell migration ability. The Transwell assay was used to assess cell invasion ability. Co-IP was used to verify the binding relationship between HSPB8 and BAG3. The effects of HSPB8 and BAG3 on lung metastasis of tumors in vivo were verified by constructing a metastatic tumor model. Through the above experiments, we discovered that the expressions of HSPB8 and BAG3 were up-regulated in ICC tissues and cells, and their expressions were positively correlated. The metastatic ability of ICC cells could be promoted or inhibited by upregulating or downregulating the expression of BAG3. Furthermore, the HSPB8-BAG3 chaperone complex resulted in the abnormal degradation of Filamin A by activating autophagy. Increased expression of Filamin A inhibits the migration and invasion of ICC cells. Overexpression of HSPB8 and BAG3 in vivo promoted the lung metastasis ability of ICC cells. The HSPB8-BAG3 chaperone complex promotes ICC cell migration and invasion by regulating CASA-mediated degradation of Filamin A, offering insights for enhancing ICC therapeutic strategies.

Incidence and Long-Term Outcomes of Biliary Tract Cancers in Olmsted County, Minnesota from 1976 to 2018.

Biliary tract cancers, including cholangiocarcinoma, gallbladder, and ampulla of Vater cancers, rank second among hepatobiliary cancers, known for their poor prognoses. The United States has witnessed a notable increase in intrahepatic cholangiocarcinoma incidence. This study examines the incidence and survival outcomes of biliary tract cancers in Olmsted County, Minnesota from 1976 to 2018. Using data from the Rochester Epidemiology Project (REP), residents aged 20 and above were analyzed across four eras. Incidence rates were calculated and adjusted for age and sex, and temporal trends were assessed using Poisson regression. Intrahepatic cholangiocarcinoma exhibited a significant escalation in incidence rates over time, while gallbladder cancers showed a decline among women. Median survival times for biliary tract cancers notably improved. These findings confirm the rising incidence of intrahepatic cholangiocarcinoma and suggest improving survival rates. Nevertheless, the overall prognosis for biliary tract cancers remains very poor, emphasizing the continual need for enhanced management strategies and further research.

Prognostic value of FGFR2 alterations in patients with iCCA undergoing surgery or systemic treatments: A meta-analysis.

Over recent years, there has been a notable rise in the incidence of intrahepatic cholangiocarcinoma (iCCA), which presents a significant challenge in treatment due to its complex disease characteristics and prognosis. Notably, the identification of fibroblast growth factor receptor 2 (FGFR2) fusion/rearrangement, a potential oncogenic driver primarily observed in iCCA, raises questions about its impact on the prognostic outcomes of patients undergoing surgical intervention or other therapeutic approaches. A comprehensive search from inception to July 2023 was conducted across PubMed, Embase, Web of Science, and the Cochrane Library databases. The objective was to identify relevant publications comparing the prognosis of FGFR2 alterations and no FGFR2 alterations groups among patients with iCCA undergoing surgical resection or other systemic therapies. The primary outcome indicators, specifically Overall Survival (OS) and Disease-Free Survival (DFS), were estimated using Hazard Ratios (HRs) with 95% confidence intervals (CIs), and statistical significance was defined as p < .05. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Statistical analyses were performed using Review Manager 5.4 software and Stata, version 12.0. Six studies, involving 1314 patients (FGFR2 alterations group n = 173 and no FGFR2 alterations group n = 1141), were included in the meta-analysis. The analysis revealed that the FGFR2 alterations group exhibited a significantly better OS prognosis compared to the no FGFR2 alterations group, with a fixed-effects combined effect size HR = 1.31, 95%CI = 1.001-1.715, p = .049. Furthermore, meta-regression and subgroup analysis showed that the length of the follow-up period did not introduce heterogeneity into the results. This finding indicates the stability and reliability of the study outcomes. The current study provides compelling evidence that FGFR2 alterations are frequently associated with improved survival outcomes for patients with iCCA undergoing surgical resection or other systemic treatments. Additionally, the study suggests that FGFR2 holds promise as a safe and dependable therapeutic target for managing metastatic, locally advanced or unresectable iCCA. This study offers a novel perspective in the realm of targeted therapy for iCCA, presenting a new and innovative approach to its treatment.

Epidemiology, survival and new treatment modalities for intrahepatic cholangiocarcinoma (IHCC).

e16217 Background: Intrahepatic cholangiocarcinoma (IHCC), a rare biliary tract cancer, has been rising in incidence and is associated with poor survival. With the advent of new treatment modalities and various ongoing research, population-based perspective can be helpful to reflect the progress in managing this deadly disease and provide updated outcome information as a reference for comparison during upcoming clinical studies. We would like to provide a 20-year update on incidence and survival with reference to landmark trials, with a focus on survival outcomes of the recent 5 years for future insights. Recent and ongoing clinical trials will be discussed. Methods: This study extracted population data from the Surveillance, Epidemiology, and End Results (SEER) database. Age-adjusted incidence rate (AAIRs) and survival rate (SR) trends were calculated from January 2000 to December 2020 using 22 registries for the US population. Incidence and survival rates were collected from the SEER database, reported per 100,000 population and age adjusted to the 2020 US standard population. The annual percent change (APC) was used to report long term trends. Results: In this analysis of 19,948 IHCC patients, the AAIR increased from 0.49 per 100,000 in 2000 to 1.38 in 2020 (APC 6.94, 95% CI 6.32 to 7.56), with a notable decline from 2019 to 2020. Incidence rates overall displayed an uptrend course across subgroups divided by sex, race, age, and disease stage. The age-adjusted mOS climbed from 5.28 months in 2000 to 9.3 months in 2013, maintaining between 8.0-9.0 months after 2013. Using 2010 as a cutoff, when the ABC-02 trial was published, the decade-based mOS increased from 6.55 in 2000-2010 to 9.06 in 2010-2020, which remained statistically significant at 1-year, 3-year, and 5-year OS. During 2015-2020, the overall mOS was 8.8 months, with mOS of 24.3 months, 12.1 months, and 5.4 months for local, regional, and distant stages, respectively. Conclusions: These results indicate a steady rise in IHCC incidence since 2000, consistent across all subgroups. Survival rates have improved since 2000 but stabilized after 2013, following the publication of the ABC-02 trial published in 2010, which used systemic gemcitabine and cisplatin for unresectable iHCC. Updated survival data from 2015 onwards will serve as a reference of comparison for forthcoming clinical trials.

Incidence trend and prognosis of intrahepatic cholangiocarcinoma: a study based on the SEER database.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer after hepatocellular carcinoma (HCC). ICC and HCC have different cellular origins; therefore, ICC is significantly different from HCC in terms of aetiology, mechanism, tumour biological behaviour, treatment methods, and prognosis. The objective of this study was to investigate the current incidence trend and prognosis of ICC and deepen the understanding of ICC. A large sample of ICC and HCC patient data was obtained from the Surveillance, Epidemiology and End Results (SEER) database of the National Cancer Institute (NCI), USA. The incidence trend, prognosis, and the effect of surgery and lymph node dissection on the prognosis of ICC patients were analysed. In recent years, the incidence of ICC has increased. The treatment effect of ICC patients has been significantly improved. But the prognosis of ICC patients is significantly worse than that of HCC patients. Surgery can benefit all stages of ICC, and lymph node dissection is beneficial for the prognosis of patients with positive lymph nodes (N1). In recent years, the incidence of ICC has been increasing, and its prognosis remains poor, which is a cause for concern. We need to understand the epidemiological and pathophysiological characteristics of ICC and explore more effective treatment methods to improve the efficacy of treatment for ICC patients and prolong their survival.

New epidemiologic trends in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy and the second most frequent primary hepatic malignancy after hepatocellular carcinoma. During the past three decades, the incidence of intrahepatic cholangiocarcinoma (iCCA) has risen in Western Europe, while the incidence of extrahepatic cholangiocarcinoma (eCCA) has remained stable or fallen. The mortality rates of iCCA, which are greater than those of eCCA, showed also an increasing trend, while those of eCCA remained stable. Well-known risk factors like hepatobiliary flukes, hepatolithiasis and choledochal cysts are important in the development of iCCA particularly in Asian countries. In Western countries, the primary sclerosing cholangitis is the most common risk factor for CCA. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and cirrhosis are considered to be risk factors for iCCA. Emergent risk factors such as obesity, diabetes and MAFLD are increasingly associated mostly with iCCA.

Nomogram based on Sonazoid contrast-enhanced ultrasound to differentiate intrahepatic cholangiocarcinoma and poorly differentiated hepatocellular carcinoma: a prospective multicenter study.

The aim of this study was to develop a predictive model based on Sonazoid contrast-enhanced ultrasound (SCEUS) and clinical features to discriminate poorly differentiated hepatocellular carcinoma (P-HCC) from intrahepatic cholangiocarcinoma (ICC). Forty-one ICC and forty-nine P-HCC patients were enrolled in this study. The CEUS LI-RADS category was assigned according to CEUS LI-RADS version 2017. Based on SCEUS and clinical features, a predicated model was established. Multivariate logistic regression analysis and LASSO logistic regression were used to identify the most valuable features, 400 times repeated 3-fold cross-validation was performed on the nomogram model and the model performance was determined by its discrimination, calibration, and clinical usefulness. Multivariate logistic regression and LASSO logistic regression indicated that age (>51 y), viral hepatitis (No), AFP level (≤ 20 µg/L), washout time (≤ 45 s), and enhancement level in the Kupffer phase (Defect) were valuable predictors related to ICC. The area under the receiver operating characteristic (AUC) of the nomogram was 0.930 (95% CI: 0.856-0.973), much higher than the subjective assessment by the sonographers and CEUS LI-RADS categories. The calibration curve showed that the predicted incidence was more consistent with the actual incidence of ICC, and 400 times repeated 3-fold cross-validation revealed good discrimination with a mean AUC of 0.851. Decision curve analysis showed that the nomogram could increase the net benefit for patients. The nomogram based on SCEUS and clinical features can effectively differentiate P-HCC from ICC.

Hepatocellular carcinoma and intrahepatic cholangiocarcinoma incidence between 2006 and 2015 in China: estimates based on data from 188 population-based cancer registries.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common subtypes of primary liver cancer, but nationwide incidence of both liver cancer subtypes have never been reported in China. We aimed to estimate the most recent incidence of HCC and ICC and temporal trends in China based on the most updated data from high qualified population-based cancer registries (covering 13.1% of the national population), in comparison to those in the United States at the same period. We used data from 188 Chinese population-based cancer registries covering 180.6 million population of China to estimate the nationwide incidence of HCC and ICC in 2015. And 22 population-based cancer registries' data were used to estimate the trends of HCC and ICC incidence from 2006 to 2015. Multiple imputation by chained equations method was used to impute liver cancer cases with unknown subtype (50.8%). We used data from 18 population-based registries from the Surveillance, Epidemiology, and End Results program to analyze incidence of HCC and ICC in the United States. In China, an estimated 301,500 and 61,900 newly diagnosed HCC and ICC occurred in 2015. The overall age-standardized rates (ASRs) of HCC incidence decreased by 3.9% per year. For ICC incidence, the overall ASR was relatively stable, but increased in the population of over 65 years old. Subgroup analysis by age showed that the ASR of HCC incidence had the sharpest decline in population who were less than 14 years old and received neonatally hepatitis B virus (HBV) vaccination. In the United States, though the incidence of HCC and ICC were lower than those in China, the overall HCC and ICC incidence increased by 3.3% and 9.2% per year. China still faces with a heavy burden of liver cancer incidence. Our results may further support the beneficial effect of Hepatitis B vaccination on reduction of HCC incidence. Both healthy lifestyle promotion and infection control are needed for future liver cancer control and prevention for China and the United States.

Time-trends in liver cancer incidence and mortality rates in the U.S. from 1975 to 2017: a study based on the Surveillance, Epidemiology, and End Results database.

A previous study has examined the overall cancer statistics. However, more detailed statistics regarding liver cancer have not been provided. We evaluated the incidence and mortality trends of liver and intrahepatic bile duct cancer in the United States from 1975 to 2017 based on the data in the Surveillance, Epidemiology, and End Results (SEER) database. Age, gender, race, metastasis, tumor site, and tumor grade of patients were extracted from the SEER database. Codes C22.0 and C22.1 of the International Classification of Disease for Oncology were applied to identify patients with hepatocellular carcinoma (HCC) and/or intrahepatic cholangiocarcinoma (ICC). Age-specified incidence, age-standardized incidence and mortality, 5-year relative survival, race-specific accumulative incidence and mortality, and geographic-specific accumulative mortality were calculated in different groups. Changes in trends of liver cancer incidence and mortality were assessed using Joinpoint regression. The overall incidence increased significantly from 2.641/100,000 person-years in 1975 to 8.657/100,000 person-years in 2017 [average annual percent change (AAPC) =3.42, 95% confidence interval (CI): 3.28-3.62, P<0.001]. The steepest incidence rate increase was observed in the 60-69-year-old age group (AAPC =4.40, 95% CI: 4.10-4.70, P<0.001). Males exhibited a more rapid increase in cancer incidence, from 3.928/100,000 to 13.128/100,000 person-years (AAPC =3.41, 95% CI: 3.21-3.61, P<0.001), than females [from 1.642/100,000 to 4.783/100,000 person-years (AAPC =3.03, 95% CI: 2.91-3.21, P=0.001)]. The overall mortality rate increased from 2.808/100,000 person-years in 1975 to 6.648/100,000 person-years in 2017 (AAPC =2.41, 95% CI: 2.29-2.51, P<0.001). The highest mortality rate was observed in Hawaii (6.996/100,000 person-years). The incidence and mortality rates of HCC and ICC increased from 1975 to 2017, especially in males, non-Hispanic Blacks and older individuals. Comprehensive policy and control measures should be implemented to reduce the burden of disease, particularly through health monitoring and intervention for high-risk groups.

Proteomic and single-cell landscape reveals novel pathogenic mechanisms of HBV-infected intrahepatic cholangiocarcinoma

Despite the epidemiological association between intrahepatic cholangiocarcinoma (ICC) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic effects. A cohort of 32 HBV-infected ICC and 89 non-HBV-ICC patients were characterized using whole-exome sequencing, proteomic analysis, and single-cell RNA sequencing. Proteomic analysis revealed decreased cell-cell junction levels in HBV-ICC patients. The cell-cell junction level had an inverse relationship with the epithelial-mesenchymal transition (EMT) program in ICC patients. Analysis of the immune landscape found that more CD8 Tcells and Th2 cells were present in HBV-ICC patients. Single-cell analysis indicated that transforming growth factor beta signaling-related EMT program changes increased in tumor cells of HBV-ICC patients. Moreover, ICAM1+ tumor-associated macrophages are correlated with a poor prognosis and contributed to the EMT in HBV-ICC patients. Our findings provide new insights into the behavior of HBV-infected ICC driven by various pathogenic mechanisms involving decreased cell junction levels and increased progression of the EMT program.

Minimally invasive approaches to intrahepatic cholangiocarcinoma

While the incidence of intrahepatic cholangiocarcinoma (ICC) is increasing, few patients are surgical candidates, and recurrence rates remain high. Surgical resection remains the only potential curative therapy for ICC, and many retrospective cohorts have demonstrated comparable short-term and long-term outcomes between open, laparoscopic, and robotic liver resection (RLR) for ICC. However, rates of lymphadenectomy remain low amongst all groups, especially in laparoscopic approaches, despite its role in prognostication and therapeutic management. RLR may offer many of the short-term benefits of laparoscopic liver resection (LLR) and facilitate adequate lymphadenectomy while also increasing the ability to access posterosuperior segments and perform major hepatectomies.

Fucosyltransferase 5 Promotes the Proliferative and Migratory Properties of Intrahepatic Cholangiocarcinoma Cells via Regulating Protein Glycosylation Profiles

Background: The incidence of intrahepatic cholangiocarcinoma (ICC) is increasing globally, and its prognosis has not improved substantially in recent years. Understanding the pathogenesis of ICC may provide a theoretical basis for its treatment. In this study, we investigated the effects and underlying mechanisms of fucosyltransferase 5 (FUT5) on the malignant progression of ICC. Methods: FUT5 expression in ICC samples and adjacent nontumor tissues was compared using quantitative real-time polymerase chain reaction and immunohistochemical assays. We performed cell counting kit-8, colony formation, and migration assays to determine whether FUT5 influenced the proliferation and mobility of ICC cells. Finally, mass spectrometry was performed to identify the glycoproteins regulated by FUT5. Results: FUT5 mRNA was significantly upregulated in most ICC samples compared with corresponding adjacent nontumor tissues. The ectopic expression of FUT5 promoted the proliferation and migration of ICC cells, whereas FUT5 knockdown significantly suppressed these cellular properties. Mechanistically, we demonstrated that FUT5 is essential for the synthesis and glycosylation of several proteins, including versican, β3 integrin, and cystatin 7, which may serve key roles in the precancer effects of FUT5. Conclusions: FUT5 is upregulated in ICC and promotes ICC development by promoting glycosylation of several proteins. Therefore, FUT5 may serve as a therapeutic target for the treatment of ICC.

S45 Trends in the Incidence of Intrahepatic Cholangiocarcinoma Between 1990 and 2019 Stratified by Race, Ethnicity and Gender Among Pennsylvania Residents

S45 Trends in the Incidence of Intrahepatic Cholangiocarcinoma Between 1990 and 2019 Stratified by Race, Ethnicity and Gender Among Pennsylvania Residents

Secular trends of intrahepatic cholangiocarcinoma in a high endemic area: A population-based study.

BACKGROUNDIntrahepatic cholangiocarcinoma (ICC) is one of the most aggressive malignancies. However, because of its scarcity there are limited population-based data available for investigations into its epidemiologic characteristics. In Taiwan, we have a national cancer registry database that can be used to evaluate the secular trends of ICC.AIMTo evaluate secular trends of ICC according to age, sex, and risk factors in Taiwan.METHODSIn this population-based study, we used the national Taiwan Cancer Registry database. Age-standardized and relative percent changes in incidence rates were used to describe secular trends in incidence rates and sex ratios of ICC in Taiwan.RESULTSThe age-standardized ICC incidence rate among males increased from 1.51 per 100000 in 1993-1997 to 4.07 per 100000 in 2013-2017 and among female from 1.73 per 100000 to 2.95 per 100000. The incidence in females tended to plateau after 2008-2012. For males, the ICC incidence increased as age increased. In the long-term incidence trend of ICC in females, the incidence of the four age groups (40-44, 45-49, 50-54 and 55-59 years) remained stable in different years; although, the incidence of the 60-64 group had a peak in 2003-2007, and the peak incidence of the 65-69 and 70-74 groups occurred in 2008-2012. Among males, beginning at the age of 65, there were increases in the incidence of ICC for the period of 2003-2017 as compared with females in the period of 2003-2017.CONCLUSIONIncreased incidence of ICC occurred in Taiwan over the past two decades. The increased incidence has progressively shifted toward younger people for both males and females.

Review of Mass-Forming Intrahepatic Cholangiocarcinoma

The incidence of intrahepatic cholangiocarcinoma (iCCA) is highest in Eastern countries, such as Thailand, South Korea, and China, but its incidence and mortality are increasing worldwide. Over recent decades, the worldwide age-standardized incidence for iCCA has been steadily increasing, whereas that for perihilar CCA and distal CCA has been decreasing. The macroscopic growth pattern of CCA is somewhat different according to the anatomic location of the tumor. iCCA can show three main patterns of growth: mass forming, periductal infiltrating, and intraductal growing. Morphologic classification is important to understand the mode of tumor spread, which is critical in predicting a tumor’s resectability and in planning the extent of surgery. Furthermore, different macroscopic growth types are resulting in different imaging findings and different list of differential diagnosis. This review provides a comprehensive and critical overview of current knowledge and what is envisaged on the horizon for iCCA, focusing on mas-forming type. 1. Tumor growth pattern 2. Histological subtype of iCCA 3. Imaging phenotype and differential diagnosis of iCCA 4. Staging of iCCA 5. Preoperative prognostic prediction of iCCA

Changing incidence and survival of intrahepatic cholangiocarcinoma based on Surveillance, Epidemiology, and End Results Database (2000-2017).

Backgrounds/AimsHistorically, the incidence and prognosis of patients diagnosed with intrahepatic cholangiocarcinoma (ICC) have been inadequately understood. Survival analysis in ICC has yet to be investigated in a population-based study.MethodsWe conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program (SEER) 18 Registry. Risk ratios were estimated via Poisson regression. Hazard ratios for 5-year survival were estimated using hierarchical Cox regression models.ResultsMales show a higher rate of age-adjusted ICC incidence. Blacks carried a decreased risk of ICC diagnosis than Whites, while Asians revealed a higher risk of ICC diagnosis when compared with Whites. The observed survival rates at 12, 36, and 60 months were 36.3%, 12.8%, and 8.1%, respectively. Compared with Whites, Blacks showed an increased risk of death (p < 0.01). Lymph node resection during surgery was associated with a 64.1% reduced risk of mortality (p < 0.01). A higher T stage at diagnosis was associated with poor survival (p < 0.01). Surgery combined with chemoradiotherapy, radiotherapy, or chemotherapy was associated with a reduced risk of mortality compared with nonsurgical interventions (p < 0.01).ConclusionsICC incidence has been increasing since 2000, especially in White males. The risk of ICC rises with age. Lymph node removal is associated with better survival. In recent years, survival had worsened, and surgical intervention improved survival compared with nonsurgical management.

The role of Tripartite motif containing 59 (TRIM59) in the proliferation and prognosis of intrahepatic cholangiocarcinoma

Tripartite motif containing 59 (TRIM59) is a crucial gene that is involved in the process of various types of cancer，including breast cancer, lung cancer, colorectal cancer,and so on. Its abnormal expression can affect tumor cell proliferation, metastasis, or apoptosis. In liver cancer, the incidence of intrahepatic cholangiocarcinoma (ICC) is increasing. However, However, it has not been clearly reported on TRIM59 affects the progress of intrahepatic cholangiocarcinoma cells.Firstly, we review the expression of TRIM59 in different cancers and the corresponding normal tissues，and the results preliminarily showed that TRIM59 may be abnormally expressed in many cancers. The author focuses on whether TRIM59 plays a crucial biological role in intrahepatic cholangiocarcinoma. Therefore, we have confirmed through online websites that TRIM59 is highly expressed in intrahepatic cholangiocarcinoma tissues. Furthermore we further found that TRIM59 can be used as an effective prognostic marker for the prognostic guidance of patient survival time. Next, we explore whether the expression level of TRIM59 in intrahepatic cholangiocarcinoma is related to proliferation through the CCK-8 and EDU assay in two ICC cell lines. To further explore how TRIM59 affected the molecular mechanism involved in intrahepatic cholangiocarcinoma cell growth, we found that STAT3 promotes TRIM59 transcription and TRIM59 can affect tumor progression by regulating the PI3K/AKT signaling pathway through luciferase reporter assay and Western blot experiments. In summary, we first found that TRIM59 has great research value in ICC through bioinformatic analysis, then its expression level is closely related to the prognosis through the analysis of clinicopathological indicators of patients with ICC, and the biological mechanism of TRIM59 in ICC provides precise research or therapeutic targets for future cancer treatment. The findings improve our understanding of the potential of TRIM59 in biological functions in ICC and may hold promise as markers for the diagnosis,treatment, and prognosis of ICC. Data availabilityThe raw data of this study are derived from the TCGA database, which are publicly available databases.

Predictive factors for subsequent intrahepatic cholangiocarcinoma associated with hepatolithiasis: Japanese National Cohort Study for 18 years.

Predictive factors for intrahepatic cholangiocarcinoma in long-term follow-up of hepatolithiasis are unknown. We thus conducted a cohort study to investigate the predictive factors for developing intrahepatic cholangiocarcinoma in hepatolithiasis. This cohort is comprised of 401 patients registered in a nationwide survey of hepatolithiasis for 18years of follow-up. Cox regression analysis was used to elucidate predictive factors for developing intrahepatic cholangiocarcinoma. The median follow-up period of patients was 134months. Twenty-two patients developed intrahepatic cholangiocarcinoma and all died. Identified independent significant factors were as follows: age 63years or older (hazard ratio [HR] 3.344), residual stones at the end of treatment (HR 2.445), and biliary stricture during follow-up (HR 4.350). The incidence of intrahepatic cholangiocarcinoma in patients with three factors was significantly higher than that in patients with one or two factors. The incidence in the groups with one or two predictive factors was not different. In 88.9% of patients with both biliary stricture and intrahepatic cholangiocarcinoma, the duration between the diagnoses of biliary stricture and intrahepatic cholangiocarcinoma was ≥ 5years. However, once intrahepatic cholangiocarcinoma developed, 77.8% of patients died within 1 year. Of 24 patients with no symptoms, no previous choledocoenterostomy, no signs of malignancy, no biliary stricture, and no treatment for hepatolithiasis during follow-up, only one developed intrahepatic cholangiocarcinoma. Regarding carcinogenesis, complete stone clearance and releasing biliary stricture can prevent the development of intrahepatic cholangiocarcinoma and improve the prognosis of hepatolithiasis.

First-line chemotherapy plus immunotherapy in biliary tract cancer

Biliary tract cancers have the second highest primary liver tumour incidence after hepatocellular carcinoma.1 They are classified into three subtypes (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma) on the basis of anatomical location, with specific epidemiological, molecular, and therapeutic features.1 The incidence of intrahepatic cholangiocarcinoma is increasing, particularly in high-income countries, in relation to improvement in the differential diagnosis of hepatocellular carcinoma and liver metastases from other adenocarcinomas, and the rising rates of obesity, diabetes, and alcohol use.